Mechanisms of signal transduction for adenosine and ATP in pulmonary vascular bed.
The purpose of the present study was to investigate the contribution of pertussis toxin (PTX)-sensitive guanine nucleotide (G) proteins in the pulmonary vascular response to adenosine and ATP in the intact cat under conditions of controlled pulmonary blood flow and left atrial pressure. Adenosine, ATP, and beta-tau-ATP increased lobar arterial pressure in a dose-dependent manner. The pulmonary vasoconstrictor response to adenosine was abolished by BW 1433U, a specific purinergic receptor (P1) inhibitor, PTX pretreatment, indomethacin, and ONO 3708, a thromboxane A2 (TxA2) receptor antagonist. These data suggest that the pulmonary vasoconstrictor response to adenosine depends on activation of P1 purinergic receptors coupled to PTX-sensitive G proteins and subsequent metabolism of liberated arachidonic acid to form TxA2. Because each blocking agent studied produced similar reductions in the pulmonary vasoconstrictor response to ATP without altering the pulmonary vasoconstrictor response to beta-tau-ATP, the present data suggest that ATP constricts the pulmonary vascular bed, in part, by hydrolysis to adenosine. Moreover, the present study suggests that both A1 purinoceptors that are linked to PTX-sensitive G proteins as well as P2x purinoceptors receptors that are independent of PTX-insensitive G proteins mediate the pulmonary vasoconstrictor response to ATP in vivo.
Department of Internal Medicine, Louisiana State University Medical School, New Orleans.
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002415:Cats; D015237:Dinoprost / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology; D037342:Pertussis Toxin; D015230:Prostaglandin D2 / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D011810:Quinoxalines; D010566:Virulence Factors, Bordetella; D014970:Xanthines; D000068438:Brimonidine Tartrate; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C049855:ONO 3708; D000255:Adenosine Triphosphate; C053414:BW A1433U; D015237:Dinoprost; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D008729:Methoxamine; D000241:Adenosine; D015230:Prostaglandin D2; D007213:Indomethacin