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Alpha-adrenoceptor and dopamine receptor antagonists do not block the slow inhibitory postsynaptic potential in sympathetic ganglia
226
Brain Research, 187 (1980) 226-230 © Elsevier/North-Holland Biomedical Press
Alpha-adrenoceptor and dopamine receptor antagonists do not block the slow inhibitory postsynaptic potential in sympathetic ganglia
ALISON E. COLE and PATRICIA SHINNICK -GALLAGHER Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77550 (U.S.A.)
(Accepted December 6tb, 1979) Key words: dopamine antagonists -- slow IPSP -- sympathetic neurons
In sympathetic ganglia, stimulation of preganglionic fibers generates a nicotinic fast excitatory postsynaptic potential (F-EPSP) followed by muscarinic slow potentials. Eccles and Libet 7 proposed that the slow inhibitory postsynaptic potential (S-IPSP)* was mediated by a disynaptic pathway. According to the hypothesis, an interneuron, in response to muscarinic excitation, releases a catecholamine which initiates the S-IPSP. Libet 17 proposed dopamine as the catecholamine neurotransmitter involved in this response. If catecholamines are responsible for the S-IPSP, application of exogenous catecholamines should elicit a response identical to the S-IPSP. Catecholamines do hyperpolarize sympathetic ganglia3,5,6, 21. However, to fulfill the criteria that establish agents as neurotransmitters of the physiological response, investigators must prove that the same antagonists block both the catecholamine-induced hyperpolarization and the S-IPSP. In this paper, we report that the S-IPSP in the rabbit superior cervical ganglion (RSCG) is not specifically blocked by catecholamine antagonists. Superior cervical ganglia were excised from adult male New Zealand white rabbits. Responses were recorded from ganglia by a modified sucrose gap techniquelL A physiological solution of the following composition was used to superfuse the preparation (mM): NaC1, 117; KC1, 4.7; CaCI2, 2.5; MgCI2, 1.2; NaHCO3, 25; NaH2PO4, 1.2; glucose, 11.5. We routinely added hexamethonium (5 × 10-4 M) to the superfusate to block the fast excitatory nicotinic response. Drugs were added to the physiological solution and administered by superfusion. Train stimulation of the preganglionic nerve at 40 Hz for 250 msec elicited a maximal S-IPSP response. We initially studied the effects of dopamine antagonists on the S-]PSP response in RSCG. Ganglia were superfused with increasing concentrations (10-8-10 -3 M) of sulpirixle (n = 7) and haloperidol (n = 3). At concentrations of 10-8-10 -6 M no de* Intracellular terminology for the ganglionic potentials will be used throughout this paper.
227
__•.Smv 4 sec
,]
.2 m y
4sec
Fig. 1. Effect of catecholamine antagonists on the slow inhibitory postsynaptic potential (S-IPSP). Ax: control S-IPSP. A2: S-IPSP after treatment of preparation with sulpiride (10-e M) for 30 rain. BI: control S-IPSP in different preparation. B2: S-IPSP after treatment with phentolamine (10-B M) for 30 min. Ba: after treatment with phentolamine for 3 h. All responses were recorded with the sucrose gap method in the presence of 5 × 10-4 M hexamethonium. pression of the S-IPSP was recorded with these drugs. The ineffectiveness of 10-6 M sulpiride on the S-IPSP is shown in Fig. 1A. At 10-z M, sulpiride slightly depressed the S-IPSP. Haloperidol, at concentrations of 10-5 M, depressed the S-IPSP and the other ganglionic potentials. Thus, the depression was non-selective. In addition, haloperidol at 10 -5 M has been shown to block directly-elicited action potentials in spinal ganglia 12. We recorded similar results when the a-adrenoceptor antagonists phentolamine (n = 7) and yohimbine (n = 5) were applied to the RSCG. No depression of the S-IPSP was observed after superfusing the RSCG for 30 rain with 10-~ M phentolamine; even after 3 h of treatment with phentolamine the S-IPSP was unchanged (Fig. 1B). Similar results were obtained with yohimbine (10 -s- 10-5 M). The a-adrenoceptor antagonists depressed the response only at concentrations of 10-4 M and higher. Again, the depression was not selective for the S-IPSP since all potentials, F-EPSP, S-IPSP and S-EPSP (slow excitatory postsynaptic potential), were affected. Phenoxybenzamine (PBZ), an a-adrenoceptor antagonist, non-selectively depressed all the ganglionic potentials at concentrations of 10-8-10 -6 M. After treatment with PBZ (10 -6 M) for 30 min the F-EPSP, S-IPSP and S-EPSP were depressed (Fig. 2A). Since the block was non-selective, the depression by PBZ may be due to an antimuscarinic action and block of the nicotinic receptor mechanism known to occur with this antagonist 11.
228 A
B
~J 4s e c
.2m v
Fig. 2. Effect of phenoxybenzamine and atropine on the S-IPSP. A1: control S-IPSP. A2: S-IPSP after treatment with PBZ (10 -6 M) for 30 min. BI: same as A1 in different preparation. B2: S-IPSP after treatment with atropine (10 -7 M) for 30 rain. All responses were recorded with the sucrose gap method in the presence of 5 × 10 -4 M hexamethonium.
The fl-adrenoreceptor antagonist, L-propranolol (10 -6 M) had no effect on the S-IPSP response in RSCG. Only the muscarinic antagonist atropine 0 0 -7 M) (n = 4) completely antagonized the S-IPSP (Fig. 2B). The fact that atropine eliminate3 the after-potential, even when some F-EPSP remains, is proof that the spike after-hyperpolarization does not contribute to the S-IPSP. The S-EPSP was also blocked because it is likewise initiated through activation of muscarinic receptors. Therefore, atropine could not discriminate between the S-IPSP and S-EPSP. Atropine has been shown to have a similar action in frog ls,2a, cat 24 and rabbit 7,19. The present results show that the S-IPSP is not selectively blocked by catecholamine antagonists. Nakamura 22 also observed that the dopamine receptor antagonist, haloperidol, did not affect the S-IPSP in RSCG. Similarly, haloperidol was ineffective against the catecholamine-induced hyperpolarizations in the SCG of rat a and rabbit 5. In addition, sulpiride, a potent dopamine receptor antagonist did not affect the catecholaminehyperpolarizations ~ or the S-IPSP in concentrations up to 10-a M. Phentolamine and yohimbine, both a-adrenoceptor antagonists, did not selectively inhibit the S-IPSP response. In contrast to dopamine receptor antagonists, these a-adrenoceptor antagonists were the most effective inhibitors of the catecholamineinduced hyperpolarizations in sympathetic ganglia of rat a and rabbit ~. The disynaptic theory for the generation of the S-IPSP was based on the findings that dibenamine 7 and phenoxybenamine 2° antagonized the S-IPSP response. These agents were considered selective a-adrenoceptor antagonists2°; however, it is known that both these agents can inhibit responses to 5-hydroxytryptamine ( 5 - H T ) la, histamine le and acetylcholine1,2,8,9. In our preparation, phenoxybenzamine (10 -6 M) depressed the F-EPSP, S-IPSP and S-EPSP. On the other hand, phentolamine has one-tenth the affinity for 5-HT receptors as for a-adrenoceptors and has fewer secondary actions than other a-adrenoceptor antagonists s-l°. Even phentolamine, a more specific aadrenoceptor antagonist, did not selectively depress the S-IPSP.
229 In conclusion, d o p a m i n e r e c e p t o r a n d a d r e n o c e p t o r a n t a g o n i s t s d o n o t selectively inhibit the S - I P S P response in R S C G . O n l y the m u s c a r i n i c antagonist, atropine, inhibits the S - I P S P a n d S - E P S P w i t h o u t depressing the F - E P S P . These results lend s u p p o r t to the alternative hypothesis for the generation o f the S - I P S P p r o p o s e d by Voile ~5 a n d W e i g h t 26, t h a t acetylcholine directly h y p e r p o l a r i z e s s y m p a t h e t i c ganglia via m u s c a r i n i c receptors. C a t e c h o l a m i n e receptors m a y be present in the R S C G a n d m a y be responsible for a m e m b r a n e h y p e r p o l a r i z a t i o n a-6,21. However, the physiological response - - the S - I P S P - - does n o t a p p e a r to be affected selectively by catecholamine antagonists. Thus, one criteria for establishing a c a t e c h o l a m i n e as the neurot r a n s m i t t e r involved in the S - I P S P has n o t been satisfied. W e t h a n k Dr. Joel P. G a l l a g h e r a n d W i l l i a m Gritfith, I I I for their reviews o f the m a n u s c r i p t a n d Drs. O d d Steinsland a n d D a r y l C h r i s t for their helpful c o m m e n t s a n d assistance with this project.
1 Benfey, B. G. and Grillo, S. A., Antagonism of acetylcholine by adrenaline antagonists, Brit. J. Pharmacol., 20 (1963) 528. 2 Boyd, H., Burnstock, G., Campbell, G., Lowett, A., O'Shea, J. and Wood, M., The cholinergic blocking action of adrenergic blocking agents in the pharmacological analysis of autonomic innervation, Brit. J. Pharmacol., 20 (1963) 418. 3 Brown, D. A. and Caulfield, M. P., Hyperpolarizing 'a-2'-adrenoceptors in rat sympathetic ganglia, Brit. J. Pharmacol., 65 (1979) 435-445. 4 Christ, D. D. and Nishi, S., Site of adrenaline blockade in the superior cervical ganglion of the rabbit, J. PhysioL (Lond.), 213 (1971) 107-117. 5 Cole, A. E. and Shinnick-Gallagher, P., Characterization of a postganglionic catecholamine receptor in the rabbit superior cervical ganglia, Neurosci. Abstr., 9 (1979) in press. 6 DeGroat, W. C. and Volle, R. L., The actions of the catecholamines on the transmission in the superior cervical ganglion of the cat, J. PharmacoL exp. Ther., 154 (1966) 1-13. 7 Eccles, R. M. and Libet, B., Origin and blockade of the synaptic responses of curarized sympathetic ganglia, J. Physiol. (Lond.), 157 (1961) 484--503. 8 Furchgott, R. F., The pharmacology of vascular smooth muscle, Pharmacol. Rev., 7 (1955) 183-265. 9 Furchgott, R. F., The use of fl-haloalkylamines in the differentiation of receptors and in the determination of dissociation constants of receptor-agonist complexes. In N. J. Harper and A. B. Simmonds (Eds.), Advances in Drug Research, Academic Press, London and New York, 1966, pp. 21-55. I0 Furchgott, R. F., The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In O. Eichler, A. Farah, H. Herken and A. D. Welch (Eds.), Handbook of Experimental Pharmacology, Springer-Verlag, Berlin, 1972, pp. 283-335. 11 Furchgott, R. F., Steinsland, O. S. and Wakade, T. D., Studies in prejunctionai muscarinic and nicotinic receptors. In O. Almgren, A. Carlsson and J. Engel (Eds.), Chemical Tools in Catecholamine Research, VoL 2, North-Holland, 1975, pp. 167-174. 12 Gallagher, J. P., Inokuchi, H. and Shinnick-Gallagher, P., Characterization of a mammalian dopamine receptor, Fed. Proc., 38 (1979) 6189. 13 Gyermek, L., Drugs which antagonize 5-hydroxytryptamine and related indolealkylamines. In V. Erspamer (Ed.), 5-Hydroxytryptamine and Related Indolealkylamines, Handbook of Experimental Pharmacology, VoL 19, Springer-Verlag, Berlin, 1966, pp. 471-528. 14 Jenner, P., Elliott, P. N. C., Clow, A., Reavill, C. and Marsden, C. D., A comparison of in vitro and in vivo dopamine receptor antagonism produced by substituted benzamide drug, J. Pharm. PharmacoL, 30 (1978) 4648. 15 Koketsu, K. and Nishi, S., Cholinergic receptors at sympathetic preganglionic nerve terminals, J. PhysioL (Lond.), 196 (1968) 293-310.
230 16 Leonard, F. and Huttrer, C. P., Histamine Antagonists, Natl. Res. Council Natl. Acad. Sci. (U.S.), Chem. Biol. Coord. Center, Rev. 3, 1950. 17 Libet, B., Generation of slow inhibitory and excitatory postsynaptic potentials, Fed. Proc., 29 (1970) 1945. 18 Libet, B., Chichibu, S. and Tosaka, T., Slow synaptic responses and excitability in sympathetic g~mglia of the bullfrog, J. NeurophysioL, 31 (1968) 383-395. 19 Libet, B. and Tosaka, T., Slow inhibitory and excitatory postsynaptic responses in single cells of mammalian sympathetic ganglia, J. Neurophysiol., 32 (1969) 43-50. 20 Libet, B. and Tosaka, T., Dopamine as a synaptic transmitter and modulator in sympathetic ganglia: a different mode of synaptic action, Proc. nat. Acad. Sci. (Wash.), 67 (1970) 667-673. 21 Lundberg, A., Adrenaline and transmission in the sympathetic ganglion of the cat, Acta physiol. scand., 26 (1952) 252-263. 22 Nakamura, J., The effect of neuroleptics in the dopaminergic and cholinergic systems in sympathetic ganglia, Kurume med. J., 25 (1978) 241-253. 23 Nishi, S. and Koketsu, K., Analysis of slow inhibitory postsynaptic potentials of bullfrog sympathetic ganglion, J. Neurophysiol., 31 (1968) 717-728. 24 Skok, V., On the physiological role of slow inhibitory postsynaptic potential in the neurons of sympathetic ganglia. I~n J. P. Ruben, D. P. Purpura, M. V. L. Bennett and E. R. Kandel (Eds.), Electrobiology of Nerve, Synapse and Muscle, Raven Press, New York, 1976, pp. 123-128. 25 Voile, R. L., Ganglionic transmission, Ann. Rev. Pharmacol., 9 (1969) 135-146. 26 Weight, F. F. and Padjen, A., Acetylcholine and slow synaptic inhibition in frog sympathetic ganglion cells, Brain Research, 55 (1973) 225-228.
Brain Research, 187 (1980) 226-230 © Elsevier/North-Holland Biomedical Press
Alpha-adrenoceptor and dopamine receptor antagonists do not block the slow inhibitory postsynaptic potential in sympathetic ganglia
ALISON E. COLE and PATRICIA SHINNICK -GALLAGHER Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77550 (U.S.A.)
(Accepted December 6tb, 1979) Key words: dopamine antagonists -- slow IPSP -- sympathetic neurons
In sympathetic ganglia, stimulation of preganglionic fibers generates a nicotinic fast excitatory postsynaptic potential (F-EPSP) followed by muscarinic slow potentials. Eccles and Libet 7 proposed that the slow inhibitory postsynaptic potential (S-IPSP)* was mediated by a disynaptic pathway. According to the hypothesis, an interneuron, in response to muscarinic excitation, releases a catecholamine which initiates the S-IPSP. Libet 17 proposed dopamine as the catecholamine neurotransmitter involved in this response. If catecholamines are responsible for the S-IPSP, application of exogenous catecholamines should elicit a response identical to the S-IPSP. Catecholamines do hyperpolarize sympathetic ganglia3,5,6, 21. However, to fulfill the criteria that establish agents as neurotransmitters of the physiological response, investigators must prove that the same antagonists block both the catecholamine-induced hyperpolarization and the S-IPSP. In this paper, we report that the S-IPSP in the rabbit superior cervical ganglion (RSCG) is not specifically blocked by catecholamine antagonists. Superior cervical ganglia were excised from adult male New Zealand white rabbits. Responses were recorded from ganglia by a modified sucrose gap techniquelL A physiological solution of the following composition was used to superfuse the preparation (mM): NaC1, 117; KC1, 4.7; CaCI2, 2.5; MgCI2, 1.2; NaHCO3, 25; NaH2PO4, 1.2; glucose, 11.5. We routinely added hexamethonium (5 × 10-4 M) to the superfusate to block the fast excitatory nicotinic response. Drugs were added to the physiological solution and administered by superfusion. Train stimulation of the preganglionic nerve at 40 Hz for 250 msec elicited a maximal S-IPSP response. We initially studied the effects of dopamine antagonists on the S-]PSP response in RSCG. Ganglia were superfused with increasing concentrations (10-8-10 -3 M) of sulpirixle (n = 7) and haloperidol (n = 3). At concentrations of 10-8-10 -6 M no de* Intracellular terminology for the ganglionic potentials will be used throughout this paper.
227
__•.Smv 4 sec
,]
.2 m y
4sec
Fig. 1. Effect of catecholamine antagonists on the slow inhibitory postsynaptic potential (S-IPSP). Ax: control S-IPSP. A2: S-IPSP after treatment of preparation with sulpiride (10-e M) for 30 rain. BI: control S-IPSP in different preparation. B2: S-IPSP after treatment with phentolamine (10-B M) for 30 min. Ba: after treatment with phentolamine for 3 h. All responses were recorded with the sucrose gap method in the presence of 5 × 10-4 M hexamethonium. pression of the S-IPSP was recorded with these drugs. The ineffectiveness of 10-6 M sulpiride on the S-IPSP is shown in Fig. 1A. At 10-z M, sulpiride slightly depressed the S-IPSP. Haloperidol, at concentrations of 10-5 M, depressed the S-IPSP and the other ganglionic potentials. Thus, the depression was non-selective. In addition, haloperidol at 10 -5 M has been shown to block directly-elicited action potentials in spinal ganglia 12. We recorded similar results when the a-adrenoceptor antagonists phentolamine (n = 7) and yohimbine (n = 5) were applied to the RSCG. No depression of the S-IPSP was observed after superfusing the RSCG for 30 rain with 10-~ M phentolamine; even after 3 h of treatment with phentolamine the S-IPSP was unchanged (Fig. 1B). Similar results were obtained with yohimbine (10 -s- 10-5 M). The a-adrenoceptor antagonists depressed the response only at concentrations of 10-4 M and higher. Again, the depression was not selective for the S-IPSP since all potentials, F-EPSP, S-IPSP and S-EPSP (slow excitatory postsynaptic potential), were affected. Phenoxybenzamine (PBZ), an a-adrenoceptor antagonist, non-selectively depressed all the ganglionic potentials at concentrations of 10-8-10 -6 M. After treatment with PBZ (10 -6 M) for 30 min the F-EPSP, S-IPSP and S-EPSP were depressed (Fig. 2A). Since the block was non-selective, the depression by PBZ may be due to an antimuscarinic action and block of the nicotinic receptor mechanism known to occur with this antagonist 11.
228 A
B
~J 4s e c
.2m v
Fig. 2. Effect of phenoxybenzamine and atropine on the S-IPSP. A1: control S-IPSP. A2: S-IPSP after treatment with PBZ (10 -6 M) for 30 min. BI: same as A1 in different preparation. B2: S-IPSP after treatment with atropine (10 -7 M) for 30 rain. All responses were recorded with the sucrose gap method in the presence of 5 × 10 -4 M hexamethonium.
The fl-adrenoreceptor antagonist, L-propranolol (10 -6 M) had no effect on the S-IPSP response in RSCG. Only the muscarinic antagonist atropine 0 0 -7 M) (n = 4) completely antagonized the S-IPSP (Fig. 2B). The fact that atropine eliminate3 the after-potential, even when some F-EPSP remains, is proof that the spike after-hyperpolarization does not contribute to the S-IPSP. The S-EPSP was also blocked because it is likewise initiated through activation of muscarinic receptors. Therefore, atropine could not discriminate between the S-IPSP and S-EPSP. Atropine has been shown to have a similar action in frog ls,2a, cat 24 and rabbit 7,19. The present results show that the S-IPSP is not selectively blocked by catecholamine antagonists. Nakamura 22 also observed that the dopamine receptor antagonist, haloperidol, did not affect the S-IPSP in RSCG. Similarly, haloperidol was ineffective against the catecholamine-induced hyperpolarizations in the SCG of rat a and rabbit 5. In addition, sulpiride, a potent dopamine receptor antagonist did not affect the catecholaminehyperpolarizations ~ or the S-IPSP in concentrations up to 10-a M. Phentolamine and yohimbine, both a-adrenoceptor antagonists, did not selectively inhibit the S-IPSP response. In contrast to dopamine receptor antagonists, these a-adrenoceptor antagonists were the most effective inhibitors of the catecholamineinduced hyperpolarizations in sympathetic ganglia of rat a and rabbit ~. The disynaptic theory for the generation of the S-IPSP was based on the findings that dibenamine 7 and phenoxybenamine 2° antagonized the S-IPSP response. These agents were considered selective a-adrenoceptor antagonists2°; however, it is known that both these agents can inhibit responses to 5-hydroxytryptamine ( 5 - H T ) la, histamine le and acetylcholine1,2,8,9. In our preparation, phenoxybenzamine (10 -6 M) depressed the F-EPSP, S-IPSP and S-EPSP. On the other hand, phentolamine has one-tenth the affinity for 5-HT receptors as for a-adrenoceptors and has fewer secondary actions than other a-adrenoceptor antagonists s-l°. Even phentolamine, a more specific aadrenoceptor antagonist, did not selectively depress the S-IPSP.
229 In conclusion, d o p a m i n e r e c e p t o r a n d a d r e n o c e p t o r a n t a g o n i s t s d o n o t selectively inhibit the S - I P S P response in R S C G . O n l y the m u s c a r i n i c antagonist, atropine, inhibits the S - I P S P a n d S - E P S P w i t h o u t depressing the F - E P S P . These results lend s u p p o r t to the alternative hypothesis for the generation o f the S - I P S P p r o p o s e d by Voile ~5 a n d W e i g h t 26, t h a t acetylcholine directly h y p e r p o l a r i z e s s y m p a t h e t i c ganglia via m u s c a r i n i c receptors. C a t e c h o l a m i n e receptors m a y be present in the R S C G a n d m a y be responsible for a m e m b r a n e h y p e r p o l a r i z a t i o n a-6,21. However, the physiological response - - the S - I P S P - - does n o t a p p e a r to be affected selectively by catecholamine antagonists. Thus, one criteria for establishing a c a t e c h o l a m i n e as the neurot r a n s m i t t e r involved in the S - I P S P has n o t been satisfied. W e t h a n k Dr. Joel P. G a l l a g h e r a n d W i l l i a m Gritfith, I I I for their reviews o f the m a n u s c r i p t a n d Drs. O d d Steinsland a n d D a r y l C h r i s t for their helpful c o m m e n t s a n d assistance with this project.
1 Benfey, B. G. and Grillo, S. A., Antagonism of acetylcholine by adrenaline antagonists, Brit. J. Pharmacol., 20 (1963) 528. 2 Boyd, H., Burnstock, G., Campbell, G., Lowett, A., O'Shea, J. and Wood, M., The cholinergic blocking action of adrenergic blocking agents in the pharmacological analysis of autonomic innervation, Brit. J. Pharmacol., 20 (1963) 418. 3 Brown, D. A. and Caulfield, M. P., Hyperpolarizing 'a-2'-adrenoceptors in rat sympathetic ganglia, Brit. J. Pharmacol., 65 (1979) 435-445. 4 Christ, D. D. and Nishi, S., Site of adrenaline blockade in the superior cervical ganglion of the rabbit, J. PhysioL (Lond.), 213 (1971) 107-117. 5 Cole, A. E. and Shinnick-Gallagher, P., Characterization of a postganglionic catecholamine receptor in the rabbit superior cervical ganglia, Neurosci. Abstr., 9 (1979) in press. 6 DeGroat, W. C. and Volle, R. L., The actions of the catecholamines on the transmission in the superior cervical ganglion of the cat, J. PharmacoL exp. Ther., 154 (1966) 1-13. 7 Eccles, R. M. and Libet, B., Origin and blockade of the synaptic responses of curarized sympathetic ganglia, J. Physiol. (Lond.), 157 (1961) 484--503. 8 Furchgott, R. F., The pharmacology of vascular smooth muscle, Pharmacol. Rev., 7 (1955) 183-265. 9 Furchgott, R. F., The use of fl-haloalkylamines in the differentiation of receptors and in the determination of dissociation constants of receptor-agonist complexes. In N. J. Harper and A. B. Simmonds (Eds.), Advances in Drug Research, Academic Press, London and New York, 1966, pp. 21-55. I0 Furchgott, R. F., The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In O. Eichler, A. Farah, H. Herken and A. D. Welch (Eds.), Handbook of Experimental Pharmacology, Springer-Verlag, Berlin, 1972, pp. 283-335. 11 Furchgott, R. F., Steinsland, O. S. and Wakade, T. D., Studies in prejunctionai muscarinic and nicotinic receptors. In O. Almgren, A. Carlsson and J. Engel (Eds.), Chemical Tools in Catecholamine Research, VoL 2, North-Holland, 1975, pp. 167-174. 12 Gallagher, J. P., Inokuchi, H. and Shinnick-Gallagher, P., Characterization of a mammalian dopamine receptor, Fed. Proc., 38 (1979) 6189. 13 Gyermek, L., Drugs which antagonize 5-hydroxytryptamine and related indolealkylamines. In V. Erspamer (Ed.), 5-Hydroxytryptamine and Related Indolealkylamines, Handbook of Experimental Pharmacology, VoL 19, Springer-Verlag, Berlin, 1966, pp. 471-528. 14 Jenner, P., Elliott, P. N. C., Clow, A., Reavill, C. and Marsden, C. D., A comparison of in vitro and in vivo dopamine receptor antagonism produced by substituted benzamide drug, J. Pharm. PharmacoL, 30 (1978) 4648. 15 Koketsu, K. and Nishi, S., Cholinergic receptors at sympathetic preganglionic nerve terminals, J. PhysioL (Lond.), 196 (1968) 293-310.
230 16 Leonard, F. and Huttrer, C. P., Histamine Antagonists, Natl. Res. Council Natl. Acad. Sci. (U.S.), Chem. Biol. Coord. Center, Rev. 3, 1950. 17 Libet, B., Generation of slow inhibitory and excitatory postsynaptic potentials, Fed. Proc., 29 (1970) 1945. 18 Libet, B., Chichibu, S. and Tosaka, T., Slow synaptic responses and excitability in sympathetic g~mglia of the bullfrog, J. NeurophysioL, 31 (1968) 383-395. 19 Libet, B. and Tosaka, T., Slow inhibitory and excitatory postsynaptic responses in single cells of mammalian sympathetic ganglia, J. Neurophysiol., 32 (1969) 43-50. 20 Libet, B. and Tosaka, T., Dopamine as a synaptic transmitter and modulator in sympathetic ganglia: a different mode of synaptic action, Proc. nat. Acad. Sci. (Wash.), 67 (1970) 667-673. 21 Lundberg, A., Adrenaline and transmission in the sympathetic ganglion of the cat, Acta physiol. scand., 26 (1952) 252-263. 22 Nakamura, J., The effect of neuroleptics in the dopaminergic and cholinergic systems in sympathetic ganglia, Kurume med. J., 25 (1978) 241-253. 23 Nishi, S. and Koketsu, K., Analysis of slow inhibitory postsynaptic potentials of bullfrog sympathetic ganglion, J. Neurophysiol., 31 (1968) 717-728. 24 Skok, V., On the physiological role of slow inhibitory postsynaptic potential in the neurons of sympathetic ganglia. I~n J. P. Ruben, D. P. Purpura, M. V. L. Bennett and E. R. Kandel (Eds.), Electrobiology of Nerve, Synapse and Muscle, Raven Press, New York, 1976, pp. 123-128. 25 Voile, R. L., Ganglionic transmission, Ann. Rev. Pharmacol., 9 (1969) 135-146. 26 Weight, F. F. and Padjen, A., Acetylcholine and slow synaptic inhibition in frog sympathetic ganglion cells, Brain Research, 55 (1973) 225-228.