AN ENKEPHALINERGIC MECHANISM FOR THE HYPOTHALAMIC EFFECT OF ATRIAL-NATRIURETIC-PEPTIDE TO INHIBIT LUTEINIZING-HORMONE SECRETION

Previous studies have demonstrated a hypothalamic site of action of atrial natriuretic peptide (ANP) to inhibit luteinizing hormone and an opioid mechanism has been suggested. We have identified the paraventricular nucleus as at least one locus of action of ANP since site-specific injection of 0.1 nmol, bilaterally into this nucleus, but not the medial preoptic nuclei or arcuate nucleus, resulted in a significant inhibition of plasma levels in conscious, ovariectomized rats 90 and 120 min later. This paraventricular site of action suggested an involvement of endogenous enkephalins. The stable enkephalin analog, [D-Pen2,5]enkephalin, when injected into the third ventricle in a dose of 1.0 nmol, produced a significant and transient inhibition of luteinizing hormone secretion similar to that seen following injection of 2.0 nmol ANP. Pretreatment of the rats 15 min before peptide injection with the selective delta opioid antagonist naltrindole (50-mu-g/2 ul saline) completely prevented the luteinizing hormone-inhibiting effects of both ANP and the enkephalin analog. Delta opioid blockade failed to prevent the prolactin-inhibiting effect of ANP but did reverse the prolactin-stimulating effect of [D-Pen2,5]enkephalin. Our results suggest a paraventricular nucleus site of action of ANP in addition to probable effects in the median eminence and indicate the possible enkephalinergic mediation of the peptide's ability to inhibit luteinizing hormone secretion.