Adenylyl cyclase inhibition and altered G protein subunit expression and ADP-ribosylation patterns in tissues and cells from Gi2α-/- mice

Uwe Rudolph, Karsten Spicher, Lutz Birnbaumer

Research output: Contribution to journalArticle

Abstract

The inhibition of αi2-/- mouse cardiac isoproterenol-stimulated adenylyl cyclase (AC; EC 4.6.1.1) activity by carbachol and that of αi2-/- adipocyte AC by phenylisopropyladenosine (PIA), prostaglandin K:, and nicotinic acid were partially, but not completely, inhibited. While the inhibition of cardiac AC was affected in all αi2-/-animals tested, only 50% of the αi2-/- animals showed an impaired inhibition of adipocyte AC, indicative of a partial penetrance of this phenotype. In agreement with previous results, the data show that Gi2 mediates hormonal inhibition of AC and that Gi3 and/or Gi1, is capable of doing the same but with a lower efficacy. Disruption of the αi2 gene affected about equally the actions of all the receptors studied, indicating that none of them exhibits a striking specificity for one type of Gi over another and that receptors are likely to be selective rather than specific in their interaction with functionally homologous G proteins (e.g., Gi1, Gi2, Gi3). Western analysis of G protein subunit levels in simian virus 40-transformed primary embryonic fibroblasts from αi2+/+ and αi2-/- animals showed that αi2 accounts for about 50% of the immunopositive G protein α subunits and that loss of the αi2 is accompanied by a parallel reduction in Gβ35 and Gβ36 subunits and by a 30-50% increase in αi3. This suggests that Gβγ levels may be regulated passively through differential rates of turnover in their free vs. trimeric states. The existence of compensatory increase(s) in αi, subunit expression raises the possibility that the lack of effect of a missing αi2 on AC inhibition in adipocytes of some αi2-/- animals may be the reflection of a more pronounced compensatory expression of αi3 and/or αi1.

Original languageEnglish (US)
Pages (from-to)3209-3214
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number8
DOIs
StatePublished - Apr 16 1996

Keywords

  • Gene motivation penetrance
  • Pertussis toxin
  • Signal transduction

ASJC Scopus subject areas

  • General

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