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 endogenous kappa-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 increased 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. Synthetic specific kappa-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-dependent manner. The order of antidiuretic potency was DAKLI > DYN > U50,488H, which was the same as that of kappa-receptor binding affinity. The DAKLI-induced antidiureses in the PVN were not inhibited by naloxone. 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 kappa-subtype.
Tsushima
H
H
Department of Pharmacology, Nagoya City University Medical School, Japan.
Mori
M
M
Matsuda
T
T
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000595:Amino Acid Sequence; D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009997:Osmotic Pressure / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000187:drug effects; D014554:Urination / Q000187:drug effects; D014667:Vasopressins / Q000378:metabolism*
D001337:Autonomic Agents; D010446:Peptide Fragments; D010455:Peptides; D011759:Pyrrolidines; C057337:dynorphin A-analogue kappa ligand; D014667:Vasopressins; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C082245:dynorphin (2-17)