Piglet sinoatrial 5-HT receptors resemble human atrial 5-HT4-like receptors.
5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and the gastrointestinal kinetic benzamides renzapride and cisapride caused tachycardia in spontaneously beating right atria of piglet in the presence of 400 nmol/l (+/-)-propranolol and 6 mumol/l cocaine. The maximum tachycardia caused by agonists, compared to that evoked by 200 mumol/l (-)-isoprenaline, was 63% for 5-HT, 50% for 5-CT, 50% for renzapride and 28% for cisapride. The rank order of potency was 5-HT greater than renzapride greater than cisapride greater than 5-CT. The effects of the agonists, but not those of (-)-isoprenaline, were antagonised by 3 alpha-tropanyl-1H-indole-3-carboxylic acid (ICS 205930); the pKB of ICS 205930 (vs 5-HT) was 6.9. These characteristics suggest that piglet sinoatrial 5-HT receptors are similar to "so-called" 5-HT4 receptors previously described in mouse colliculi neurons. Piglet sinoatrial 5-HT4-like receptors resemble the human atrial 5-HT receptors that mediate positive inotropic effects of 5-HT.
Kaumann
A J
AJ
Smith Kline Beecham Pharmaceuticals, Frythe, Welwyn, Hertfordshire, UK.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002316:Cardiotonic Agents / Q000494:pharmacology; D020117:Cisapride; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000145:classification* / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects*; D013552:Swine; D000077526:Tropisetron
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002316:Cardiotonic Agents; D007211:Indoles; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000077526:Tropisetron; C053006:renzapride; C047087:5-carboxamidotryptamine; D020117:Cisapride