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An in vitro analysis of purine‐mediated renal vasoconstriction in rat isolated kidney
Author(s) -
Kenakin Terry P.,
Pike Nicholas B.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb08967.x
Subject(s) - vasoconstriction , vasodilation , adenosine , endocrinology , medicine , purinergic receptor , chemistry , adenosine receptor , pharmacology , biology , receptor , agonist
1 In the rat isolated perfused kidney, 2‐chloroadenosine and l ‐N 6 ‐phenyl‐isopropyl adenosine ( l ‐PIA) produced a modest vasodilatation. 2 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 A 1 ‐purinoceptors mediating adenyl cyclase inhibition and vasodilatation from activation of A 2 ‐purinoceptors stimulating adenyl cyclase. 3 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 A 1 ‐and A 2 ‐purinoceptors. 4 Maximal renal vasoconstriction to 2‐chloroadenosine and l ‐PIA was observed in the presence of 10 m m 8‐SPT; the fact that this vasoconstriction was sensitive to the selective A 1 ‐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 > 2‐chloroadenosine > d ‐PIA > N 6 ‐ethylcarboxamide adenosine (NECA) was consistent with activation of vascular A 1 ‐purinoceptors. 5 While these data are consistent with the hypothesis that purines activate vascular A 1 ‐and A 2 ‐receptors in the rat isolated kidney, the nature of the results did not allow definitive classification of the receptors mediating the purine effects.