Characterization and distribution of P2-purinoceptor subtypes in rat pulmonary vessels.
To characterize P2-purinoceptors in pulmonary vessels we have examined the effects of ATP analogs on rat isolated pulmonary artery and vein in vitro. The rank order of potency for causing vasoconstriction was: alpha,beta-methylene-ATP (alpha,beta-meATP) greater than beta,gamma-methylene-ATP (beta,gamma-meATP) greater than 2-methylthio-ATP (2m.S.ATP) greater than ATP for arteries; and alpha,beta-meATP much greater than beta,gamma-meATP = 2m.S.ATP greater than ATP for veins, indicating that a P2x receptor was involved. The contractile response to these analogs was virtually abolished after desensitization of P2x-receptors by alpha,beta-meATP. Removal of the endothelial cells enhanced the contractile responses to all of the ATP analogs in both arteries and veins. The rank order of potency for vasodilatation was 2m.S.ATP much greater than ATP = beta,gamma-meATP much greater than alpha,beta-meATP for arteries and 2m.S.ATP much greater than ATP = beta-gamma-meATP, with alpha,beta-meATP being no effect for veins, indicating a P2y receptor. Pretreatment of the pulmonary arteries with the P2y-antagonist reactive blue 2 caused a rightward shift of the dose-response curves to 2m.S.ATP, ATP and beta,gamma-meATP. Reactive blue 2 was only used with the pulmonary arteries. Removal of the endothelium converted the relaxant responses to all the ATP analogs (except to ATP in pulmonary artery) to further contraction. In the pulmonary artery, the small endothelium-independent relaxation induced by ATP was abolished completely by pretreating the vessels with 100 microM theophylline (a P1-purinoceptor antagonist), suggesting that it was due to conversion of ATP to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
Liu
S F
SF
Department of Thoracic Medicine, National Heart and Lung Institute, London, England.
McCormack
D G
DG
Evans
T W
TW
Barnes
P J
PJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000032:analysis* / Q000187:drug effects; D011667:Pulmonary Veins / Q000032:analysis* / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000032:analysis* / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate