Pharmacological characterization of 5-hydroxytryptamine-induced motor activity (in vitro) in the guinea pig gastric antrum and corpus.
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-1 H-indole-3-carboxylate maleate salt (GRl13808A), but neither 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190) nor N2-[(4R)-4-hydroxy-1-(1-methyl-1 H-indol-3-yl)carbonyl-L-prolyl]-N- methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide (FK888), inhibited 5-HT (3 x 10(-6) M: submaximal concentration)-induced antral contractions concentration dependently and shifted the 5-HT concentration-response curve to the right. 5-HT (3 x 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.
Tamura
T
T
Gastrointestinal Research Laboratory, Gunma University, Maebashi, Japan.
Sano
I
I
Satoh
M
M
Mizumoto
A
A
Itoh
Z
Z
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D011706:Pyloric Antrum / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000502:physiology
D012702:Serotonin Antagonists; D012701:Serotonin