Effects of the enkephalin analog (D-Met2,Pro5)-enkephalinamide on alpha-melanocyte-stimulating hormone secretion

We used the met-enkephalin analog (D-Met2,Pro5)-enkephalinamide (DMPEA) to investigate enkephalinergic control of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion. Systemic (s.c.) administration of DMPEA elevated plasma titers of alpha-MSH in a dose- and time-related manner. Pretreatment with the opiate antagonist naltrexone had no effect on basal plasma levels of alpha-MSH but blocked DMPEA-induced alpha-MSH release. Treatment with a dose of naltrexone sufficient to block DMPEA-induced secretion of alpha-MSH had no effect on stress-induced secretion of alpha-MSH. Although pretreatment with the dopamine receptor agonist apomorphine prevented DMPEA-induced alpha-MSH secretion, DMPEA had no effect on the synthetic activity of tuberohypophysial dopamine neurons as gauged by measuring the accumulation of 3,4-dihydroxyphenylalanine in the neurointermediate lobe (NIL) following administration of NSD-1015. In vitro treatment of isolated NILs with DMPEA resulted in a significant increase in alpha-MSH release. Naltrexone completely blocked the stimulatory effects of DMPEA on alpha-MSH release in vitro. Our results indicate that DMPEA stimulates alpha-MSH secretion by acting directly through opiate receptors at the level of the NIL.