Role of Gaq or Gao Proteins in a1-Adrenoceptor Subtype- Mediated Responses in Fischer 344 Rat Aorta

Previous studies showed that a-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 a1band a1d-AR subtypes in 1-month-old rats. We examined the G proteins responsible for a1-AR-mediated contractile response and inositol phosphate accumulation in the aortas of 1-month-old Fischer 344 rats. Pertussis toxin (PTX) treatment (2.5 mg/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 Gaq and Gao but not Gas and Gai precipitated specific a1-AR binding sites labeled with 2-[b(4-hydroxy-3-[I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[b-(4-hydroxy-3-[I]iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by Ga proteins was increased by activating membrane a1-ARs with PHE. Moreover, PHE stimulated the palmitoylation of Gaq and Gao, and this response was blocked by the a1-AR antagonist prazosin. Characterization of the a1-AR subtypes that couple to G proteins indicates that although aortic a1a-, a1b-, and a1d-ARs were associated with Gaq, a1b-AR was also linked to Gao. These results suggest that a1-ARs mediate the contractile response in rat aorta by coupling to both Gq protein and the PTX-sensitive Go protein.