Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous work showed that chronic ethanol ingestion by C57BL mice resulted in reduced stimulation of cerebral cortical adenylate cyclase (AC) activity by isoproterenol (ISO) and guanine nucleotides (GN). To investigate the mechanism of this change we have assessed the effect of chronic ethanol ingestion on agonist and antagonist binding to BAR in cerebral cortex (mainly beta 1-AR) and cerebellum (mainly beta 2-AR). C57BL mice were fed ethanol in a liquid diet for seven days and were withdrawn for various intervals. Agonist (ISO) binding data were best fit by a two-site model (high and low affinity states) in cortical membranes of control mice. GN induced conversion to a one site model (low affinity state). At the time of withdrawal, ISO binding data in cortical membranes were best fit by a one-site model even in the absence of GN. Antagonist binding was not affected. These results resemble those seen after heterologous desensitization, indicating "uncoupling" of receptor and AC. Control cerebellar ISO binding data were similar to cortical data. Chronic ethanol ingestion, however, did not produce data fit by a one site model in cerebellum. The affinity for ISO of the high affinity state of the BAR was significantly decreased at the time of withdrawal. ISO-stimulated AC-activity in cerebellar membranes was not affected by chronic ethanol ingestion, indicating that, in contrast to cerebral cortex, the cerebellar BAR was not uncoupled from AC.
Adv Alcohol Subst Abuse 1988
PMID:Effects of chronic ethanol ingestion on mouse brain beta-adrenergic receptors (BAR) and adenylate cyclase. 285 34

The acute in vitro effects of ethanol on cerebral cortical adenylate cyclase activity and beta-adrenergic receptor characteristics suggested a site of action of ethanol at Gs, the stimulatory guanine nucleotide binding protein. After chronic ethanol ingestion, the beta-adrenergic receptor appeared to be uncoupled (i.e., the form of the receptor with high affinity for agonist was undetectable), and stimulation of adenylate cyclase activity by isoproterenol or guanine nucleotides was reduced, suggesting an alteration in the properties of Gs. To further characterize this change, cholera and pertussis toxin-mediated 32P-ADP-ribosylation of mouse cortical membranes was assessed in mice that had chronically ingested ethanol in a liquid diet. 32P-labeled proteins were separated by SDS-PAGE and quantitated by autoradiography. There was a selective 30-50% decrease in cholera toxin-induced labeling of 46 kDa protein band in membranes of ethanol-fed mice, with no apparent change in pertussis toxin-induced labeling. The 46 kDa protein has a molecular weight similar to that of the alpha subunit of Gs, suggesting a reduced amount of this protein or a change in its characteristics as a substrate for cholera toxin-induced ADP-ribosylation in cortical membranes of ethanol-fed mice.
Adv Alcohol Subst Abuse 1988
PMID:Cholera toxin-induced ADP-ribosylation of a 46 kDa protein is decreased in brains of ethanol-fed mice. 314 19

Abuse of volatile organic solvents among youth remains a major social problem. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a "gateway drug" for users. The effect of repeated inhalation of toluene on subsequent responses to other drugs of abuse is unclear. In the present study, we investigated the effect of toluene inhalation on methamphetamine-induced behavioral change using a newly developed sealed inhalation shuttlebox. The influence of the cyclic AMP response element binding (CREB) protein expression following toluene inhalation was also examined. Mice were exposed to toluene or air once daily for five days. Methamphetamine produced significant hyperlocomotion in air-exposed mice. This stimulatory effect of methamphetamine was significantly enhanced following repeated inhalation of toluene. Furthermore, repeated toluene inhalation increased the levels of CREB proteins in the limbic forebrain. The present study demonstrated that adaptation of the adenylate cyclase system following repeated toluene inhalation might be involved in the expression of behavioral sensitization to subsequent methamphetamine administration. Inhalant abuse could thus be associated with the risk of other substances of abuse.
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PMID:[Neurochemical mechanisms for development of psychological dependence on volatile organic solvents]. 1841 3