Effects of Opioid Peptides on Aldosterone Production: Stimulatory Effect of Leu-Enkephalin*

The effects of several opioid peptides (Leu-enkephalin, Met-enkephalin, D-Ala2,D-Leu5-enkephalin, and peptide E) on aldosterone secretion have been studied in isolated bovine adrenal glomerulosa cells. Leu-enkephalin significantly increased aldosterone production in a dose-dependent manner (10(-10)-10(-7) M). Similar results on steroidogenesis were obtained with the synthetic opioid D-Ala2,D-Leu5-enkephalin, whereas much higher concentrations of Met-enkephalin were required. Peptide E did not affect steroidogenesis. Naltrexone or naloxone (10(-5) M) potentiated the effect of Leu-enkephalin on aldosterone secretion. The effect of a general opioid antagonist (diprenorphine) or an agonist (etorphine) was also studied. The stimulation by Leu-enkephalin of aldosterone secretion was only partially blocked by diprenorphine. Etorphine (10(-6) and 10(-8) M) had no effect on basal steroidogenesis. It is proposed that the stimulatory effect of Leu-enkephalin on aldosterone production could be mediated by a different receptor than the classical opioid receptors presently known.