Role of Gαq or Gαo Proteins in α1-Adrenoceptor Subtype-Mediated Responses in Fischer 344 Rat Aorta

  1. Hakan Gurdal1,2,
  2. Tammy M. Seasholtz1,
  3. Hoau-Yan Wang1,
  4. R. Dale Brown3,
  5. Mark D. Johnson1 and
  6. Eitan Friedman1
  1. 1Department of Pharmacology, MCP-Hahnemann School of Medicine, Philadelphia, Pennsylvania (H.G., T.S., H.Y.W., M.D.J., E.F.),2Department of Pharmacology, the Medical School of Ankara University Ankara, Turkey (H.G.), and 3Research and Development Service, Edward Hines Jr. Veterans’ Administration Hospital, Hines, Illinois (R.D.B.)

    Abstract

    Previous studies showed that α-adrenoceptor (AR) stimulation with norepinephrine is more potent at eliciting contraction in aortas from 1-month-old Fischer 344 rats than from older rats and that this response is mediated by α1b- and α1d-AR subtypes in 1-month-old rats. We examined the G proteins responsible for α1-AR-mediated contractile response and inositol phosphate accumulation in the aortas of 1-month-old Fischer 344 rats. Pertussis toxin (PTX) treatment (2.5 μg/ml for 4 hr) of aortic rings partially inhibited phenylephrine (PHE)-stimulated contraction and inositol phosphate accumulation, suggesting the involvement of PTX-sensitive and -insensitive G proteins. Specific antisera directed against Gαq and Gαo but not Gαs and Gαi precipitated specific α1-AR binding sites labeled with 2-[β-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[β-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by Gα proteins was increased by activating membrane α1-ARs with PHE. Moreover, PHE stimulated the palmitoylation of Gαq and Gαo, and this response was blocked by the α1-AR antagonist prazosin. Characterization of the α1-AR subtypes that couple to G proteins indicates that although aortic α1a-, α1b-, and α1d-ARs were associated with Gαq, α1b-AR was also linked to Gαo. These results suggest that α1-ARs mediate the contractile response in rat aorta by coupling to both Gq protein and the PTX-sensitive Go protein.

    Footnotes

    • Send reprint requests to: Eitan Friedman, Ph.D., Division of Molecular Pharmacology, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, 3200 Henry Avenue, Philadelphia, PA 19129. E-mail: friedmane{at}auhs.edu

    • This work was supported by the American Heart Association, Southeastern Pennsylvania and Delaware Affiliates; United States Public Health Service Grants AG07700, AG14510, and AG13282 (Nathan Shock Center of Excellence); Allegheny Health Education and Research Foundation; and Turkish Scientific Council Grant TUBITAK-SBAG 1634.

    • Abbreviations:
      AR
      adrenoceptor
      PHE
      phenylephrine
      NE
      norepinephrine
      IP
      inositol phosphate
      PTX
      pertussis toxin
      PLC
      phospholipase C
      [125I]HEAT
      2-[β-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone
      PSS
      physiological salt solution
      PBS
      phosphate-buffered saline
      TBS
      Tween-20 containing phosphate-buffered saline
      SDS
      sodium dodecyl sulfate
      ECL
      enhanced chemiluminescence
      HEPES
      4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
      ANOVA
      analysis of variance
      • Received March 31, 1997.
      • Accepted September 9, 1997.
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    1. Molecular Pharmacology December 1, 1997 vol. 52 no. 6 1064-1070
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