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)

The binding of agonists and antagonists to beta-adrenergic receptors in brain tissue obtained postmortem in nonalcoholic controls and matched intoxicated and sober alcoholics was measured to assess the state of the receptors and their coupling to adenylate cyclase. Binding of antagonist, iodocyanopindolol, to cerebral cortical and cerebellar membrane preparations was not different in alcoholics compared to that in controls, suggesting that the number of beta-adrenergic receptors was not affected by chronic ethanol ingestion. Agonist binding data, however, indicated the loss of the high-affinity agonist binding state of the beta-adrenergic receptor, representing the receptor-guanine nucleotide binding protein (Gs) complex. Such changes were observed in cerebral cortex but not in cerebellum of intoxicated alcoholics. These data suggest that cerebral cortical beta-adrenergic receptors are uncoupled from adenylate cyclase in these subjects. In cerebral cortical and cerebellar membranes of sober alcoholics both the high- and low-affinity agonist binding sites were observed. These findings are similar to those seen in animal studies and suggest that the effect of chronic ethanol ingestion on beta-adrenergic receptor-adenylate cyclase coupling is brain region specific and reversible with abstinence. Ethanol-induced changes in the coupling of receptors to adenylate cyclase may contribute to the physiological and behavioral manifestations of alcohol abuse.
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PMID:Beta-adrenergic receptor binding in brain of alcoholics. 254 90

Multiple symmetric lipomatosis (MSL) (or Madelung's disease or Launois-Bensaude syndrome) is a rare inherited disease clinically characterized by a massive development of large symmetric unencapsulated lipomas on the subcutaneous tissue of face, neck, trunk and arms, resulting in a grotesque aspect of the patient. Less frequently the accumulation of excessive fatty tissue can spread deeply to the superficial fascia. Peripheral neuropathy, macrocytic anemia and chronic hepatopathy have been reported to cohesist. Macrocytic anaemia and chronic hepatopathy are probably secondary to high alcohol consumption, that is frequently associated. MSL, that was first described by Sir Benjamin Brodie in 1846, affects mainly the men (ratio man/woman 30:1), with an incidence in Mediterranean area of 1:25.000 men; the ages at onset range from 20 to 50 years. It is not known yet the pathway of inheritance and the molecular basis of the genetic defect responsible for the development of fat accumulation. It has been postulated a defective lipolytic response to catecholamines; this altered response could be due to an abnormal amount or a defective function of Gs-protein, the coupler between beta-adrenergic receptors on the surface of adipocytes and adenylate cyclase, or, alternatively, the defect could be in the catalytic unit of adenylate cyclase. The number and function of alpha- and beta-adrenergic receptors and the lipolytic response to cAMP (the second messenger) are normal. Recently it has been hypothesized that the defective lipolysis is due to a disorder in the mitochondria of brown fat, whose distribution is similar to the peculiar position of the lipomas in this pathology; the brown fat, unlike white adipose tissue, has abundant mitochondria. The alcohol abuse, frequently present in these subjects, might facilitate the clinical expression of the molecular defect. The therapy of lipomas is essentially surgical, but this approach is not easy, because the lipomas are not capsulated and extremely vascularized. Moreover the surgical excision is not always a successful treatment for the lipomas as they frequently recurrent after a short period from the exeresis. In this report we describe a 59-years old white man, alcohol abuser, with a typical clinical picture of MSL, developed when he was 37 years old. The patient presented multiple lipomas around the shoulders, face, neck and arms, that had been surgically excised eight times. Magnetic resonance imaging showed the presence of fat deposits also in the mediastinum, that caused a tracheal compression. Hepatic cirrhosis and serious side effects from peripheral neuropathy, represented by Charcot's joint and neuropathic ulcer on the sole foot were observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Symmetric multiple lipomatosis with Charcot's joint and neuropathic ulcer. Description of a clinical case]. 838 91

In this paper, we review the current status of genetic markers for the development of alcohol abuse. Family, twin, half-sibling and adoption studies of alcoholic subjects suggest that the heritability of liability to alcoholism is at least 50%. These findings have fuelled intensive investigation in the fields of neurology, biochemistry, genetics and molecular biology aimed at the identification of markers for the risk of alcoholism. The most promising of these are discussed in detail. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) polymorphisms, specifically the ADH3*1, ADH2*2, and ALDH2*2 genotypes appear to confer a protective effect against alcoholism, most notably in Oriental subjects. Caucasian alcohol abusers and their first-degree relatives exhibit depressed platelet monoamine oxidase activity, the degree of which is greater in Type II than Type I alcoholics. Electrophysiological characteristics of alcoholics and those at risk for developing alcoholism have also been identified, including the reduced amplitude of the event-related brain potential and, after ethanol ingestion, characteristic EEG alpha-wave activity. Lower platelet adenylate cyclase activity is seen in alcoholics compared to controls, presumably as a result of over-expression of an inhibitory G-protein. Markers related to other signal transduction pathways of the central nervous system including the serotoninergic, muscarinic and dopaminergic systems are also discussed. In this group of markers, the putative association between the inheritance of the AI allele of the D2 dopamine receptor and the susceptibility to alcoholism provides the most dramatic illustration of the challenges presently existing in this field of scientific investigation. Current limitations in the definition, diagnosis and classification of alcoholism, the confounding influences of race and gender on association studies, as well as the statistical approach of linkage studies are discussed as they relate to the endeavor to uncover valid genetic markers for the risk of alcoholism.
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PMID:Genetic markers of alcohol abuse. 911 63

Given the spectacular advances of genetics during the last five years, it seems appropriate to revisit the important subject of genetics of alcoholism and substance abuse. In recent studies alcohol abuse was shown to have an hereditability of roughly 38%, whereas psychostimulant and opiate use exhibit hereditabilities of 11 to 45%. The hereditability of smoking was found to be around 50%. There is a strong comorbidity between alcoholism and smoking. More than 80% of alcoholics smoke cigarettes in the U.S.A. Other genetic methods such as linkage analysis, allele sharing methods, association studies and analysis of inbred, transgenic and gene-knockout rodents, have partially agreed in showing that the 5HT-1B serotonin receptor and the DRD1, DRD2 and DRD4 dopamine receptors, as well as the dopamine transporter DAT, play an important role in behaviors related to alcoholism and substance abuse. Some neurochemical markers, as for example monoamine oxidase and adenylate cyclase have also been implicated in addictive disorders. The aldehyde dehydrogenase allele ALDH2*2 has a protective effect against alcoholism. Two whole genome linkage studies have shown linkage to chromosomal regions that are in the proximity of the DRD4 dopamine receptor, the GABA receptor gene cluster and the alcohol dehydrogenase gene cluster.
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PMID:[Genetics of addictive disorders]. 1134 17

A light-regulated adenylyl cyclase, mPAC, was previously identified from the cyanobacterium Microcoleus chthonoplastes PCC7420. MPAC consists of a flavin-based blue light-sensing LOV domain and a catalytic domain. In this work, we expressed mPAC in an adenylate cyclase A null mutant (aca-) of the eukaryote Dictyostelium discoideum and tested to what extent light activation of mPAC could restore the cAMP-dependent developmental programme of this organism. Amoebas of Dictyostelium, a well-established model organism, generate and respond to cAMP pulses, which cause them to aggregate and construct fruiting bodies. mPAC was expressed under control of a constitutive actin-15 promoter in D. discoideum and displayed low basal adenylyl cyclase activity in darkness that was about five-fold stimulated by blue light. mPAC expression in aca- cells marginally restored aggregation and fruiting body formation in darkness. However, more and larger fruiting bodies were formed when mPAC expressing cells were incubated in light. Extending former applications of light-regulated AC, these results demonstrate that mPAC can be used to manipulate multicellular development in eukaryotes in a light dependent manner.
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PMID:A cyanobacterial light activated adenylyl cyclase partially restores development of a Dictyostelium discoideum, adenylyl cyclase a null mutant. 2512 13