Actions of serotonin antagonists on cholera-toxin-induced intestinal fluid secretion.
The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists were tested in rats in vivo on the intestinal fluid secretion evoked by cholera toxin. Five receptor antagonists were used, namely 2-bromolysergic acid diethylamine (2-bromo-LSD), granisetron, ketanserin, methysergide and ondansetron. The drugs were used in doses that inhibited the arterial hypertension and/or bradycardia evoked by 5-HT given i.v. Granisetron and ondansetron markedly diminished cholera-toxin-evoked secretion, whereas ketanserin was without any effect. Methysergide also diminished cholera-toxin-induced fluid secretion particularly when the drug was given as an i.v. infusion. The results are considered in relation to the pathophysiology of cholera secretion and to the current views of receptor subtypes for 5-HT. It is proposed that the receptor involved is a 5-HT3 receptor, possibly also a receptor of the 5-HT1 type. Results from experiments in which 5-HT (20 mM) was placed in the intestinal lumen to evoke an intestinal secretion suggest that the 5-HT3 receptor is located in the villus tissue. It was also demonstrated that zimeldine, an inhibitor of presynaptic 5-HT reuptake, diminished choleraic secretion, an effect that may be ascribed to a 5-HT tachyphylaxis caused by an accumulation of 5-HT in a synaptic cleft.
Department of Physiology, University of Göteborg, Sweden.
A
A
Sjöqvist
J
J
Cassuto
M
M
Jodal
O
O
Lundgren
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D005260:Female; D017829:Granisetron; D007093:Imidazoles / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D017294:Ondansetron; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D015031:Zimeldine / Q000494:pharmacology
D002772:Cholera Toxin; D017829:Granisetron; D007093:Imidazoles; D007191:Indazoles; D007650:Ketanserin; D008238:Lysergic Acid Diethylamide; D008784:Methysergide; D017294:Ondansetron; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015031:Zimeldine