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GABA and endocrine regulation relation to neurologic-psychiatric disorders
Neurochem. Int. Vol. 6, No. 1, pp. 23-26, 1984
01974)186/84 $3.00+0.00 Copyright © 1984 Pergamon Press Ltd
Printed in Great Britain. All rights reserved
CRITIQUE GABA AND ENDOCRINE REGULATION--RELATION NEUROLOGIC-PSYCHIATRIC DISORDERS
TO
Y. YONDEAand K. KURIYAMA* Department of Pharmacology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-Ku, Kyoto 602, Japan
Since the discovery of 7-aminobutyric acid (GABA) in the mammalian central nervous system (CNS) in 1950 (Awapara et al., 1950; Roberts and Frankel, 1950; Udenfriend, 1950), various studies for elucidating the functional roles of GABA in the CNS have been carried out, and it seems to be established that GABA is an inhibitory neurotransmitter in the nervous tissues of invertebrate as well as vertebrate (Roberts et al., 1976). In mammals, GABA is present exclusively in the CNS and retina, but not in peripheral nerves (Roberts et al., 1958). It has been demonstrated that GABA resides predominantly in the grey matter; GABA is localized in the dorsal horn in the spinal cord, while white matter and nerve roots have little GABA (Graham et al., 1967; Miyata and Otsuka, 1972). In the substantia nigra which has the highest level of GABA in the brain (Fahn and c r t r , 1968), GABA is concentrated in the pars reticulata (Kanazawa et al., 1973) which has tremendous amounts of nerve terminals from the inhibitory striato-nigral GABAergic pathway (Grofov/t and Rinvik, 1970; Yoshida and Precht, 1971). In addition, the activity of L-glutamic acid decarboxylase (GAD), which catalyzes the alphadecarboxylation of L-glutamic acid to yield GABA, is detected preferentially in the central structures with high concentration of GABA. Studies using microdissection technique have revealed that the microdistribution of GAD well coincides with that of GABA in the cerebellum (Kuriyama et al., 1966), retina (Kuriyama et al., 1968), hippocampus (Okada and Shimada, 1975), hypothalamus (Kimura and Kuriyama, 1975), spinal cord (Yoneda and Kuriyama, 1978) and thalamus (Kuriyama and Yoneda, 1978). Immunocytochemical investigations using the antibody to GAD not only confirmed above findings, but also demonstrated that GAD was localized in
synaptic nerve terminals (McLaughlin et al., 1974; McLaughlin et al., 1975). On the other hand, as Dr DeFeudis quoted, it has been demonstrated that a peripheral tissue has the active metabolic system for GABA. Surprisingly, it was not a nervous tissue, but an endocrine tissue such as pancreatic Langerhans islets (Okada et al., 1976). The islets have a high level of endogenous GABA as well as high activity of GAD, both of which are almost equal to those in the brain. In addition, cancellation of the islets resulted in a significant elevation of the endogenous level of insulin in the pancreas with a concomitant facilitation of the metabolism of GABA (Okada et al., 1976). These findings raised the question whether or not GABA was indeed involved in the function of this endocrine organ. Evidences which suggest possible physiological roles of GABA in the maintenance and/or regulation of the function of various endocrine systems have been now accumulated as reviewed by Dr DeFeudis. For example, there exists noticeable amount of GABA in the hypophysis (Racagni et al., 1979, and GABA has an inhibitory action on the secretion of prolactin (PRL) from the adenohypophysis (Schally et al., 1977; Rivier and Vale, 1977; Racagni et al., 1979). GABA also exerts initial stimulatory effect on the secretion of melanocytestimulating hormone (MSH) from the dispersed cells of the pars intermedia of the hypophysis, followed by the inhibition of the release (Tomiko et al., 1983). Furthermore, GABA elicits a suppressive action on the potassium-stimulated secretion of MSH from the cells (Tomiko et al., 1983). These observations all seem to support the proposal that GABA may play an important regulatory role in the secretory function of the endocrine organ, pituitary. It should be mentioned, however, that the endogenous level of GABA is considerably low in the adenohypophysis which secretes such hormones.
*To whom correspondence should be addressed. 23
24
Y. YONEDAand K. KURIYAMA
GABA is preferentially located in the neurohypophysis (Racagni et al., 1979). Similarly, the adenohypophysi~, has no activity of G A D which catalyzes the formation of GABA despite the occurrence of its degrading enzyme (Racagni et al., 1979), as described in the review of Dr DeFeudis. These results make it reasonable to assume that GABA may modulate the secretion of anterior pituitary hormones through eliciting its non-neurotransmitter action. Similar mysteriousness is seen in other endocrine organs including rat ovary. This organ is reported to have a high affinity uptake system for GABA (Erd6, 1983), GABA receptor binding sites with high affinity (Erd6 and Lapis, 1982), and the activity of G A D (Schaeffer and Hsueh, 1982) as discussed by Dr DeFeudis. In contrast, it has been demonstrated that the presence of high levels of GABA in the rat ovary is attributable to the contamination with the oviduct tissue which contains GABA over 2.5 times the amount present in the whole brain (del Rio, 1981). The existence of higher levels of GABA in the rat oviduct than those in the brain has been confirmed (Erd6, Rosdy and Szporny, 1982). It has been also shown that the endogenous levels of GABA in the oviduct vary during the ovarian cycle (del Rio, 1980). These findings again raise the question; what is the functional significance of GABA in the endocrine organs? Does endogenous GABA modulate the secretion of various hormones through exerting an inhibitory neurotransmitter action or by eliciting a significant action other than a neurotransmitter? If the former is the case, it should be demonstrated that the endocrine organ has GABAergic innervations. Criteria for the identification of a neurotransmitter should be, at least, satisfied in the endocrine tissues. If the latter is the case, it is conceivable that GABA may exhibit a general action on the mechanism of excitation-secretion coupling which in turn results in the alteration of membrane excitability in the excitable tissues such as brain and endocrine organ. It has been demonstrated that the structurally-related compound, taurine, induces an alteration of the release of various neurotransmitters through the interaction with intracellular free Ca -~ available for the release (Kuriyama et al., 1978; Kuriyama, 1980). In contrast, it has been well established that environmental alterations affect the endocrine as well as nervous systems in addition to inducing various neuropsychiatric symptoms. For instance, a stressful manipulation produces various behavioral changes in laboratory animals including the depressive psychosis (Sherman et al., 1979) with a concomitant stimu-
lation of the hypothalamo-pituitary-adrenal axis (Fujiide and Hiroshige, 1978; DeTurck and Vogel, 1982). Application of a stressor also results in a significant alteration in the metabolism and/or the function of other putative neurotransmitters in the central and peripheral nervous systems such as epinephrine, norepinephrine, dopamine and 5-hydroxytryptamine (Thierry et al., 1968; Kvetnansky et al., 1977; McCarty and Kopin, 1978). Recently, it has been shown that a stressful circumstance induces a significant alteration of GABA metabolism in the striatum and hypothalamus without affecting that in other central structures (Yoneda et al., 1983). Considering these findings together with the fact that GABA indeed modulates the secretion of various hormones from the pituitary (for details, see the review by Dr DeFeudis), it seems reasonable to assume that GABA may be involved in the occurrence of various behavioral changes including neuropsychiatric disturbance through the interaction with endocrine systems. CONCLUSION
Accumulating evidence has indicated that GABA is indeed present in various peripheral tissues including endocrine organs in addition to the CNS. Although it is clear that GABA plays an inhibitory neurotransmitter role in the CNS, little has been clarified with regard to the functional significance of this amino acid in the peripheral tissues. Several lines of evidence suggest a possible modulatory action of GABA on the secretion of hormones from various endocrine organs as reviewed by Dr DeFeudis. The exact molecular mechanism underlying these phenomena as well as the origin of this peripheral GABA, however, remain to be elucidated. Since there is no doubt that GABA has a metabolic significance as an intermediate of the Krebs cycle even in the CNS, it seems possible that the peripheral GABA may merely reflect the metabolic activity of the " G A B A shunt" in the tissue. Therefore, one of the urgent problems to be solved in the future studies is the demonstration of the presence of metabolic pathway for the biosynthesis as well as degradation of GABA in the peripheral tissues including endocrine organs. Since it has been postulated that there may exist some compartments of GABA and/or of its metabolic precursor, L-glutamic acid, in the brain, studies on the clarification of compartmentation of GABA are also essential for concluding the functional significance of this amino acid in the secretion of hormones. Elucidation of such problems will automatically give us a clue for the understanding
Critique of the relationship between G A B A , h o r m o n e s a n d neuropsychiatric disorders.
REFERENCES
Awapara J., Landua A. J., Fuerst R. and Scale B. (1950). Free y-aminobutyric acid in brain. J. biol. Chem. 187, 35-39. del Rio R. M. (1981). y-Aminobutyric acid system in rat oviduct. J. biol. Chem. 256, 9816-9819. DeTurck K. H. and Vogel W. H. (1982). Effect of acute ethanol on plasma and brain catecholamine levels in stressed and unstressed rats: Evidence for an ethanolstress interaction. J. Pharmac. exp. Ther. 223, 348-354. Erd6 S. L. and Lapis E. (1982). Bicuculline sensitive GABA receptors in rat ovary. Eur. J. Pharmac. 85, 243-246. Erd6 S. L., Rosdy B. and Szporny L. (1982). Higher GABA concentrations in Fallopian tube than in brain of the rat. J. Neurochem. 38, 1174-1176. Erd6 S. L. (1983). High affinity, sodium-depdendent y-aminobutyric acid uptake by slices of rat ovary. J. Neurochem. 40, 582-584. Fahn S. and Crt6 L. J. (1968). Regional distribution of gamma-aminobutyric acid (GABA) in brain of the rhesus monkey. J. Neurochem. 15, 209-213. Fujiide K. and Hiroshige T. (1978). Changes in rat hypothalamic content of corticotrophin-releasing factor (CRF) activity, plasma ACTH and corticosterone under stress and the effect of cycloheximide. Acta endocr., Copenh. 89, 10-19. Graham L. T. Jr, Shank R. P., Werman R. and Aprison M. H. (1967). Distribution of some synaptic transmitter suspects in cat spinal cord: Glutamic acid, aspartic acid, Gamma-aminobutyric acid, glycine, and glutamine. J. Neurochem. 14, 465~,72. Grofov~ I. and Rinvik E. (1970). An experimental electron microscopic study on the striatonigral projection in the cat. Exp. Brain Res. l l , 249-262. Kanazawa I., Miyata Y., Toyokura Y. and Otsuka M. (1973). The distribution of gamma-aminobutyric acid (GABA) in the human substantia nigra. Brain Res. 51, 363-365. Kimura H. and Kuriyama K. (1975). Distribution of gamma-aminobutyric acid (GABA) in the rat hypothalamus: Functional correlates of GABA with activities of appetite controlling mechanisms. J. Neurochem. 24, 903-907. Kuriyama K., Haber B., Sisken B. and Roberts E. (1966). The ~/-aminobutyric acid system in rabbit cerebellum. Proc. natn. acad. Sci., U.S.A. 55, 846-852. Kuriyama K., Siskin B., Haber B. and Roberts E. (1968). The y-aminobutyric acid system in rabbit retina. Brain Res. 9, 165-168. Kuriyama K. and Yoneda Y. (1978). Morphine-induced alterations of 7-aminobutyric acid and taurine contents and L-glutamate decarboxylase activity in rat spinal cord and thalamus: Possible correlates with analgesic action of morphine. Brain Res. 148, 163-179. Kuriyama K., Muramatsu M., Nakagawa K. and Kakita K. (1978). Modulating role of taurine on release of neurotransmitters and calcium transport in excitable tissues. In: Taurine and Neurological Disorders (Barbeau A. and
25
Huxtable R. J., eds), pp. 201-216. Raven Press, New York. Kuriyama K. (1980). Taurine as a neuromodulator. Fedn Proc. 39, 2680-2684. Kvetnansky R., Sun C. L., Torda T. and Kopin I. J. (1977). Plasma epinephrine and norepinephrine levels in stressed rats. Effect of adrenalectomy. Pharmacologist 19, 241-251. McCarty R. and Kopin I. J. (1978). Sympatho-adrenal medullary activity and behavior during exposure to footshock stress: a comparison of seven rat strains. Physiol. Behav. 21, 567-572. McLaughlin B. J., Wood J. G., Saito K., Barber R., Vaughn J. E., Roberts E. and Wu J.-Y. (1974). The fine structural localization of glutamate decarboxylase in synaptic terminals of rodent cerebellum. Brain Res. 76, 377-391. McLaughlin B. J., Wood J. G., Saito K., Roberts E. and Wu J.-Y. (1975). The fine structural localization of glutamate decarboxylase in developing axonal processes and presynaptic terminals of cerebellum. Brain Res. 85, 355-371. Miyata Y. and Otsuka M. (1972). Distribution of ~-aminobutyric acid in cat spinal cord and the alteration produced by local ischaemia. J. Neurochem. 19, 1833-1834. Okada Y. and Shimada C. (1975). Distribution of 7-aminobutyric acid (GABA) and glutamate decarboxylase activity in the guinea-pig hippocampus-microassay method for the determination of GAD activity. Brain Res. 98, 202-206. Okada Y., Taniguchi H. and Shimada C. (1976), High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. Science 194, 620-622. Racagni G., Apud J. A., Locatelli V., Cocchi D., Nistico G., Di Giorgio R. M. and Mfiller E. E. (1979). GABA of CNS origin in the rat anterior pituitary inhibits prolactin secretion. Nature 281, 575-578. Rivier C. and Vale W. (1977). Effects of 7-aminobutyric acid and histamine on prolactin secretion in the rat. Endocrinology 101, 506-511. Roberts E. and Frankel S. (1950). ~,-Aminobutyric acid in brain: Its formation from glutamic acid. J. biol. Chem. 187, 55-63. Roberts E., Lowe I. P., Guth L. and Jelinek B. (1958). Distribution of gamma-aminobutyric acid and other amino acids in nervous tissue of various species. J. exp. Zool. 138, 313-328. Roberts E., Chase T. N. and Tower D. B. (1976). GABA in Nervous System Function, Raven Press, New York. Schaeffer J. M. and Hsueh A. J. W. (1982). Identification of gamma-aminobutyric acid and its binding sites in the rat ovary. Life Sci. 30, 1599-1604. Shally A. V., Redding T. W., Arimura A., Dupont A. and Linthicum G. L. (1977). Isolation of 7-aminobutyric acid from pig hypothalami and demonstration of its prolactin release-inhibiting (PIF) activity in vivo and in vitro. Endocrinology 100, 681-691. Sherman A. D., Allers G. L., Petty F. and Henn F. A. (1979). A neuropharmacologically-relevant animal model of depression. Neuropharmacology 18, 891-893. Thierry A. M., Javoy F., Glowinski J. and Kety S. S. (1968). Effect of stress on the metabolism of norepinephrine, dopamine and serotonin in the central nervous system of the rat. I. Modification of norepinephrine turnover. J. Pharmac. exp. Ther. 163, 163-172.
26
Y. YONEDA and K. KURIYAMA
Tomiko S. A., Taraskevick P. S. and Douglas W. W. (1983). GABA acts directly on cells of pituitary pars intermedia to alter hormone output. Nature 301, 706-707. Udenfriend S. (1950). Identification of ),-aminobutyric acid in brain by the isotope derivative method. J. biol. Chem. 187, 65-69. Yoneda Y. and Kuriyama K. (1978). A comparison of microdistributions of taurine and cysteine sulphinate decarboxylatse activity with those of GABA and L-
glutamate decarboxylase activity in rat spinal cord and thalamus. J. Neurochem. 30, 821-825. Yoneda Y., Kanmori K., Ida S. and Kuriyama K. (1983). Stress-induced alterations in metabolism of v-aminobutyric acid in rat brain. J. Neurochem. 40, 350-356. Yoshida M. and Precht W. (197 l). Monosynaptic inhibition of neurons of the substantia nigra by caudo-nigral fibers. Brain Res. 32, 225-228.
01974)186/84 $3.00+0.00 Copyright © 1984 Pergamon Press Ltd
Printed in Great Britain. All rights reserved
CRITIQUE GABA AND ENDOCRINE REGULATION--RELATION NEUROLOGIC-PSYCHIATRIC DISORDERS
TO
Y. YONDEAand K. KURIYAMA* Department of Pharmacology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-Ku, Kyoto 602, Japan
Since the discovery of 7-aminobutyric acid (GABA) in the mammalian central nervous system (CNS) in 1950 (Awapara et al., 1950; Roberts and Frankel, 1950; Udenfriend, 1950), various studies for elucidating the functional roles of GABA in the CNS have been carried out, and it seems to be established that GABA is an inhibitory neurotransmitter in the nervous tissues of invertebrate as well as vertebrate (Roberts et al., 1976). In mammals, GABA is present exclusively in the CNS and retina, but not in peripheral nerves (Roberts et al., 1958). It has been demonstrated that GABA resides predominantly in the grey matter; GABA is localized in the dorsal horn in the spinal cord, while white matter and nerve roots have little GABA (Graham et al., 1967; Miyata and Otsuka, 1972). In the substantia nigra which has the highest level of GABA in the brain (Fahn and c r t r , 1968), GABA is concentrated in the pars reticulata (Kanazawa et al., 1973) which has tremendous amounts of nerve terminals from the inhibitory striato-nigral GABAergic pathway (Grofov/t and Rinvik, 1970; Yoshida and Precht, 1971). In addition, the activity of L-glutamic acid decarboxylase (GAD), which catalyzes the alphadecarboxylation of L-glutamic acid to yield GABA, is detected preferentially in the central structures with high concentration of GABA. Studies using microdissection technique have revealed that the microdistribution of GAD well coincides with that of GABA in the cerebellum (Kuriyama et al., 1966), retina (Kuriyama et al., 1968), hippocampus (Okada and Shimada, 1975), hypothalamus (Kimura and Kuriyama, 1975), spinal cord (Yoneda and Kuriyama, 1978) and thalamus (Kuriyama and Yoneda, 1978). Immunocytochemical investigations using the antibody to GAD not only confirmed above findings, but also demonstrated that GAD was localized in
synaptic nerve terminals (McLaughlin et al., 1974; McLaughlin et al., 1975). On the other hand, as Dr DeFeudis quoted, it has been demonstrated that a peripheral tissue has the active metabolic system for GABA. Surprisingly, it was not a nervous tissue, but an endocrine tissue such as pancreatic Langerhans islets (Okada et al., 1976). The islets have a high level of endogenous GABA as well as high activity of GAD, both of which are almost equal to those in the brain. In addition, cancellation of the islets resulted in a significant elevation of the endogenous level of insulin in the pancreas with a concomitant facilitation of the metabolism of GABA (Okada et al., 1976). These findings raised the question whether or not GABA was indeed involved in the function of this endocrine organ. Evidences which suggest possible physiological roles of GABA in the maintenance and/or regulation of the function of various endocrine systems have been now accumulated as reviewed by Dr DeFeudis. For example, there exists noticeable amount of GABA in the hypophysis (Racagni et al., 1979, and GABA has an inhibitory action on the secretion of prolactin (PRL) from the adenohypophysis (Schally et al., 1977; Rivier and Vale, 1977; Racagni et al., 1979). GABA also exerts initial stimulatory effect on the secretion of melanocytestimulating hormone (MSH) from the dispersed cells of the pars intermedia of the hypophysis, followed by the inhibition of the release (Tomiko et al., 1983). Furthermore, GABA elicits a suppressive action on the potassium-stimulated secretion of MSH from the cells (Tomiko et al., 1983). These observations all seem to support the proposal that GABA may play an important regulatory role in the secretory function of the endocrine organ, pituitary. It should be mentioned, however, that the endogenous level of GABA is considerably low in the adenohypophysis which secretes such hormones.
*To whom correspondence should be addressed. 23
24
Y. YONEDAand K. KURIYAMA
GABA is preferentially located in the neurohypophysis (Racagni et al., 1979). Similarly, the adenohypophysi~, has no activity of G A D which catalyzes the formation of GABA despite the occurrence of its degrading enzyme (Racagni et al., 1979), as described in the review of Dr DeFeudis. These results make it reasonable to assume that GABA may modulate the secretion of anterior pituitary hormones through eliciting its non-neurotransmitter action. Similar mysteriousness is seen in other endocrine organs including rat ovary. This organ is reported to have a high affinity uptake system for GABA (Erd6, 1983), GABA receptor binding sites with high affinity (Erd6 and Lapis, 1982), and the activity of G A D (Schaeffer and Hsueh, 1982) as discussed by Dr DeFeudis. In contrast, it has been demonstrated that the presence of high levels of GABA in the rat ovary is attributable to the contamination with the oviduct tissue which contains GABA over 2.5 times the amount present in the whole brain (del Rio, 1981). The existence of higher levels of GABA in the rat oviduct than those in the brain has been confirmed (Erd6, Rosdy and Szporny, 1982). It has been also shown that the endogenous levels of GABA in the oviduct vary during the ovarian cycle (del Rio, 1980). These findings again raise the question; what is the functional significance of GABA in the endocrine organs? Does endogenous GABA modulate the secretion of various hormones through exerting an inhibitory neurotransmitter action or by eliciting a significant action other than a neurotransmitter? If the former is the case, it should be demonstrated that the endocrine organ has GABAergic innervations. Criteria for the identification of a neurotransmitter should be, at least, satisfied in the endocrine tissues. If the latter is the case, it is conceivable that GABA may exhibit a general action on the mechanism of excitation-secretion coupling which in turn results in the alteration of membrane excitability in the excitable tissues such as brain and endocrine organ. It has been demonstrated that the structurally-related compound, taurine, induces an alteration of the release of various neurotransmitters through the interaction with intracellular free Ca -~ available for the release (Kuriyama et al., 1978; Kuriyama, 1980). In contrast, it has been well established that environmental alterations affect the endocrine as well as nervous systems in addition to inducing various neuropsychiatric symptoms. For instance, a stressful manipulation produces various behavioral changes in laboratory animals including the depressive psychosis (Sherman et al., 1979) with a concomitant stimu-
lation of the hypothalamo-pituitary-adrenal axis (Fujiide and Hiroshige, 1978; DeTurck and Vogel, 1982). Application of a stressor also results in a significant alteration in the metabolism and/or the function of other putative neurotransmitters in the central and peripheral nervous systems such as epinephrine, norepinephrine, dopamine and 5-hydroxytryptamine (Thierry et al., 1968; Kvetnansky et al., 1977; McCarty and Kopin, 1978). Recently, it has been shown that a stressful circumstance induces a significant alteration of GABA metabolism in the striatum and hypothalamus without affecting that in other central structures (Yoneda et al., 1983). Considering these findings together with the fact that GABA indeed modulates the secretion of various hormones from the pituitary (for details, see the review by Dr DeFeudis), it seems reasonable to assume that GABA may be involved in the occurrence of various behavioral changes including neuropsychiatric disturbance through the interaction with endocrine systems. CONCLUSION
Accumulating evidence has indicated that GABA is indeed present in various peripheral tissues including endocrine organs in addition to the CNS. Although it is clear that GABA plays an inhibitory neurotransmitter role in the CNS, little has been clarified with regard to the functional significance of this amino acid in the peripheral tissues. Several lines of evidence suggest a possible modulatory action of GABA on the secretion of hormones from various endocrine organs as reviewed by Dr DeFeudis. The exact molecular mechanism underlying these phenomena as well as the origin of this peripheral GABA, however, remain to be elucidated. Since there is no doubt that GABA has a metabolic significance as an intermediate of the Krebs cycle even in the CNS, it seems possible that the peripheral GABA may merely reflect the metabolic activity of the " G A B A shunt" in the tissue. Therefore, one of the urgent problems to be solved in the future studies is the demonstration of the presence of metabolic pathway for the biosynthesis as well as degradation of GABA in the peripheral tissues including endocrine organs. Since it has been postulated that there may exist some compartments of GABA and/or of its metabolic precursor, L-glutamic acid, in the brain, studies on the clarification of compartmentation of GABA are also essential for concluding the functional significance of this amino acid in the secretion of hormones. Elucidation of such problems will automatically give us a clue for the understanding
Critique of the relationship between G A B A , h o r m o n e s a n d neuropsychiatric disorders.
REFERENCES
Awapara J., Landua A. J., Fuerst R. and Scale B. (1950). Free y-aminobutyric acid in brain. J. biol. Chem. 187, 35-39. del Rio R. M. (1981). y-Aminobutyric acid system in rat oviduct. J. biol. Chem. 256, 9816-9819. DeTurck K. H. and Vogel W. H. (1982). Effect of acute ethanol on plasma and brain catecholamine levels in stressed and unstressed rats: Evidence for an ethanolstress interaction. J. Pharmac. exp. Ther. 223, 348-354. Erd6 S. L. and Lapis E. (1982). Bicuculline sensitive GABA receptors in rat ovary. Eur. J. Pharmac. 85, 243-246. Erd6 S. L., Rosdy B. and Szporny L. (1982). Higher GABA concentrations in Fallopian tube than in brain of the rat. J. Neurochem. 38, 1174-1176. Erd6 S. L. (1983). High affinity, sodium-depdendent y-aminobutyric acid uptake by slices of rat ovary. J. Neurochem. 40, 582-584. Fahn S. and Crt6 L. J. (1968). Regional distribution of gamma-aminobutyric acid (GABA) in brain of the rhesus monkey. J. Neurochem. 15, 209-213. Fujiide K. and Hiroshige T. (1978). Changes in rat hypothalamic content of corticotrophin-releasing factor (CRF) activity, plasma ACTH and corticosterone under stress and the effect of cycloheximide. Acta endocr., Copenh. 89, 10-19. Graham L. T. Jr, Shank R. P., Werman R. and Aprison M. H. (1967). Distribution of some synaptic transmitter suspects in cat spinal cord: Glutamic acid, aspartic acid, Gamma-aminobutyric acid, glycine, and glutamine. J. Neurochem. 14, 465~,72. Grofov~ I. and Rinvik E. (1970). An experimental electron microscopic study on the striatonigral projection in the cat. Exp. Brain Res. l l , 249-262. Kanazawa I., Miyata Y., Toyokura Y. and Otsuka M. (1973). The distribution of gamma-aminobutyric acid (GABA) in the human substantia nigra. Brain Res. 51, 363-365. Kimura H. and Kuriyama K. (1975). Distribution of gamma-aminobutyric acid (GABA) in the rat hypothalamus: Functional correlates of GABA with activities of appetite controlling mechanisms. J. Neurochem. 24, 903-907. Kuriyama K., Haber B., Sisken B. and Roberts E. (1966). The ~/-aminobutyric acid system in rabbit cerebellum. Proc. natn. acad. Sci., U.S.A. 55, 846-852. Kuriyama K., Siskin B., Haber B. and Roberts E. (1968). The y-aminobutyric acid system in rabbit retina. Brain Res. 9, 165-168. Kuriyama K. and Yoneda Y. (1978). Morphine-induced alterations of 7-aminobutyric acid and taurine contents and L-glutamate decarboxylase activity in rat spinal cord and thalamus: Possible correlates with analgesic action of morphine. Brain Res. 148, 163-179. Kuriyama K., Muramatsu M., Nakagawa K. and Kakita K. (1978). Modulating role of taurine on release of neurotransmitters and calcium transport in excitable tissues. In: Taurine and Neurological Disorders (Barbeau A. and
25
Huxtable R. J., eds), pp. 201-216. Raven Press, New York. Kuriyama K. (1980). Taurine as a neuromodulator. Fedn Proc. 39, 2680-2684. Kvetnansky R., Sun C. L., Torda T. and Kopin I. J. (1977). Plasma epinephrine and norepinephrine levels in stressed rats. Effect of adrenalectomy. Pharmacologist 19, 241-251. McCarty R. and Kopin I. J. (1978). Sympatho-adrenal medullary activity and behavior during exposure to footshock stress: a comparison of seven rat strains. Physiol. Behav. 21, 567-572. McLaughlin B. J., Wood J. G., Saito K., Barber R., Vaughn J. E., Roberts E. and Wu J.-Y. (1974). The fine structural localization of glutamate decarboxylase in synaptic terminals of rodent cerebellum. Brain Res. 76, 377-391. McLaughlin B. J., Wood J. G., Saito K., Roberts E. and Wu J.-Y. (1975). The fine structural localization of glutamate decarboxylase in developing axonal processes and presynaptic terminals of cerebellum. Brain Res. 85, 355-371. Miyata Y. and Otsuka M. (1972). Distribution of ~-aminobutyric acid in cat spinal cord and the alteration produced by local ischaemia. J. Neurochem. 19, 1833-1834. Okada Y. and Shimada C. (1975). Distribution of 7-aminobutyric acid (GABA) and glutamate decarboxylase activity in the guinea-pig hippocampus-microassay method for the determination of GAD activity. Brain Res. 98, 202-206. Okada Y., Taniguchi H. and Shimada C. (1976), High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. Science 194, 620-622. Racagni G., Apud J. A., Locatelli V., Cocchi D., Nistico G., Di Giorgio R. M. and Mfiller E. E. (1979). GABA of CNS origin in the rat anterior pituitary inhibits prolactin secretion. Nature 281, 575-578. Rivier C. and Vale W. (1977). Effects of 7-aminobutyric acid and histamine on prolactin secretion in the rat. Endocrinology 101, 506-511. Roberts E. and Frankel S. (1950). ~,-Aminobutyric acid in brain: Its formation from glutamic acid. J. biol. Chem. 187, 55-63. Roberts E., Lowe I. P., Guth L. and Jelinek B. (1958). Distribution of gamma-aminobutyric acid and other amino acids in nervous tissue of various species. J. exp. Zool. 138, 313-328. Roberts E., Chase T. N. and Tower D. B. (1976). GABA in Nervous System Function, Raven Press, New York. Schaeffer J. M. and Hsueh A. J. W. (1982). Identification of gamma-aminobutyric acid and its binding sites in the rat ovary. Life Sci. 30, 1599-1604. Shally A. V., Redding T. W., Arimura A., Dupont A. and Linthicum G. L. (1977). Isolation of 7-aminobutyric acid from pig hypothalami and demonstration of its prolactin release-inhibiting (PIF) activity in vivo and in vitro. Endocrinology 100, 681-691. Sherman A. D., Allers G. L., Petty F. and Henn F. A. (1979). A neuropharmacologically-relevant animal model of depression. Neuropharmacology 18, 891-893. Thierry A. M., Javoy F., Glowinski J. and Kety S. S. (1968). Effect of stress on the metabolism of norepinephrine, dopamine and serotonin in the central nervous system of the rat. I. Modification of norepinephrine turnover. J. Pharmac. exp. Ther. 163, 163-172.
26
Y. YONEDA and K. KURIYAMA
Tomiko S. A., Taraskevick P. S. and Douglas W. W. (1983). GABA acts directly on cells of pituitary pars intermedia to alter hormone output. Nature 301, 706-707. Udenfriend S. (1950). Identification of ),-aminobutyric acid in brain by the isotope derivative method. J. biol. Chem. 187, 65-69. Yoneda Y. and Kuriyama K. (1978). A comparison of microdistributions of taurine and cysteine sulphinate decarboxylatse activity with those of GABA and L-
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