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Identification of ethanol responsive domains of adenylyl cyclase.

Identification of ethanol responsive domains of adenylyl cyclase. Research Abstract Details 

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  • Identification of ethanol responsive domains of adenylyl cyclase. Abstract Text:

    masami yoshimuraMasami Yoshimura,susan pearsonSusan Pearson,yoichi kadotaYoichi Kadota,cristina e gonzalezCristina E Gonzalez,

    BACKGROUND: The activity of adenylyl cyclase (AC) is enhanced by pharmacologically relevant concentrations of ethanol. The enhancing effect of ethanol on AC activity is AC isoform-specific. Therefore, we hypothesized that within a cyclic AMP-generating system, AC is the target of ethanol's action and that ethanol-sensitive AC molecules contain structural elements modulated by ethanol. The structural elements are designated as "ethanol responsive domains." METHODS: By using a series of chimeric mutants, we searched regions of the AC molecule that are important for the ethanol effect. These chimeric mutants were derived from 3 isoforms of AC: AC7 (type 7), the most ethanol responsive isoform; AC3 (type 3), an isoform that is far less responsive to ethanol; and AC2 (type 2), an isoform that is homologous to AC7 but less responsive to ethanol. RESULTS: We identified 2 discrete regions of the AC molecule that are important for the enhancement of AC activity by ethanol. The first is the N-terminal 28-amino-acid (aa) region of the C(1a) domain. The second is the C-terminal region ( approximately 140 aa) of the AC molecule. Sequence differences in the N-terminal tail, 2 putative transmembrane domains, and the C(1b) domain are not important for ethanol's effect. CONCLUSIONS: The current study with mammalian ACs provides a new class of alcohol-responsive protein and possibly a new mechanism of alcohol action on cellular function. The identification of ethanol responsive domains will facilitate the elucidation of the mechanisms by which ethanol enhances the activity of AC.

    Identification of ethanol responsive domains of adenylyl cyclase. Publishing Authors By Initials

    m yoshimuraM Yoshimura,s pearsonS Pearson,y kadotaY Kadota,ce gonzalezCE Gonzalez,

    For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

    PUBMED ID PMID:

    MEDLINE DATE:

    Identification of ethanol responsive domains of adenylyl cyclase. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Alcoholism, clinical and experimental research

    VOLUME: 30

    Page Numbers: 1824-32

    Journal Abbreviation: Alcohol. Clin. Exp. Res.

    ISSN: 0145-6008

    DAY: 3

    MONTH: Nov

    YEAR: 2006

    Identification of ethanol responsive domains of adenylyl cyclase. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7707242

    Identification of ethanol responsive domains of adenylyl cyclase. Keywords Mesh Terms:

    KEYWORDS: Transfection

    MESH TERMS: drug effects

    Chemical & Substance for Abstract: Identification of ethanol responsive domains of adenylyl cyclase. Information

    Substance Name: Adenylate Cyclase

    Registry Number: EC 4.6.1.1

    Grant and Affiliation Information for Identification of ethanol responsive domains of adenylyl cyclase.

    AFFILIATION: Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO, USA. myoshimura@vetmed.lsu.edu

    Country: England

    England Research PublicationEngland Research Publication

    AGENCY: United States NIAAA

    GRANT: AA 13148

    ACRONYM: AA

    MEDLINETA: Alcohol Clin Exp Res

    REFSOURCE:

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    ACCESSION NUMBER:

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