[N-METHYL-TYR1, N-METHYL-ARG7-D-LEU8]-DYNORPHIN-A-(1-8) ETHYLAMIDE, A STABLE DYNORPHIN ANALOG, PRODUCES DIURESIS BY KAPPA-OPIATE RECEPTOR ACTIVATION IN THE RAT

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dc.contributor.authorSALAS, SP
dc.contributor.authorROBLERO, JS
dc.contributor.authorLOPEZ, LF
dc.contributor.authorTACHIBANA, S
dc.contributor.authorHUIDOBROTORO, JP
dc.date.accessioned2025-01-23T19:22:02Z
dc.date.available2025-01-23T19:22:02Z
dc.date.issued1992
dc.description.abstractThe i.v. administration of E-2078 {[N-methyl-Tyr1-N-methyl-Arg7-D-Leu8]-dynorphin-A-(1-8) ethylamide} to conscious animals in doses of 15, 50 or 200-mu-g/rat caused a dose-related diuretic response associated with a significant in crease in glomerular filtration rate (GFR) and in blood pressure. The overall excretion of Na+ was not modified by the opioid, whereas it reduced K+ output and its fractional excretion. Time course studies demonstrated that the increase in GFR and in blood pressure were transient and did not parallel the changes in urine outflow. Pretreatment of the animal with 1 mg/kg of naltrexone or of naloxone reduced the pressor response but did not reduce the renal action of E-2078. Doses of naltrexone 10 times larger (10 mg/kg) were required to attenuate the diuretic effect and abolish completely the changes in K+ excretion; however, the increase in GFR was not antagonized by 10 mg/kg of naltrexone. Consonant with the studies in conscious rats, perfusion of isolated rat kidneys with 0.2 to 1.8-mu-M E-2078 increased urine flow in a dose-dependent manner, and this effect was prevented by the simultaneous perfusion of 2-mu-M naltrexone with the peptide. In pentobarbital-anesthetized animals, E-2078 elicited a diuretic response that was not parallelled by changes in GFR or electrolyte excretion. In addition, E-2078 caused a long-lasting decrease in blood pressure which was blocked completely by pretreatment of the animal with 1 mg/kg of naltrexone. The diuretic effect of E-2078 was not modified by pretreatment of the animals with beta-funaltrexamine. Rats anesthetized with ether or halothane also showed a decrease in blood pressure after E-2078. Anesthesia with ether or halothane attenuated or anulled the pressor action of bremazocine or U-50,488, whereas barbiturate anesthesia resulted in a precipitous and prolonged hypotension. These results suggest that the stable dynorphin analog, E-2078, produces its effects on urinary excretion primarily via a kappa receptor mediated mechanism.
dc.fuente.origenWOS
dc.identifier.issn0022-3565
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/98943
dc.identifier.wosidWOS:A1992JN95700014
dc.issue.numero3
dc.language.isoen
dc.pagina.final984
dc.pagina.inicio979
dc.revistaJournal of pharmacology and experimental therapeutics
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.title[N-METHYL-TYR1, N-METHYL-ARG7-D-LEU8]-DYNORPHIN-A-(1-8) ETHYLAMIDE, A STABLE DYNORPHIN ANALOG, PRODUCES DIURESIS BY KAPPA-OPIATE RECEPTOR ACTIVATION IN THE RAT
dc.typeartículo
dc.volumen262
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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