Receptor mechanisms involved in the 5-HT-induced inotropic action in the rat isolated atrium.
1. The effects of 5-hydroxytryptamine (5-HT) in rat cardiac preparations were studied. 5-HT up to 10 microM failed to affect contractility in papillary muscles. However, in electrically driven (1 Hz) left atria 5-HT exerted a positive inotropic effect that started at 1 microM and attained its maximum at 10 microM (312+/-50% of predrug value, n=8). 2. 5-HT 10 microM stimulated the content of inositol-1,4,5-trisphosphate but not of cyclic AMP in rat left atria. 3. Plasma and serum levels of 5-HT amounted to about 0.3 microM and 15 microM, respectively. 4. The selective 5-HT4 receptor antagonists GR 125487 (10 nM and 1 microM) and SB 203186 (1 microM) did not attenuate the positive inotropic effect of 5-HT in rat left atria. In contrast, the 5-HT2 receptor antagonist ketanserin (5 nM, 50 nM, 1 microM) resulted in a concentration-dependent diminution of the positive inotropic effect of 5-HT in rat left atria. 5. Reverse transcriptase polymerase chain reaction with specific primers detected mRNA of the 5-HT2A receptor in rat atria and ventricles, while expression of the 5-HT4 receptor was confined to atria. 6. It is suggested that the positive inotropic effect of 5-HT in electrically driven rat left atria is mediated by ketanserin-sensitive 5-HT2A receptors and not through 5-HT4 receptors.
Läer
S
S
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, F.R.G.
Remmers
F
F
Scholz
H
H
Stein
B
B
Müller
F U
FU
Neumann
J
J
D000818:Animals; D016275:Atrial Function; D015139:Blotting, Southern; D000242:Cyclic AMP / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000235:genetics; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000097:blood / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D007211:Indoles; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; C082871:GR 113808