ABSTRACT-The mechanisms for the antidiuretic effects of dynorphin (DYN), an endogenous K-agonist, microinjected into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei were investigated. DYN decreased the urine outflow rate dose-dependently from 5 to 20 nmol in the SON and PVN, and it in creased vasopressin release. Microinjection of des-Tyr-DYN (a non-opioid peptide) into the SON produced antidiuretic effects 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 inhibited by phenoxybenzamine, timolol and atropine, but not by naloxone. Those in the PVN were partially inhibited by naloxone, timolol and atropine, but not by phenoxybenzamine. Syn thetic specific K-agonists, U50,488H and Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Arg-Leu-Arg-Gly 5 aminopentylamide (DAKLI), microinjected into the PVN also produced antidiuretic effects in a dose-de pendent manner. The order of antidiuretic potency was DAKLI > DYN > U50,488H, which was the same as that of K-receptor binding affinity. The DAKLI-induced antidiureses in the PVN were not inhibited by nalox one. These results suggested that DYN caused antidiureses by vasopressin release, through adrenergic and cholinergic mechanisms in the SON and PVN. Only the DYN-induced effects in the PVN were mediated, at least partially, through opioid receptors, perhaps the x-subtype. Immunohistochemical studies show the presence of fibers and terminals of opioid neurons (1-3) in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. Also, cell bodies of vasopressin-containing neurons are localized in these nuclei. Numerous reports suggest that opioid neurons in the hypothalamus, the SON or PVN regulate the urine outflow rate. Intra cerebroventricular injection and microinjection into the nuclei of p and o-opioid agonists decrease the urine outflow rate (4 8). These antidiuretic effects, at least in part, appear to be induced by increased vasopressin re lease, although there are some reports that the opioid agonists show decrease or have no effect on the firing rate of vasopressin-containing neurons or vasopressin release (4, 9-13). On the other hand, c-agonists injected into the ventricle decrease vasopressin release and induce diuretic effects (14-16). Systemic administered K-agonists also elic it the same effects, which are suggested to be mediated through K-receptors on the neurohypophysis (16-19).In our preliminary study, however, microinjection of dynorphin(1-13) (DYN), an endogenous K-agonist (20, 21) which co-exists with vasopressin (22), into the SON and PVN decreased the urine outflow rate (23). Thus, we investigated the mechanisms of the DYN-induced anti diuretic effects in this study.
MATERIALS AND METHODSMale Wistar rats (280-330 g), starved overnight but allowed free access to water, were used. They were orally loaded with tap water (5 ml/100 g body weight); and 45 min later, they were anesthetize...