Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to ascertain whether opiate receptors and brain enkephalins or endorphins are involved in pentobarbital anesthesia and toxicity, the effects of 1) two pure narcotic antagonists, naloxone and naltrexone, 2) morphine sulfate, 3) D-phenylalanine, an inhibitor of carboxypeptidase A, and 4) D-leucine, an inhibitor of leucineaminopeptidase, in combination with D-phenylalanine, were studied in mice. Both naloxone and naltrexone, (1, 5 and 10 mg/kg) administered subcutaneously to mice were unable to modify the duration of anesthesia when they were injected 5 min prior to a challenge dose (75 mg/kg) of pentobarbital (ip). The onset of anesthesia was unaltered by naloxone (1, 5 and 10 mg/kg) and naltrexone (1 mg/kg). Higher doses of naltrexone (5 and 10 mg/kg) delayed the onset of anesthesia slightly. Morphine (1, 2.5 and 5 mg/kg) given 30 min before pentobarbital did not modify the onset or the duration of anesthesia. D-Phenylalanine (250 mg/kg), and D-phenylalanine + D-leucine (250 mg/kg each) injected ip an hour before pentobarbital did not affect either onset or duration of anesthesia. Naltrexone (10 mg/kg, ip) given 5 min before pentobarbital did not alter the LD50 of the latter. The studies do not support a role of enkephalins or endorphins in pentobarbital anesthesia or toxicity, and suggest a need for caution in using narcotic antagonists in treating pentobarbital toxicity.
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PMID:Studies of the possible role of brain endorphins in pentobarbital anesthesia and toxicity in mice. 49 53

The effect of D-Phenylalanine (D-Phe), putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in incubation mixture (up to 10(-3) mol/l) the hydrolysis of exogenous 3H-Met5-and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that that pharmacological activity of D-Phe is not directly related to the endogenous opiate system.
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PMID:The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome. 376 85