Pharmacological characterization of 5-hydroxytryptamine-induced motor activity (in vitro) in the guinea pig gastric antrum and corpus

Add time:09/10/2019    Source:sciencedirect.com

In order to characterize the receptor subtypes involved in 5-hydroxytryptamine (5-HT)-induced circular muscle motor responses of the guinea pig gastric antrum and corpus, we examined the effects of several antagonists in vitro. 5-HT evoked concentration-dependent contractions of the gastric antrum and relaxations of the corpus. 5-HT-induced antral contractions were abolished by pretreatment with atropine and tetrodotoxin. Methysergide, ketanserin, granisetron and [1-[2-(methylsulphonylamino)ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate maleate salt (GR113808A), but neither 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190) nor N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-l-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-l-alaninamide (F inhibited 5-HT (3 × 10−6 M: submaximal concentration)-induced antral contractions concentration dependently and shifted the 5-HT concentration-response curve to the right. 5-HT (3 × 10−6 M)-induced corporal relaxation was not affected by tetrodotoxin, ketanserin, granisetron or GR113808A. At 10−7 M, neither methysergide nor NAN-190 affected corporal relaxation, but at a high concentration (10−6 M) they both inhibited it and shifted the 5-HT concentration-response curve to the right. We conclude that 5-HT-induced antral contraction is mediated by cholinergic neurons via 5-HT2A, 5-HT3 and 5-HT4 receptors, whereas corporal relaxation is mediated via 5-HT1-like receptors on smooth muscle that are sensitive to methysergide and NAN-190.

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