5-HT-induced colonic contractions: enteric locus of action and receptor subtypes.
The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and the receptor subtypes involved in the stimulation of in vivo phasic contractions in the colon were investigated by close intra-arterial infusions in conscious dogs. The contractile response to 5-HT was blocked completely by prior close intra-arterial infusion of atropine and reduced significantly by prior close intra-arterial infusions of tetrodotoxin and hexamethonium. The contractile response was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior close intra-arterial infusion of N omega-nitro-L-arginine methyl ester. Prior close intra-arterial infusions of 5-HT1A/5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4 receptor antagonists had no significant effect on the contractile response to 5-HT. By contrast, 5-HT3 receptor antagonist significantly and dose dependently inhibited the contractile response to 5-HT. We conclude that the in vivo phasic contractile response to 5-HT in the colon is mediated mainly by 5-HT3 receptors located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that use NO as a neurotransmitter.
Graf
S
S
Department of Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
Sarna
S K
SK
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D004285:Dogs; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology; D018738:Hexamethonium / Q000008:administration & dosage / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D008784:Methysergide / Q000008:administration & dosage / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology
D001285:Atropine; D017829:Granisetron; D018738:Hexamethonium; D008784:Methysergide; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D017294:Ondansetron; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D013779:Tetrodotoxin