MICROINJECTION OF DYNORPHIN INTO THE SUPRAOPTIC AND PARAVENTRICULAR NUCLEI PRODUCES ANTIDIURETIC EFFECTS THROUGH VASOPRESSIN RELEASE

The mechanisms for the antidiuretic effects of dynorphin (DYN), an end ogenous kappa-agonist, microinjected into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei were investigated. DYN decrease d the urine outflow rate dose-dependently from 5 to 20 nmol in the SON and PVN, and it increased vasopressin release. Microinjection of des- Tyr-DYN (a non-opioid peptide) into the SON produced antidiuretic effe cts with similar potency to that of the DYN-induced effects. However, in the PVN, the effects of des-Tyr-DYN were very markedly weaker than those of DYN. The DYN-induced antidiureses in the SON were partially i nhibited by phenoxybenzamine, timolol and atropine, but nob by naloxon e. Those in the PVN were partially inhibited by naloxone, timolol and atropine, but not by phenoxybenzamine. Synthetic specific kappa-agonis ts, U50,488H and ly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Arg-Leu-Arg-Gly 5- aminopentylamide (DAKLI), microinjected into the PVN also produced ant idiuretic effects in a dose-dependent manner. The order of antidiureti c potency was DAKLI> DYN> U50,488H, which was the same as that of kapp a-receptor binding affinity. The DAKLI-induced antidiureses in the PVN were not inhibited by naloxone. These results suggested that DYN caus ed antidiureses by vasopressin release, through adrenergic and choline rgic mechanisms in the SON and PVN. Only the DYN-induced effects in th e PVN were mediated, at least partially, through opioid receptors, per haps the kappa-subtype.