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Vol. 52, Issue 6, 1064-1070, 1997

Role of Galpha q or Galpha o Proteins in alpha 1-Adrenoceptor Subtype-Mediated Responses in Fischer 344 Rat Aorta

Hakan Gurdal, Tammy M. Seasholtz, Hoau-Yan Wang, R. Dale Brown, Mark D. Johnson, and Eitan Friedman

Department of Pharmacology, MCP-Hahnemann School of Medicine, Philadelphia, Pennsylvania (H.G., T.S., H.Y.W., M.D.J., E.F.), Department of Pharmacology, the Medical School of Ankara University Ankara, Turkey (H.G.), and Research and Development Service, Edward Hines Jr. Veterans' Administration Hospital, Hines, Illinois (R.D.B.)

Previous studies showed that alpha -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 alpha 1b- and alpha 1d-AR subtypes in 1-month-old rats. We examined the G proteins responsible for alpha 1-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 Galpha q and Galpha o but not Galpha s and Galpha i precipitated specific alpha 1-AR binding sites labeled with 2-[beta -(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta -(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by Galpha proteins was increased by activating membrane alpha 1-ARs with PHE. Moreover, PHE stimulated the palmitoylation of Galpha q and Galpha o, and this response was blocked by the alpha 1-AR antagonist prazosin. Characterization of the alpha 1-AR subtypes that couple to G proteins indicates that although aortic alpha 1a-, alpha 1b-, and alpha 1d-ARs were associated with Galpha q, alpha 1b-AR was also linked to Galpha o. These results suggest that alpha 1-ARs mediate the contractile response in rat aorta by coupling to both Gq protein and the PTX-sensitive Go protein.

Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics