Summary
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 × 10−7 mol/l. Maximal increases in FC (252±58% of control values; means ± 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.
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Correspondence to: H. Nawrath at the above address
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Jahnel, U., Rupp, J., Ertl, R. et al. Positive inotropic response to 5-HT in human atrial but not in ventricular heart muscle. Naunyn-Schmiedeberg's Arch Pharmacol 346, 482–485 (1992). https://doi.org/10.1007/BF00169000
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DOI: https://doi.org/10.1007/BF00169000