Role of G alpha q or G alpha o proteins in alpha 1-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 micrograms/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-[125I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta-(4-hydroxy-3-[125I]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 Gq protein and the PTX-sensitive G(o) protein.
Gurdal
H
H
Department of Pharmacology, MCP-Hahnemann School of Medicine, Philadelphia, Pennsylvania, USA.
Seasholtz
T M
TM
Wang
H Y
HY
Brown
R D
RD
Johnson
M D
MD
Friedman
E
E
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000648:ultrastructure; D001665:Binding Sites; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010169:Palmitic Acids / Q000378:metabolism; D037342:Pertussis Toxin; D011233:Precipitin Tests; D051381:Rats; D011916:Rats, Inbred F344; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000378:metabolism / Q000502:physiology*; D012680:Sensitivity and Specificity; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D046911:Macromolecular Substances; D010169:Palmitic Acids; D018340:Receptors, Adrenergic, alpha-1; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins