Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is frequently hypothesized that drug-induced alterations in the density of beta-adrenergic receptors underlie tolerance to and physical dependence on agonists and antagonists at beta-adrenergic receptors. Two approaches to determining the effect of treatment with drugs on the density of beta-adrenergic receptors are described. In the first, the density of beta-adrenergic receptors was measured on leukocytes taken from human subjects during and after drug treatment. Treatment with the antagonist propranolol caused an increase in the density of beta-adrenergic receptors on leukocytes, whereas treatment with the agonists terbutaline and ephedrine, or pindolol, an antagonist with intrinsic sympathomimetic activity, caused a decrease in the density of beta-adrenergic receptors. In the second approach, the effect of agonists on the density of beta-adrenergic receptors on C6 glioma cells in culture was determined. Incubation with the full agonist isoproterenol decreased the density of both beta 1- and beta 2-adrenergic receptors. In contrast, incubation with pindolol or celiprolol, also an antagonist with intrinsic sympathomimetic activity, selectively decreased the density of beta 2-adrenergic receptors. Pindolol and celiprolol may be useful in situations in which selective stimulation of beta 2-adrenergic receptors and blockade of beta 1-adrenergic receptors is desirable.
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PMID:Effects of chronic administration of agonists and antagonists on the density of beta-adrenergic receptors. 287 41

The molecular mechanisms associated with ethanol-induced tolerance and physical dependence have yet to be elucidated. In previous studies we have demonstrated that chronic ethanol administration produced a decrease in the GABAA receptor mRNA level of alpha 1, alpha 2, alpha 5 subunits, and a decrease in the polypeptide (alpha 1, alpha 2, and alpha 3) expression in the rat cerebral cortex. In this study we examined the effect of chronic ethanol treatment on the mRNA levels and the expressions of the beta-subunits of the GABAA receptors in rat cerebral cortex. The results indicate that chronic ethanol administration produced an upregulation of the beta 1 subunit mRNA (12 kb) by 29 +/- 10%, beta 2 mRNA (8 kb) by 55 +/- 6% and the beta 3-subunit (6 kb) mRNA by 72 +/- 9% in cerebral cortex. The levels of the beta 2 and beta 3 subunit mRNAs remains elevated at 24 hr withdrawal. We also investigated the effect of chronic ethanol administration on the beta-subunit polypeptide expression using monoclonal antibody BD17, which recognizes the beta 2 (P56) and beta 3 (P58) polypeptides. Chronic ethanol treatment increased the levels of both of these polypeptides in cerebral cortex. Taken together, chronic ethanol administration produced an upregulation of the beta-subunit mRNA and the polypeptide expression of these subunits in rat cerebral cortex. In contrast, chronic ethanol treatment decreased the expression of various alpha-subunits in the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic ethanol treatment upregulates the GABA receptor beta subunit expression. 805 81

The benzodiazepine (BZ), triazolam (TRZ), results in tolerance and physical dependence. We performed in situ hybridization (ISH) experiments to gain a more complete understanding of the processes involved in mediating the effects of chronic TRZ ISH allowed us to determine whether GABAA receptor subunit mRNAs are affected by 4 weeks of TRZ administration and its withdrawal and to localize the changes to discrete brain regions. Using oligonucleotide probes directed toward the alpha 1-6, beta 1-3, and delta subunit mRNAs, we analyzed message density in 63 brain regions of TRZ-treated and control rat brains, alpha 1-4, beta 1-3, and delta subunit mRNA levels were altered by 28 days of chronic TRZ. No changes were noted in alpha 5-6 mRNA levels. Many of the changes measured were localized to neural structures within the limbic circuit of Papez, or in close communication with this pathway. After a 24 h withdrawal period from 4 weeks of TRZ treatment, the changes noted on the 28th day of treatment were reversed. Moreover, brain regions that were unaffected by the 4-week treatment were altered by the 24 h withdrawal. Our results indicate that chronic treatment and withdrawal are associated with separate processes and that chronic TRZ is correlated with limbic alterations which may be responsible for some of its chronic effects.
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PMID:Chronic triazolam and its withdrawal alters GABAA receptor subunit mRNA levels: an in situ hybridization study. 903 26