Summary
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1.
Segments of the guinea-pig ileum were incubated in Tyrode's solution containing 3 μM propranolol. Dopamine, like noradrenaline and clonidine, inhibited the twitch response to field stimulation. The inhibitory action of dopamine remained unchanged in the presence of the dopamine uptake inhibitor nomifensine (1 μM). Tissue from reserpine-pretreated amimals was insensitive to tyramine but the response to dopamine was not affected. It is, therefore, assumed that the effect of dopamine is due to a direct receptor stimulation and not to the release of noradrenaline.
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2.
The inhibitory action of dopamine was not antagonized by the dopamine receptor antagonists cis-flupenthixol, pimozide or domperidone.
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3.
Metoclopramide, sulpiride and tolazoline were competitive antagonists of the inhibitory effects of dopamine. The pA2-values for metoclopramide against dopamine (5.64) noradrenaline (5.52), and clonidine (5.57) did not differ significantly. Likewise, there was no significant difference between the pA2-values for sulpiride (5.30, 5.29, 5.50) and those for tolazoline (6.52, 6.69, 7.02) determined against dopamine, noradrenaline and clonidine.
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4.
Apomorphine inhibited the twitch response, and this inhibition was not affected by tolazoline, sulpiride or pimozide.
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5.
It is concluded that dopamine inhibits the twitch response in the guinea-pig ileum through stimulation of neuronal α-adrenoceptors. Metoclopramide and sulpiride are weak antagonists at these receptors. The results provide no evidence for the existence of specific inhibitory dopamine receptors in the guinea-pig ileum.
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References
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58
DeCarle DJ, Christensen J (1976) A dopamine receptor in esophageal smooth muscle of the opossum. Gastroenterology 70:216–219
Documenta Geigy (1969) Wissenschaftliche Tabellen, equation (672) (7th edition). Ciba-Geigy Ltd., Basel, p 178
Drew GM (1978) Pharmacological characterization of the presynaptic α-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br J Pharmacol 64:293–300
Dubocovich ML, Langer SZ (1980) Dopamine and alpha adrenoceptor agonists inhibit neurotransmission in the cat spleen through different presynaptic receptors. J Pharmacol Exp Ther 212:144–152
Ennis C, Janssen PA, Schnieden H, Cox B (1979) Characterization of receptors on postganglionic cholinergic neurons in the guinea-pig isolated ileum. J Pharm Pharmacol 31:217–221
Ferri S, Reina R, Santagostino A (1977) Dopamine and the depressant action of morphine on stimulated guinea-pig ileum. Br J Pharmacol 59:25–28
Fuder H, Muscholl E (1978) The effects of dopamine on the overflow of endogenous noradrenaline from the perfused rabbit heart evoked by sympathetic nerve stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 305:109–115
Furchgott RF (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Handbuch Exp Pharmakol, vol 33. Springer, Berlin Heidelberg New York, pp 283–335
Goldberg LI, Volkman PH, Kohli JD (1978) A comparison of the vascular dopamine receptor with other dopamine receptors. Ann Rev Pharmacol Toxicol 18:57–79
Hunt P, Raynaud JP, Leven M, Schacht U (1979) Dopamine uptake inhibitors and releasing agents differentiated by the use of synaptosomes and field-stimulated brain slices in vitro. Biochem Pharmacol 28:2011–2016
Illés P, Knoll J (1978) Opiate and dopamine receptors in the isolated nictitating membrane of the cat. Pol J Pharmacol Pharm 30:293–304
Iversen LL, Rogawski MA, Miller RJ (1976) Comparison of the effects of neuroleptic drugs on pre-and postsynaptic dopaminergic mechanism in the rat striatum. Mol Pharmacol 12:251–262
Jenner P, Marsden CD (1979) The substituted benzamides — a novel class of dopamine antagonists. Life Sci 25:479–486
Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96
Kohli JD, Cripe LD (1979) Sulpiride: A weak antagonist of norepinephrine and 5-hydroxytryptamine. Eur J Pharmacol 56:283–286
Laduron PL, Leysen JE (1979) Domperidone, a specific in vitro dopamine antagonist, devoid of in vivo central dopaminergic activity. Biochem Pharmacol 28:2161–2165
Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362
Muscholl E (1966) Release of catecholamines from the heart. In: Von Euler US, Rosell S, Uvnäs B (eds) Mechanisms of release of biogenic amines. Pergamon Press, Oxford, pp 247–260
Paton WDM, Zar MA (1968) The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J Physiol 194:13–33
Rattan S, Goyal RK (1976) Effect of dopamine on the esophageal smooth muscle in vivo. Gastroenterology 70:377–381
Sachs L (1969) Statistische Auswertungsmethoden. 2. Aufl. Springer, Berlin Heidelberg New York
Schild HO (1947) pA, a new scale for the measurement of drug antagonism. Br J Pharmacol 2:189–206
Spedding M (1980) Effects of metoclopramide and isoprenaline in the rat vas deferens; interactions with α-adrenoceptors. Br J Pharmacol 71:113–120
Spedding M (1981) Antagonism of the inhibitory effects of clonidine and dopamine in the guinea-pig ileum by metoclopramide, sultopride and sulpiride. Br J Pharmacol 73: 279P
Valenzuela JE (1976) Dopamine as a possible neurotransmitter in gastric relaxation. Gastroenterology 71:1019–1022
Van Nueten JM, Ennis C, Helsen L, Laduron PM, Janssen PAJ (1978) Inhibition of dopamine receptors in the stomach: An explanation of the gastrokinetic properties of domperidone. Life Sci 23:453–458
Vizi ES, Ronai A, Harsing LG, Knoll J (1978) Presynaptic modulation by norepinephrine and dopamine of acetylcholine release in the peripheral and central nervous system. In: Jenden DJ (ed) Cholinergic mechanisms and psychopharmacology. Plenum Press, London New York, pp 587–603
Vizi ES, Ronai AZ, Knoll J (1974) The inhibitory effect of dopamine on acetylcholine release. Naunyn-Schmiedeberg's Arch Pharmacol 285:R89
Watling KJ, Dowling JE, Iversen LL (1979) Dopamine receptors in the retina may all be linked to adenylate cyclase. Nature 281:578–560
Wikberg J (1978) Differentiation between pre-and postjunctional α-receptors in guinea pig ileum and rabbit aorta. Acta Physiol Scand 103:225–239
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Görich, R., Weihrauch, T.R. & Kilbinger, H. The inhibition by dopamine of cholinergic transmission in the isolated guinea-pig ileum. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 308–312 (1982). https://doi.org/10.1007/BF00501170
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DOI: https://doi.org/10.1007/BF00501170