Pharmacological studies on the mechanisms underlying the inhibitory and excitatory effects of clonidine on gastric acid secretion.
The effects of clonidine on gastric acid secretion were investigated using various pharmacological preparations both in vivo and in vitro. In conscious pylorus-ligated rats clonidine produced a marked reduction of gastric secretion which was prevented by yohimbine, while in anesthetized pylorus-ligated rats the drug failed to affect gastric secretion. In stomach lumen-perfused rats, insulin-stimulated secretion was inhibited by clonidine; in contrast, the drug markedly potentiated bethanechol-evoked gastric secretion; this increase was fully prevented by cimetidine. In isolated preparations of guinea-pig gastric fundus, both spontaneous and bethanechol-induced hypersecretion were significantly enhanced by clonidine; this enhancement was also inhibited by cimetidine. The release of acetylcholine, measured at rest and during vagus nerve stimulation of both guinea-pig and rat isolated stomachs, was significantly inhibited by clonidine: this effect was prevented by yohimbine. Overall results indicate that clonidine possesses both inhibitory and excitatory effects on gastric acid secretion. The inhibitory effect appears to be mediated through the activation of presynaptic alpha 2-receptors which modulate acetylcholine release from the vagus nerve, while the excitatory action seems to depend on histamine-like properties of the drug.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects
D006632:Histamine; D003000:Clonidine; D000109:Acetylcholine