Suramin antagonizes responses to P2‐purinoceptor agonists and purinergic nerve stimulation in the guinea‐pig urinary bladder and taenia coli

Abstract

1 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. 2 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. 3 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. 4 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). 5 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.