Antidiuretic effects of methionine-enkephalin and 2-D-alanine-5-methionine-enkephalinamide microinjected into the hypothalamic supraoptic and paraventricular nuclei in a water-loaded and ethanol-anesthetized rat.

Effects of methionine-enkephalin (ME) and 2-D-alanine-5-methionine-enkephalinamide (DAMEA) microinjected into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, which contain neurons synthesizing and releasing antidiuretic hormone, upon the outflow and the osmotic pressure of urine and the other visceral functions were studied in a rat which was loaded with water and anesthetized with ethanol. These opioid peptides when microinjected into the SON or PVN induced potent antidiuretic effects in dose-dependent and time-dependent manners with no significant effects on the other visceral functions. The approx. ED50 values for DAMEA were 1.3 (in the SON) and 0.7 (in the PVN) nmol, and the values for ME were 110 (in the SON) and 60 (in the PVN) nmol. The antidiuretic effects showed slow onset and long duration, with a minimal urine outflow at approx. 0.5 hr after microinjection and an approx. 2 hr-duration. The effects induced by the opioid peptides were inhibited by pretreatment with naloxone or atropine, without effects of pretreatment with alpha- or beta-adrenoceptor antagonists, suggesting that the antidiuretic effects were mediated through an opioid receptor having low sensitivity to naloxone and also possibly mediated through a muscarinic receptor which was stimulated probably by the ACh released by the opioid peptides.