Browsing by Author "LOPEZ, LF"

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    KAPPA-OPIATE-INDUCED DIURESIS AND CHANGES IN BLOOD-PRESSURE - DEMONSTRATION OF RECEPTOR STEREOSELECTIVITY USING (+)-TIFLUADOM AND (-)-TIFLUADOM
    (1987) URETA, H; LOPEZ, LF; PEREZ, A; HUIDOBROTORO, JP
    (+)-Tifluadom injected i.p. produced a biphasic response of urine output: within the first hour of its administration the drug produced antidiuresis followed by a diuretic phase. In contrast, the (-) isomer produced a modest reduction in urine output as compared to the output of the saline-treated rats. In addition, (+)-tifluadom markedly reduced the output of urinary Na+ and K+. The effects of (+)-tifluadom were blocked by 7.5 mg/kg naloxone but not by 10 mg/kg of the benzodiazepine antagonist Ro 15-1788. Parallel experiments demonstrated that the i.v. administration of (+)-tifluadom to non-anesthetized rats caused a dose-related pressor response that lasted for at least 15 min. This effect of (+)-tifluadom wa blocked and antagonized by naloxone. In contrast, (-)-tifluadom was either inactive on the cardiovascular system or produced short-lasting hypotension. In pentobarbital-anesthetized rats, 100 .mu.g/kg (+)-tifluadom caused a precipitous hypotension that was reversed by naloxone but not by Ro 15-1788.
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    [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
    (1992) SALAS, SP; ROBLERO, JS; LOPEZ, LF; TACHIBANA, S; HUIDOBROTORO, JP
    The 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.
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