Does hypercalcaemia or calcium antagonism affect human melatonin secretion or renal excretion?

Patients with primary hyperparathyroidism have higher serum melatonin concentrations during active disease than after surgical cure. Whether this is caused by hypercalcaemia per se, increased parathyroid hormone secretion or other mechanisms is unknown. We decided to elucidate whether exogenous hypercalcaemia influences melatonin secretion. For this purpose, eight healthy volunteers were infused with calcium and saline on separate days and in random order (experiment A). Hypercalcaemia inhibited nocturnal melatonin secretion by 20% but left urinary melatonin excretion unaffected. If exogenous hypercalcaemia inhibits melatonin secretion, it is reasonable to assume that calcium channel blockers such as verapamil might have the opposite effect. This was investigated in experiment B, in which eight healthy subjects were treated on separate occasions with oral verapamil and placebo. Verapamil did not affect nocturnal melatonin secretion but increased melatonin excretion by 145%. As 6-sulphatoxy-melatonin is the main melatonin metabolite excreted by the kidneys, it was considered important to find out whether verapamil would also influence the excretion of 6-sulphatoxy-melatonin. This was investigated in experiment C, in which eight healthy volunteers were treated, on separate occasions, with oral verapamil and placebo. In this experiment also, verapamil increased urinary melatonin excretion significantly (by 67%), but left excretion of 6-sulphatoxy-melatonin unaffected. These findings imply that verapamil influences the renal and/or hepatic handling of melatonin.