Metergoline and Other Peipheral Serotonin Antagonists Inhibit Prolactin Secretion through Mechanisms Unrelated to Serotonin 1

Abstract

Summary

The mechanism through which metergoline and other peripheral serotonin receptor antagonists inhibit prolactin secretion was studied. Reserpine, an agent well known to deplete brain catecholamines and serotonin, increased the serum prolactin concentration in male rats. The concomitant injection metergoline completely prevented this increase in hormone level, suggesting that metergoline has a direct effect to inhibit secretion of the hormone. Direct addition of metergoline to pituitary glands incubated in vitro decrease the amount of prolactin secreted, confirming this suspicion. Haloperidol at the concentration used was without effect on prolactin secretion, but it completely blocked the metergoline-mediated inhibition of prolactin secretion. Similar effects were observed with methergine, a metabolite of methysergide, and with LSD. These data directly related to the finding that methysergide significantly decreased the in vivo prolactin secretion by a transplanted pituitary tumor. Simultaneous injection of haloperidol blocked the inhibitory action of methysergide. Similarly, the LSD-mediated inhibition of prolactin secretion in vitro was blocked by haloperidol. We conclude that the inhibiting action of metergoline and methysergide to inhibit prolactin secretion is exerted directly at the pituitary through the stimulation of a dopamine receptor.