Characterization of receptors on postganglionic cholinergic neurons in the guinea-pig isolated ileum

Abstract

Dopamine, apomorphine, noradrenaline and isoprenaline reduced the response of the isolated guinea-pig ileum to exogenous acetylcholine by a maximum of 40 %. Propranolol reversed this inhibition whilst phentolamine and pimozide were ineffective, suggesting that the drugs were acting on a post-synaptic 8-adrenoceptor. The same agonists were more effective as inhibitors of the response to transmural electrical stimulation of the ileum, lower doses producing almost complete inhibition. This inhibition was partially antagonized by phentolamine, pimozide and propranolol. Clonidine proved to be the most potent inhibitor of the response to transmural electrical stimulation, whilst phenylephrine was ineffective. PA, determinations showed that phentolamine was a potent antagonist of clonidine but a weak antagonist of apomorphine whilst for pimozide the opposite was true. The results suggest that there are two populations of prejunctional receptors on the cholinergic nerves innervating the smooth muscle of the guinea-pig ileum. One receptor is similar to a classical prejunctional a-adrenoceptor and the other resembles a central dopamine receptor.

Dopamine Agonists/Antagonists in the Treatment of Gastrointestinal Diseases

“…Dopamine inhibited the responses to exogenous acetylcholine and to electrical field stimulation (Ennis et al, 1979;Gorich et aI., 1982). Whether or not the effects of dopamine and apomorphine, which also inhibits the response to electrical field stimulation, represent an interaction with specific dopamine receptors is controversial, as is presented in Section 4 of this chapter.…”

“…Thus, it appears that in the guinea pig ileum the dopamine responses are mediated by adrenoceptors. This is controversial, as others have suggested that the guinea pig ileum contains two populations of prejunctional receptors on cholinergic neurons, one of which is an adrenoceptor and the other a dopamine receptor (Ennis et al, 1979). Evidence for adrenergically mediated dopamine responses is also available from isolated opossum duodenal longitudinal smooth muscle, where the responses were abolished by either phenoxybenzamine or phentolamine in each preparation tested (Anuras, 1981).…”

Evidence of ascending release of acetylcholine from the locally distended guinea pig ileum.

“…It is conceivable that ascending release of ACh during the local distension may be modulated presynaptically through a-adrenergic re ceptors (8)(9)(10)(11). The investigation of this possibility, however, need further experi ments.…”

Inhibitory Effect of Octopamine on the Release of Endogenous Acetylcholine From Isolated Myenteric Synaptosomes of Guinea‐pig

“…Dopaminergic receptor had recently been subclassified into DA-1 and DA-2 types (Hilditch & Drew 1985). In the guinea-pig ileum, inhibition of cholinergic twitch responses to field stimulation by dopamine was introduced as an action of DA receptors (Ennis et al 1979). Detailed pharmacological analysis of this effect led to the conclusion that it is mediated through a-adrenoceptors on cholinergic neurons (Gorich et al 1982;Zar et al 1982).…”