title: Identification of ethanol responsive domains of adenylyl cyclase.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO, USA. myoshimura@vetmed.lsu.edu
authors.forename: Masami
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Susan
authors.initials: S
authors.lastname: Pearson
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kadota
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Gonzalez
mesh_terms: D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050506:Mutant Chimeric Proteins / Q000235:genetics; D009154:Mutation; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D002492:Central Nervous System Depressants; D018076:DNA, Complementary; D007527:Isoenzymes; D050506:Mutant Chimeric Proteins; D000431:Ethanol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases