EFFECTS OF MELATONIN IN ISOLATED RAT PAPILLARY-MUSCLE

Melatonin (N-acetyl-5-methoxytryptamine), the principal hormone of the vertebral pineal gland, elicits several neurobiological effects, Howe ver, the effects of melatonin on cardiac muscle are still unknown, The first goal of the study was to investigate the role of melatonin on m yocardial contractility in isolated rat papillary muscle using dose-re sponse curves to melatonin, to isoproterenol and calcium either in the presence or in the absence of melatonin (0.3 nM). Response curves to isoproterenol were additionally performed in the presence of melatonin plus the specific receptor antagonist N-acetyltryptamine (10 mu M); t he adenylate-cyclase stimulator forskolin (10 mu M) was also used, Mel atonin has no direct inotropic effect in isolated rat papillary muscle but counteracts isoproterenol but not [Ca2+] effects. In fact, the EC 50 for isoproterenol was significantly higher in the presence than in the absence of melatonin (p < 0.001), This anti-adrenergic action occu rs through an interaction to a specific cardiac receptor, Forskolin-st imulated adenylate cyclase induced an increase of contractile force (118 +/- 25%) which was reduced in the presence of melatonin (+26 +/- 1 0%; p < 0.01). In conclusion, we found that melatonin possess anti-adr energic effect in isolated rat papillary muscle, This phenomenon was a bolished in the presence of its receptor antagonist N-acetyl-tryptamin e demonstrating that melatonin operates through a specific cardiac rec eptor, The reduction of contractility increase, induced by forskolin-s timulated adenylate cyclase, shows that melatonin may act through a re duction of cyclic AMP accumulation. (C) 1997 Federation of European Bi ochemical Societies.