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Effects of galanin on rat locus coeruleus neurones; Interaction with noradrenaline and [MET5]enkephalin
NEUROPEPTIDES
IN NORMAL
AND PATHOLOGICAL
FUNCTION
from the control values of 8.7 f 1.4 to 2.4 + 0.6 (p < 0.01). These results suggest that substance P released from sensory nerves in the airway is an endogenous substance causing the cough and the substance P antagonist can be the drug for treatment of a cough in respiratory diseases.
Effects of Thyrotropin-Releasing Hormone (TRH) on the Cardiovascular System in Cats and Monkeys E. E. Seligsohn Dept of Physiology & Med Biophysics, Uppsala University, Box 572, S-75 1 23 Uppsala, Sweden The neuropeptide TRH is widely distributed in the CNS. In addition to the release of TSH and prolactin from the pituitary gland TRH is known to elicit a variety of physiological effects including sympathetic activation and cerebral vasodilation in rabbits under different types of anaesthesia (1, 2). TRH has been reported to exert beneficial effects during cerebral ischemia and spinal shock. A cerebrovasodilating effect of TRH has been reported in rats (2) and cats (3). The present study was carried out to further investigate the effects of TRH in different species Eight cats under a-chloralose anaesthesia were given 0.2 mg kg’ and 2 mg kg’ TRH i.v. and 6 monkeys under anaesthesia with urethane were given 0.1 mg kg’ and 1.O mg kg-’ TRH. The blood flow was measured, in control situation and 5 min after each TRH injection, using the tracer micropshere method. In the cat TRH elicited significant increases in mean arterial blood pressure (MAP), heart rate (HR) and cardiac index (CI). However, only minor effects on the peripheral blood flows were seen and there were no effects of TRH on the cerebral blood flow (CBF). In the monkey after administration of 1.O mg kg-’ TRH, a small increase in MAP was seen. HR and CI were not affected. In the spleen TRH elicited vasoconstriction (p < 0.05). The administration of 1.Omg kg-’ caused an increase in CBFtot by 56 + 11% (p < 0.01). Our results indicate that the effect of TRH on the cardiovascular system varies between species. In the cat the main effects are seen in the heart. These effects may be due to an activation of the sympathetic nerves to the heart or to the adrenal glands. In the monkey the heart is unaffected and the cerebral vasodilating effect dominates. Hugoson-Seligsohn, E. E. & Koskinen L.-O. D. (1989). Br. J. Pharmacol. 97: 190-196. 2. Koskinen, L.-O. D. (1989). Ann. New. York. Acad. Sci. 553: 1.
353-369. 3. Mirzoyan, 316.
R. S. et al. (1985). Bull. Exper. Biol. Med. 99: 3 14-
61
Effects of Galanin on Rat Locus Coeruleus Neurones; Interaction with Noradrenaline and [METs]Enkephalin J. Sevcik, E. P. Finta, W. Niirenberg and P. Illes Department of Pharmacology, Uriversity of Freiburg, Hermann-Herder-Strasse 5, D-7800 Freiburg, Germany Histological findings indicate the presence of galanin and enkephalin immunoreactivities in central noradrenergic neurones of the nucleus locus coeruleus (LC) (1). Moreover, it has been demonstrated that, in the LC, both a?-adrenoceptor and opioid agonists increase the same potassium conductance and, thereby, produce hyperpolarization and a depression of the spontaneous discharge of action potentials (2). In pontine slices of the rat brain. galanin also decreased the firing rate of LC neurones (see also Ref. 3) by hyperpolarizing the cells. When the membrane potential was increased by a constant hyperpolarizing current in order to inhibit the generation of spontaneous action potentials, galanin reduced the apparent input resistance. In further experiments, noradrenaline, [Met5]enkephalin and galanin concentrationdependently depressed the firing rate. Since the al-adrenoceptor antagonist rauwolscine, but not the a,-adrenoceptor antagonist prazosin counteracted the effect of noradrenaline, it may be assumed that noradrenaline activates only a,-receptors. Similarly, the strong antagonism between the preferential opioid p-antagonist naloxone and [Mets]enkephalin, in conjunction with the weak antagonism between the preferential opioid b-antagonist ICI 174864 and [Met5]enkephalin (4) suggest the sole existence of F-receptors. Neither rauwolscine nor naloxone altered the fuing on their own Rauwolscine potentiated the effect of [Mets]enkephalin, but not the action of galanin. By contrast, naloxone did not interfere either with noradrenaline or with galanin. The effect of [Mets] enkephalin was unchanged by preincubation with noradrenaline. Furthermore, [Met’lenkephalin or noradrenaline produced the same inhibition, both in the presence and absence of galanin. In conclusion, galanin appears to depress the firing rate of LC neurones by increasing a potassium conductance, in a similar manner as noradrenaline and [Met5]enkephalin do. Moreover. among a,-adrenoceptors, opioid p-receptors and galaninreceptors only the first two types appear to interact with each other. The site of this interaction is probably in the neuronal membrane and not in the common signal transduction system. Marshall. C. K. and Finlayson, P. G. (1988). In: Avoli, M., Reader, T. A., Dykes, R. W. and Gloor, P. (eds) Neurotransmitters and Cortical Function. Plenum Publishing Corporation, New York, p. 373-390. North. R. A. and Williams. J. T. C1985). J. Phvsiol. 364: 265 i 280. Seutin, V., Verbanck, P., Massotte, L. and Dresse. A. (1989). Eur. J. Pharmacol. 164: 373-376. Williams, J. T. and North. R. A. (1984). Molec. Pharmacol. 26: 489-497.
IN NORMAL
AND PATHOLOGICAL
FUNCTION
from the control values of 8.7 f 1.4 to 2.4 + 0.6 (p < 0.01). These results suggest that substance P released from sensory nerves in the airway is an endogenous substance causing the cough and the substance P antagonist can be the drug for treatment of a cough in respiratory diseases.
Effects of Thyrotropin-Releasing Hormone (TRH) on the Cardiovascular System in Cats and Monkeys E. E. Seligsohn Dept of Physiology & Med Biophysics, Uppsala University, Box 572, S-75 1 23 Uppsala, Sweden The neuropeptide TRH is widely distributed in the CNS. In addition to the release of TSH and prolactin from the pituitary gland TRH is known to elicit a variety of physiological effects including sympathetic activation and cerebral vasodilation in rabbits under different types of anaesthesia (1, 2). TRH has been reported to exert beneficial effects during cerebral ischemia and spinal shock. A cerebrovasodilating effect of TRH has been reported in rats (2) and cats (3). The present study was carried out to further investigate the effects of TRH in different species Eight cats under a-chloralose anaesthesia were given 0.2 mg kg’ and 2 mg kg’ TRH i.v. and 6 monkeys under anaesthesia with urethane were given 0.1 mg kg’ and 1.O mg kg-’ TRH. The blood flow was measured, in control situation and 5 min after each TRH injection, using the tracer micropshere method. In the cat TRH elicited significant increases in mean arterial blood pressure (MAP), heart rate (HR) and cardiac index (CI). However, only minor effects on the peripheral blood flows were seen and there were no effects of TRH on the cerebral blood flow (CBF). In the monkey after administration of 1.O mg kg-’ TRH, a small increase in MAP was seen. HR and CI were not affected. In the spleen TRH elicited vasoconstriction (p < 0.05). The administration of 1.Omg kg-’ caused an increase in CBFtot by 56 + 11% (p < 0.01). Our results indicate that the effect of TRH on the cardiovascular system varies between species. In the cat the main effects are seen in the heart. These effects may be due to an activation of the sympathetic nerves to the heart or to the adrenal glands. In the monkey the heart is unaffected and the cerebral vasodilating effect dominates. Hugoson-Seligsohn, E. E. & Koskinen L.-O. D. (1989). Br. J. Pharmacol. 97: 190-196. 2. Koskinen, L.-O. D. (1989). Ann. New. York. Acad. Sci. 553: 1.
353-369. 3. Mirzoyan, 316.
R. S. et al. (1985). Bull. Exper. Biol. Med. 99: 3 14-
61
Effects of Galanin on Rat Locus Coeruleus Neurones; Interaction with Noradrenaline and [METs]Enkephalin J. Sevcik, E. P. Finta, W. Niirenberg and P. Illes Department of Pharmacology, Uriversity of Freiburg, Hermann-Herder-Strasse 5, D-7800 Freiburg, Germany Histological findings indicate the presence of galanin and enkephalin immunoreactivities in central noradrenergic neurones of the nucleus locus coeruleus (LC) (1). Moreover, it has been demonstrated that, in the LC, both a?-adrenoceptor and opioid agonists increase the same potassium conductance and, thereby, produce hyperpolarization and a depression of the spontaneous discharge of action potentials (2). In pontine slices of the rat brain. galanin also decreased the firing rate of LC neurones (see also Ref. 3) by hyperpolarizing the cells. When the membrane potential was increased by a constant hyperpolarizing current in order to inhibit the generation of spontaneous action potentials, galanin reduced the apparent input resistance. In further experiments, noradrenaline, [Met5]enkephalin and galanin concentrationdependently depressed the firing rate. Since the al-adrenoceptor antagonist rauwolscine, but not the a,-adrenoceptor antagonist prazosin counteracted the effect of noradrenaline, it may be assumed that noradrenaline activates only a,-receptors. Similarly, the strong antagonism between the preferential opioid p-antagonist naloxone and [Mets]enkephalin, in conjunction with the weak antagonism between the preferential opioid b-antagonist ICI 174864 and [Met5]enkephalin (4) suggest the sole existence of F-receptors. Neither rauwolscine nor naloxone altered the fuing on their own Rauwolscine potentiated the effect of [Mets]enkephalin, but not the action of galanin. By contrast, naloxone did not interfere either with noradrenaline or with galanin. The effect of [Mets] enkephalin was unchanged by preincubation with noradrenaline. Furthermore, [Met’lenkephalin or noradrenaline produced the same inhibition, both in the presence and absence of galanin. In conclusion, galanin appears to depress the firing rate of LC neurones by increasing a potassium conductance, in a similar manner as noradrenaline and [Met5]enkephalin do. Moreover. among a,-adrenoceptors, opioid p-receptors and galaninreceptors only the first two types appear to interact with each other. The site of this interaction is probably in the neuronal membrane and not in the common signal transduction system. Marshall. C. K. and Finlayson, P. G. (1988). In: Avoli, M., Reader, T. A., Dykes, R. W. and Gloor, P. (eds) Neurotransmitters and Cortical Function. Plenum Publishing Corporation, New York, p. 373-390. North. R. A. and Williams. J. T. C1985). J. Phvsiol. 364: 265 i 280. Seutin, V., Verbanck, P., Massotte, L. and Dresse. A. (1989). Eur. J. Pharmacol. 164: 373-376. Williams, J. T. and North. R. A. (1984). Molec. Pharmacol. 26: 489-497.