An in vitro analysis of purine-mediated renal vasoconstriction in rat isolated kidney.
In the rat isolated perfused kidney, 2-chloroadenosine and L-N6-phenyl-isopropyl adenosine (L-PIA) produced a modest vasodilatation. After kidneys had been pretreated with methoxamine (to elevate vascular tone) and forskolin (to activate adenyl cyclase and reduce vascular tone), both purine agonists produced vasoconstriction at low doses and vasodilatation at higher doses. This was consistent with the working hypothesis that vasoconstriction resulted from activation of A1-purinoceptors mediating adenyl cyclase inhibition and vasodilatation from activation of A2-purinoceptors stimulating adenyl cyclase. These kidney preparations also demonstrated a marked potentiation of purine-mediated vasoconstriction in the presence of various concentrations of 8-p-sulpho-phenyltheophylline (8-SPT), a drug reported in the literature to be a competitive antagonist of A1- and A2-purinoceptors. Maximal renal vasoconstriction to 2-chloroadenosine and L-PIA was observed in the presence of 10 mM 8-SPT; the fact that this vasoconstriction was sensitive to the selective A1-receptor antagonist 8-(2-amino-4-chlorophenyl)-1,3-dipropylxanthine (PACPX) and that the order of potency of agonists for this effect was L-PIA greater than 2-chloroadenosine greater than D-PIA greater than N6-ethylcarboxamide adenosine (NECA) was consistent with activation of vascular A1-purinoceptors. While these data are consistent with the hypothesis that purines activate vascular A1- and A2-receptors in the rat isolated kidney, the nature of the results did not allow definitive classification of the receptors mediating the purine effects.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
D011983:Receptors, Purinergic; D014970:Xanthines; D015762:2-Chloroadenosine; D005576:Colforsin; D010660:Phenylisopropyladenosine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D008729:Methoxamine; D000241:Adenosine