OBJECTIVE: Anti-ss-adrenergic actions of several substances influence heart function significantly. The anti-ss-adrenergic effect of melatonin was investigated, with special attention to protein kinase C (PKC) and nitric oxide (NO). DESIGN: Guinea pig papillary muscles were exposed to melatonin (500 pM) for 15 min and 20 min washout. Contractile force was measured during a bolus of isoproterenol (300 nM) given before melatonin, at the end of melatonin-exposure and after washout. In separate experiments blockers of PKC, NO-synthase (NOS) and melatonin receptors were added, or forskolin (10 microM) substituted for isoproterenol. RESULTS: Melatonin significantly reduced the increase in contractile force in response to isoproterenol, both when present and after melatonin-washout. The reduction was unaffected by inhibition of PKC, while inhibition of melatonin receptors or NOS seemed to abolish the effect. Melatonin induced a sustained but not acute reduction of contractile force response with forskolin stimulation. This was abolished by NOS-inhibition. CONCLUSION: Receptor-mediated immediate and sustained anti-ss-adrenergic effects of melatonin were demonstrated in contractile function. A role for NO in the response was indicated, while a role for PKC was not verified.
OBJECTIVE: Anti-ss-adrenergic actions of several substances influence heart function significantly. The anti-ss-adrenergic effect of melatonin was investigated, with special attention to protein kinase C (PKC) and nitric oxide (NO). DESIGN:Guinea pig papillary muscles were exposed to melatonin (500 pM) for 15 min and 20 min washout. Contractile force was measured during a bolus of isoproterenol (300 nM) given before melatonin, at the end of melatonin-exposure and after washout. In separate experiments blockers of PKC, NO-synthase (NOS) and melatonin receptors were added, or forskolin (10 microM) substituted for isoproterenol. RESULTS:Melatonin significantly reduced the increase in contractile force in response to isoproterenol, both when present and after melatonin-washout. The reduction was unaffected by inhibition of PKC, while inhibition of melatonin receptors or NOS seemed to abolish the effect. Melatonin induced a sustained but not acute reduction of contractile force response with forskolin stimulation. This was abolished by NOS-inhibition. CONCLUSION: Receptor-mediated immediate and sustained anti-ss-adrenergic effects of melatonin were demonstrated in contractile function. A role for NO in the response was indicated, while a role for PKC was not verified.