Effects of two enkephalin analogues, morphine sulphate, dopamine and naloxone on prolactin secretion from rat anterior pituitary glands in vitro.

Experiments were carried out on the antagonistic effects of opiates on the inhibition by dopamine of prolactin secretion from rat anterior pituitary glands. Dose-response and time-course experiments were carried out using both static incubation of paired hemipituitary glands and perifusion of whole glands. Dopamine (10-1000 nmol/l) was found to have an inhibitory effect on prolactin secretion, but at a lower concentration (0.1 nmol/l) a small stimulation was observed. Against an inhibition established with 100 nmol dopamine/l in static incubation, the three opiates under study, morphine sulphate, Leu5-enkephalin and D-Ala2,Met5-enkephalin (DAME), had a maximum antagonistic effect at 50-1000 nmol/l in a 90-min incubation. Morphine and DAME were rather more effective than Leu5-enkephalin, possibly because of degradation of the latter. Naloxone reversed the effect of morphine. All three opiates showed little effect on dopamine-inhibited prolactin secretion in a perifusion system. The data accord with previous suggestions that prolactin secretion may be stimulated both by very low concentrations of dopamine and by opiates acting to reverse the inhibition exerted by higher dopamine concentrations. It should be noted that both morphine and the enkephalins have similar effects on prolactin secretion, despite their normal specificity for different opiate receptors; their actions on the pituitary may thus be rather non-specific.