ABSTRACT
Acetaminophen LD50 was two fold lower in female than male mice, the greater sensitivity of female mice for acetaminophen was also reflected in the serum enzyme levels of glutamic oxaloacetic and pyruvic transaminases (SGOT/SGPT), where the enhancement of both enzymes was higher in female than male mice. We could also observe the L-cysteine protection against the toxic effect of acetaminophen. Our results demonstrate that the lethal action of acetaminophen administrated either P.O. or S.C., is sex related.
Subject(s)
Acetaminophen/toxicity , Administration, Oral , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Cysteine/pharmacology , Female , Injections, Subcutaneous , Lethal Dose 50 , Male , Mice , Sex FactorsSubject(s)
Male , Female , Animals , Rats , Aspartate Aminotransferases , Alanine Transaminase , AcetaminophenSubject(s)
Calcium/pharmacology , Cerebral Aqueduct/drug effects , Endorphins/antagonists & inhibitors , Enkephalin, Methionine/analogs & derivatives , Morphine/antagonists & inhibitors , Animals , Enkephalins/antagonists & inhibitors , Male , Nociceptors/drug effects , Rats , Rats, Inbred Strains , beta-EndorphinABSTRACT
1 Morphine-theophylline interactions were investigated in both acute and narcotic-dependent preparations, in vitro and in vivo, using four different experimental models: LD50 doses of morphine and naloxone in the mouse; naloxone-induced contractions in the electrically-stimulated and opiate-dependent isolated ileum of the guinea-pig; naloxone-induced jumps in the mouse; an calcium uptake in synaptosomal preparations. 2 The LD50 of morphine was significantly increased by theophylline. 3 The lethal effect of theophylline was potentiated by pretreatment of the animals with naloxone. 4 Theophylline displayed protective effects in the inhibitory response to morphine and antagonism to the withdrawal response induced by naloxone in the electrically-stimulated isolated ileum of the guinea-pig. 5 The number of jumps induced by naloxone in morphine-dependent mice was significantly diminished by theophylline. 6 The inhibitory effect of morphine on the synaptosomal uptake of calcium was decreased by theophylline. 7 The effects of both morphine and theophylline on the cyclic nucleotides and the possible role of calcium in these actions are discussed.
Subject(s)
Morphine/pharmacology , Theophylline/pharmacology , Animals , Calcium/metabolism , Drug Interactions , Electric Stimulation , Guinea Pigs , Ileum/drug effects , In Vitro Techniques , Lethal Dose 50 , Mice , Motor Activity/drug effects , Naloxone/pharmacology , Synaptosomes/metabolismABSTRACT
The effect of morphine on the uptake of 45Ca++ was studied in lysed synaptosomes obtained from homogenates of whole mouse brain. The addition of morphine, 10(-6) M, to the incubation medium or acute administration of 10 or 20 mg/kg s.c. resulted in a decrease in 45Ca++ uptake; this decrease was observed only in the presence of ATP (3 mM). In contrast, after morphine pellet implantation (72 hr) to induce tolerance and physical dependence, an enhancement of lysed synaptosomal 45Ca++ uptake occurred; the increase was obtained in the presence but not in the absence of ATP. The enhancement of Ca++ uptake appears to be related with the degree of tolerance and dependence development since a linear relationship was noted between the time of morphine pellet implantation and the increase in 45Ca++ uptake by lysed synaptosomes. The acute inhibitory action on 45Ca++ uptake by morphine was prevented in vitro by naloxone, 1.9 x 10(-8) M, and in vivo by 2 mg/kg of naloxone s.c. and the chronic enhancing action of morphine by the simultaneous implantation of a naloxone pellet with the morphine pellet. The present findings lend further support to our previous reports in which we suggest that alterations in Ca++ flux may be involved with morphine analgesia, tolerance and physical dependence.
Subject(s)
Brain/metabolism , Calcium/metabolism , Morphine/pharmacology , Synaptosomes/metabolism , Animals , Biological Transport, Active/drug effects , Kinetics , Male , Mice , Naloxone/pharmacology , Synaptosomes/drug effectsABSTRACT
The uptake of 45Ca2+ by nerve-ending fractions from brains of mice was inhibited in vitro by 10(-9)M concentrations of beta-endorphin and in mice injected intraventricularly with 7 picomoles of beta-endorphin. That the effect was a specific opiate agonist response of beta-endorphin was demonstrated by use of the opiate antagonist, naloxone, which reversed the action. A role for beta-endorphin in the regulation of calcium flux and neurotransmitter release should be considered.
Subject(s)
Calcium/metabolism , Endorphins/pharmacology , Synaptosomes/drug effects , Animals , Biological Transport/drug effects , Dose-Response Relationship, Drug , Drug Tolerance , Endorphins/antagonists & inhibitors , Male , Mice , Naloxone/pharmacology , Neurotransmitter Agents/metabolism , Rats , Synaptosomes/metabolismABSTRACT
The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence.
