Positive inotropic response to 5-HT in human atrial but not in ventricular heart muscle.
The effects of 5-hydroxytryptamine (5-HT) on force of contraction (FC), action potential (AP) and calcium current (ICa) were studied in human right atrial and left ventricular heart muscle. 5-HT exerted a concentration-dependent increase in FC in multicellular atrial preparations; the EC50 was approximately 3 x 10(-7) mol/l. Maximal increases in FC (252 +/- 58% of control values; mean +/- SEM, n = 6) were obtained at 5-HT 10(-5) mol/l. At this concentration, ICa was increased four- to sevenfold in enzymatically isolated atrial myocytes. In contrast, ventricular preparations did not respond to 5-HT; FC, AP and ICa remained unaffected. In the same preparations, FC was increased by isoprenaline three- to fourfold. These results confirm the observation that 5-HT induces a positive inotropic effect in the human atrium, possibly mediated by activation of the adenylyl cyclase - cyclic AMP system. Our study demonstrates, however, the complete lack of functional 5-HT receptors, with respect to changes in FC, in the human ventricle. Since the positive inotropic effect of 5-HT in the human heart is obviously restricted to the atrium, our findings question the concept of developing 5-HT receptor agonists for the treatment of heart failure.
Jahnel
U
U
Pharmakologisches Institut Universität Mainz, Federal Republic of Germany.
Rupp
J
J
Ertl
R
R
Nawrath
H
H
D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000502:physiology; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D010210:Papillary Muscles / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*
D015220:Calcium Channels; D012701:Serotonin; D007545:Isoproterenol