SURAMIN ANTAGONIZES RESPONSES TO P2-PURINOCEPTOR AGONISTS AND PURINERGIC NERVE-STIMULATION IN THE GUINEA-PIG URINARY-BLADDER AND TAENIA-COLI

Suramin, an inhibitor of several types of ATPase, was investigated for its ability to antagonize responses mediated via P(2X)-purinoceptors in the guinea-pig urinary bladder and P(2Y)-purinoceptors in the guinea-pig taenia coli. In isolated strips of bladder detrusor muscle, suramin (100 μM-1 mM) caused a non-competitive antagonism of responses to α,β-methylene ATP with an estimated pA2 of approximately 4.7, and inhibited responses to stimulation of the intramural purinergic nerves, with a similar pA2 value. At a concentration of 10 μM, suramin had little effect, but at a concentration of 1 μM, suramin potentiated responses to α,β-methylene ATP, and potentiated responses to electrical stimulation of intramural purinergic nerves. In isolated strips of taenia coli, in which a standard tone had been induced by carbachol (100 nM), suramin at 100 μM and 1 mM significantly antagonized relaxant responses to ATP (at an EC50 concentration) with an estimated pA2 of 5.0 ± 0.82 and relaxant responses to electrical stimulation of the intramural non-adrenergic, non-cholinergic inhibitory nerves, either single pulses or trains of 8 Hz for 10 s, with estimated pA2 values of 4.9 ± 0.93 and 4.6 ± 1.01, respectively. Suramin had no significant effect at 1 or 10 μM. Suramin, at any of the concentrations tested, did not affect contractile responses to histamine (10 μM) or carbachol (10 μM) in the bladder detrusor preparations. In the taenia coli, suramin did not affect either the relaxant responses to noradrenaline (at an EC50 concentration) or the contractile responses to carbachol (100 nM). Thus, suramin at concentrations above 10 μM blocked actions mediated via P(2X)- and P(2Y)-purinoceptors in the guinea-pig urinary bladder and taenia coli respectively. Potentiation of purinoceptor-mediated activity was seen only at a low concentration of suramin (1 μM) and only in the urinary bladder (P(2X)-purinoceptor). For its antagonistic activity suramin did not discriminate between P(2X)- and P(2Y)-purinoceptors, but it was selective for P2-purinoceptor-mediated activity rather than that mediated via cholinoceptors, adrenoceptors or histamine receptors.