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
- Received March 31, 1997.
- Accepted September 9, 1997.
-
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.
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|