Abstract
In guinea pig main pulmonary artery precontracted with noradrenaline, adenosine exerted an initial phasic contraction followed by a tonic contraction and a slow relaxation. After selective blockade by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX: 10 nM) of A1 receptors, adenosine only elicited a rapid relaxation. This initial response was characterized by use of adenosine (AR) and its analogues N6-cyclopentyl-adenosine (CPA), R-N6-phenylisopropyladenosine (R-PIA), 2-chloroadenosine (CADO), 5'-N-ethyl-carboxamidoadenosine(NECA), N6-2-(4-aminophenyl) ethyl adenosine (APNEA) and 2-p-((carboxyethyl)-phenethylamino)-5'-carboxamidoadenosine (CGS 21 680). The order of potency of the adenosine analogues for purine-induced phasic contraction was CPA > R-PIA > NECA = APNEA > AR > CGS 21 680 suggesting the involvement of activation of A1 type adenosine receptors in the contraction phase. DPCPX antagonized the CPA-induced contraction with a pA2 = 9.27 +/- 0.26, but the Schild plot slope parameter was significantly lower than unity (0.58 +/- 0.09). In contrast, in electrically driven guinea pig atrial myocardium (a tissue reported to possess A1 receptors), the DPCPX-CPA antagonism was purely competitive (pA2 = 8.95 +/- 0.06; slope = 0.93 +/- 0.06). In the presence of 300 nM DPCPX, the rank order of potency for the purine-induced fast relaxation was NECA > CADO = AR > CGS 21 680 = R-PIA > CPA. The NECA- and adenosine-induced relaxation was influenced neither by 300 nM CP 66713 (an antagonist at A2a receptors), nor by endothelial removal and inhibition of nitric oxide synthase (100 microM NG-nitro-L-arginine: L-NOARG).(ABSTRACT TRUNCATED AT 250 WORDS)
Published Version
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