Browsing by Author "HUIDOBRO, F"

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    CENTRAL EFFECTS OF MORPHINE, LEVORPHANOL, ( - )-METHADONE AND THE OPIOID-LIKE PEPTIDES BETA-ENDORPHIN AND D-ALANINE2-METHIONINE ENKEPHALINAMIDE ON URINE VOLUME OUTFLOW AND ELECTROLYTES
    (1981) HUIDOBROTORO, JP; HUIDOBRO, F
    The intraventricular injection of 10-30 nmol of morphine, (-)-methadone or levorphanol caused a reduction in the volume of the urine output in rats previously hydrated with 0.5% NaCl. The decrease in urine outflow was associated with a dose-dependent reduction in the concentration of urine Na+ and K+. Two opioid-like peptides: .beta.-endorphin and D-alanine2 methionine enkephalinamide shared this morphine action. On a molar basis, .beta.-endorphin was about 100 times more potent than morphine to cause an equivalent antidiuresis. Naloxone injected i.p. antagonized the response of centrally administered morphine or .beta.-endorphin on urine formation and composition. (+)-Methadone or dextrorphan injected into the cerebral ventricles were considerably less active than their corresponding stereoisomers. N-methyl morphine injected i.p. was completely inactive up to doses that caused signs of toxicity; when injected into the lateral cerebral ventricles, it produced a decrease in the urine outflow and a reduction in the concentration of urine electrolytes. The pattern of changes in urine electrolytes produced by morphine and surrogates as well as the opioid-like peptides was in marked contrast to that caused by the i.p. administration of vasopressin. Whereas the i.p. administration of antidiuretic hormone caused oliguria and a large increase in the urine concentration of Na+ and K+, all the opiates produced at comparable antidiuresis a marked reduction in urine electrolytes. The opiates and the opioid-like peptides may selectively activate central opiate receptors to produce changes in urine formation and composition. Results are discussed in relation to probable central opiate mechanisms controlling the production and formation of urine.
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    DEVELOPMENT OF TOLERANCE TO THE EXCITATORY EFFECT OF MORPHINE AND CROSS-TOLERANCE TO THE INHIBITORY-ACTION OF BETA-ENDORPHIN IN THE ISOLATED RAT VAS-DEFERENS
    (1981) HUIDOBROTORO, JP; MIRANDA, H; HUIDOBRO, F
    In the isolated rat vas deferens, morphine caused an increase in the neuromuscular twitch evoked by electrical stimulation. In rats chronically treated with morphine, the concentration of the opiate required to cause a 50% increase in the twitch was about 3 times larger than needed to elicit the same response in vasa from rats treated with a placebo. The simultaneous administration of naloxone plus morphine partially antagonized tolerance development by about 22%. Morphine tolerance was extended to other opiate-like alkaloids such as etonitazene and a derivative of azidomorphine (CAM). In contrast to the effects of morphine, .beta.-endorphin inhibited neuromuscular transmission. Vasa from rats chronically treated with morphine were about 10 times less sensitive to the inhibitory effect of .beta.-endorphin as compared to paired placebo-treated controls. Chronic naloxone treatment in conjunction with morphine significantly reduced the cross-opiate tolerance by 66%. Morphine may interact at 2 different sites in the nerve terminals of the rat vas deferens.
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    EFFECT OF MORPHINE ON THE CLEARANCE OF ENDOGENOUS CREATININE AND BLOOD CLINICAL CHEMICALS IN THE RAT
    (1979) HUIDOBRO, F; CROXATTO, R; HUIDOBROTORO, JP
    The effect of morphine on urine and blood serum concentration of Na+, K+, Cl- and other chemicals was determined using Sprague Dawley rats, previously hydrated with 50 ml/kg of 0.5% NaCl to provoke an increased diuresis. Morphine caused about a 90% decrease in the urine concentration of Na+, K+ and Cl-. This reduction in the urine electrolyte excretion was associated with a small but significant increase in the concentration of the blood Na+ and Cl-. The anti-diuresis and the decrease in urine electrolytes caused by morphine was paralleled by a 50% reduction of the endogenous creatinine clearance. An acute dose of 7.5 mg/kg morphine i.p. did not alter the concentration of 13 other clinical blood chemicals with the exception of urea. After 18 h of morphine pellet implantation, a significant increase was found in the blood urea and in the activity of serum transaminases. Lactic dehydrogenases isoenzymes 1 and 2 were significantly increased in the blood of rats chronically administered with morphine.
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    EFFECTS OF BETA-ENDORPHIN AND D-ALANINE2 ENKEPHALINAMIDE ON URINE PRODUCTION AND URINARY ELECTROLYTES IN THE RAT
    (1979) HUIDOBROTORO, JP; HUIDOBRO, F; CROXATTO, R
    The intracerebro-ventricular administration of human .beta.-Endorphin (.beta.-EP, 0.1-3 .mu.g/rat) or D-alanine2 methionine enkephalinamide (D-ala, 0.3-30 .mu.g/rat) caused a dose dependent reduction in urine volume. The oliguria was associated with a decrease in the concentration of Na+ and K+ in the urine of rats previously hydrated by oral administration with 25 ml/kg tap water plus 50 ml/kg 0.5% NaCl. On a molar basis, .beta.-EP proved to be about 5-7 times more potent than D-ala. The effects caused by the peptides were antagonized by simultaneous i.p. administration of 1 mg/kg naloxone. In rats treated chronically with morphine, no cross-tolerance was demonstrated to the antidiuretic effect of .beta.-EP, but clear cross-tolerance was evident to the changes in urine electrolytes induced by .beta.-EP. Morphine and the opiate peptides may share a similar mechanism of action.
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    EVIDENCE FOR MORPHINE AND MORPHINE-LIKE ALKALOID RESPONSES RESISTANT TO NALOXONE BLOCKADE IN THE RAT VAS-DEFERENS
    (1979) MIRANDA, H; HUIDOBRO, F; HUIDOBROTORO, JP
    The application of morphine or surrogates to the isolated rat was deferens maintained at 37.degree. C in Tyrode solution produced an increase in the electrically induced muscular twitch. Leucine enkephal in or D-2-D-Ala-Met enkephalinamide produced a dose-dependent inhibition of the muscular twitch. The effect of morphine and derivatives was not antagonized by naloxone, but the depression caused by the opiate pentapeptides or .beta.-endorphin was readily antagonized and reversed by naloxone. Tolerance developed to the in vitro effect of morphine; vasa deferentia obtained from tolerant-dependent rats were about 6 .times. less sensitive to the effect of morphine and about 5 .times. less sensitive to the depression caused by leucine enkephalin as compared to their respective paired, placebo implanted control rats.
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    INTERACTIONS BETWEEN MORPHINE AND THE OPIOID-LIKE PEPTIDES IN THE RAT VAS-DEFERENS
    (1980) HUIDOBRO, F; HUIDOBROTORO, JP; MIRANDA, H
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    N-CHLOROACETYL 5-METHOXYTRYPTAMINE (ISAMIDE) - SELECTIVE ANTAGONIST OF 5-HYDROXYTRYPTAMINE IN THE RAT UTERUS
    (1979) HUIDOBROTORO, JP; HUIDOBRO, F; RUIZ, M
    Isamide, the N-chloracetyl derivative of 5-methoxytryptamine, produced a dose-dependent competitive blockade of uterine contractions in vitro induced by 5-HT [hydroxytryptamine]. The pA2 value for the 5-HT-isamide interaction was 4.42. The blockade was short-lasting and reversible; after recovery, a dose-dependent increase in the uterine sensitivity to 5-HT was found. The blockade was selective to the 5-HT receptor. The simultaneous application of 5-HT plus isamide partially prevented the 5-HT-induced auto blockade phenomenon. In addition, isamide did not affect the contractile responses of the uterus to oxytocin or bradykinin or the contractile effects of the rat vas deferens to adrenaline.
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    NON-COMPETITIVE-NON-EQUILIBRIUM ALPHA-ADRENOCEPTOR BLOCKING PROPERTIES OF N-BENZYL IODOACETAMIDE, BETSAMIDE
    (1979) HUIDOBROTORO, JP; HUIDOBRO, F; MIRANDA, H
    N-Benzyl iodoacetamide, betsamide, at 10 mg/kg i.v. blocked the hypertensive and contractile responses of the nictitating membrane of the cat to adrenaline [epinephrine]. The blockade had a lag period before full development. Pretreatment of cats with betsamide for 7 or 18 h showed a non-equilibrium type of .alpha.-adrenoceptor blockade. The responses of the nictitating membrane to adrenaline were markedly depressed and did not recover after high doses of adrenaline. In the same cats, adrenaline caused a profound hypotension. The effect of betsamide lasted for at least 72 h. In the rat isolated vas deferens, 3 .times. 10-5 M betsamide non-competitively blocked the contractile responses to noradrenaline [norepinephrine], the adrenoceptor blockade was less effective when betsamide was applied with noradrenaline. The blockade lasted for > 24 h and was not reversible after extensive washing. Betsamide antagonized the contractile effects of the guinea pig trachea to adrenaline and isoprenaline. Results are discussed in relation to a probable mechanism of action.
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    STUDIES ON TOLERANCE DEVELOPMENT TO SINGLE DOSES OF MORPHINE IN MICE
    (1976) HUIDOBRO, F; HUIDOBROTORO, JP; WAY, EL
    Single-dose tolerance to the antinociceptive effect of morphine can be demonstrated using an adequate initial priming dose of morphine and allowing an interval of 48-72 h for its development. The threshold does necessary to produce tolerance was about 3-4 times greater than that for producing analgesia but higher doses of morphine did not enhance further tolerance development. Evidence of tolerance was indicated by the fact that when the antinociceptive response to morphine was assessed by the hot-plate and the tail-flick procedures, a shift in the dose-response curve of morphine to the right occurred after an adequate single priming dose of morphine. Cross-tolerance was evidenced by a decrease in analgetic response to methadone 3 days after a single priming dose of morphine and a decrease in morphine response after a single dose of methadone. The development of single-dose tolerance was inhibited by cycloheximide. Single-dose tolerance was also blocked by 5,6-dihydroxytryptamine and perhaps enhanced by L-tryptophan. Cyclic AMP did not affect single-dose tolerance development significantly although the direction was in favor of augmentation. Morphine uptake by the brain was not modified by the development of single-dose tolerance. Physical dependence, as measured by naloxone-precipitated withdrawal jumping, was not observed when single-dose analgetic tolerance was maximal. Single-dose tolerance to morphine apparently involves the synthesis of some marcomolecule, thus supporting previous findings in this laboratory involving as association with serotonin (5-hydroxytryptamine).