Role of Gαq or Gαo proteins in α1-adrenoceptor subtype mediated responses in Fischer 344 rat aorta

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 mu g/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 G(alpha q) and G(alpha o) but not G(alpha s) and G(alpha i) precipitated specific alpha(1)-AR binding sites labeled with 2-[beta-(4-hydroxy-3-[I-125]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta-(4-hydroxy-3-[I-125] iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by G(alpha) proteins was increased by activating membrane alpha(1)-ARs with PHE. Moreover, PHE stimulated the palmitoylation of G(alpha q) and G(alpha 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 G(alpha q), alpha(1b)-AR was also linked to G(alpha o). These results suggest that alpha(1)-ARs mediate the contractile response in rat aorta by coupling to both G(q) protein and the PTX-sensitive G(o) protein.