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. However, the effects of melatonin on cardiac muscle are still unknown. The first goal of the study was to investigate the role of melatonin on myocardial contractility in isolated rat papillary muscle using dose-response 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 microM); the adenylate-cyclase stimulator forskolin (10 microM) was also used. Melatonin has no direct inotropic effect in isolated rat papillary muscle but counteracts isoproterenol but not [Ca2+] effects. In fact, the EC50 for isoproterenol was significantly higher in the presence than in the absence of melatonin (p < 0.001). This anti-adrenergic action occurs through an interaction to a specific cardiac receptor. Forskolin-stimulated adenylate cyclase induced an increase of contractile force (+118 +/- 25%) which was reduced in the presence of melatonin (+26 +/- 10%; p < 0.01). In conclusion, we found that melatonin possess anti-adrenergic effect in isolated rat papillary muscle. This phenomenon was abolished in the presence of its receptor antagonist N-acetyl-tryptamine demonstrating that melatonin operates through a specific cardiac receptor. The reduction of contractility increase, induced by forskolin-stimulated adenylate cyclase, shows that melatonin may act through a reduction of cyclic AMP accumulation.
Abete
P
P
Cattedra di Geriatria, Istituto di Medicina Interna Cardiologia e Chirurgia Cardiovascolare Federico II, University of Naples, Italy.
Bianco
S
S
Calabrese
C
C
Napoli
C
C
Cacciatore
F
F
Ferrara
N
N
Rengo
F
F
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008550:Melatonin; D007545:Isoproterenol; D002118:Calcium