The purinoceptors of the guinea-pig isolated taenia caeci

Abstract

The guinea-pig taenia caeci contains both P 1 and P 2 purinoceptors mediating relaxation. The P 2 purinoceptors have been further characterized using an experimental approach designed to minimise complicating factors. In the presence of the adenosine uptake inhibitor S-(4-nitrobenzyl)-6-thioinosine (NBTI, 300 nM) and a pA 100 concentration of the P 1 purinoceptor antagonist 8-sulphophenyltheophylline (140 μM), the potency order of agonists was: 2-methylthio-ATP ⪢ adenosine 5′-triphosphate (ATP) = α,β-methylene ATP > β,γ-methylene ATP ⪢ uridine 5′-triphosphate. Suramin antagonized ATP (pA 2 = 5.52 ± 0.17, Schild plot slope = 0.67 ± 0.08) and 2-methylthio-ATP (pA 2 = 5.78 ± 0.30, Schild plot slope = 1.37 ± 0.39) while responses to 5′- N-ethylcarboxamidoadenosine (NECA) were unaffected. The findings suggest that suramin, while it is selective for P 2 relative to P 1 purinoceptors, is not a true competitive antagonist. Pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) antagonized ATP in isolated guinea-pig vas deferens, but had no effect on responses to ATP in guinea-pig taenia caeci indicating it is selective for P 2X relative to P 2Y purinoceptors.