Melatonin enhances guanylate cyclase activity in a variety of tissues.

The objective of the present investigation was to determine if melatonin at physiological concentrations might have part of its mechanism of action through enhancement of guanylate cyclase (E.C.4.6.1.2) activity. Melatonin enhanced guanylate cyclase activity two-three fold in rat anterior pituitary, thyroid, testis, ovary, liver and small intestine at the 1 nanomolar concentration. Some stimulation of hepatic guanylate cyclase activity by melatonin was seen at concentrations as low as 1 picomolar. There was no stimulation of guanylate cyclase activity at concentrations below 1 picomolar. Maximal enhancement of guanylate cyclase activity was seen at the 1 nanomolar concentration of melatonin with no further enhancement being observed with increasing the concentration to the micromolar range. Thus, the data in the present investigation indicates that at concentrations at which melatonin is known to cause physiological effects, melatonin does cause an enhancement of the activity of the guanylate cyclase-cyclic GMP system.