Regulation of gastrin and somatostatin secretion by intramural neurons: effect of nicotinic receptor stimulation with dimethyl-phenylpiperazinium.
The nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium was used to examine the intramural neural regulation and the functional linkage of gastrin and somatostatin the isolated vascularly perfused rat stomach. 1,1-Dimethyl-4-phenylpiperazinium (10(-5) to 10(-4) M) caused a biphasic dose-dependent increase in gastrin secretion. The gastrin response was abolished by hexamethonium but only partly inhibited (35% at the higher dose of 1,1-dimethyl-4-phenylpiperazinium) by atropine. The same dose of atropine inhibited the maximal gastrin response to the muscarinic agonist, methacholine, by 80%. From this it was concluded that 1,1-dimethyl-4-phenylpiperazinium activates intramural cholinergic and noncholinergic neurons to cause gastrin secretion, 1,1-dimethyl-4-phenylpiperazinium also caused a biphasic, dose-dependent increase in somatostatin secretion. The somatostatin response was completely inhibited by atropine and hexamethonium. Since muscarinic cholinergic agonists cause inhibition of somatostatin secretion, the observed net increase in somatostatin suggests that 1,1 dimethyl-4-phenylpiperazinium activated predominantly a noncholinergic stimulatory neuron. It is hypothesized that this neuron is identical to the gastrin-stimulating noncholinergic neurons and that it releases bombesin, a stimulant of gastrin and somatostatin secretion known to be present in gastric mucosal nerve terminals. The results of this study are consistent with a previously proposed model according to which gastrin secretion is regulated by the activity of two interdependent intramural neurons: a cholinergic neuron that causes gastrin secretion via inhibition of somatostatin and a noncholinergic neuron that releases a synergistic, direct stimulant of gastrin secretion, most likely bombesin.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001839:Bombesin / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013004:Somatostatin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013268:Stimulation, Chemical
D005755:Gastrins; D006584:Hexamethonium Compounds; D008688:Methacholine Compounds; D010879:Piperazines; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D013004:Somatostatin; D004246:Dimethylphenylpiperazinium Iodide; D001285:Atropine; D001839:Bombesin