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Suramin antagonizes responses to P 2 ‐purinoceptor agonists and purinergic nerve stimulation in the guinea‐pig urinary bladder and taenia coli
Author(s) -
Hoyle Charles H.V.,
Knight Gillian E.,
Burnstock Geoffrey
Publication year - 1990
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.1476-5381.1990.tb12979.x
Subject(s) - suramin , taenia coli , purinergic receptor , carbachol , stimulation , endocrinology , medicine , yohimbine , guinea pig , chemistry , urinary bladder , biology , receptor , adenosine , antagonist
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 μ m ‐1 m m ) caused a non‐competitive antagonism of responses to α,β‐methylene ATP with an estimated pA 2 of approximately 4.7, and inhibited responses to stimulation of the intramural purinergic nerves, with a similar pA 2 value. At a concentration of 10 μ m , suramin had little effect, but at a concentration of 1 μ m , 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 n m ), suramin at 100 μ m and 1 m m significantly antagonized relaxant responses to ATP (at an EC 50 concentration) with an estimated pA 2 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 pA 2 values of 4.9 ± 0.93 and 4.6 ± 1.01, respectively. Suramin had no significant effect at 1 or 10 μ m . 4 Suramin, at any of the concentrations tested, did not affect contractile responses to histamine (10 μ m ) or carbachol (10 μ m ) in the bladder detrusor preparations. In the taenia coli, suramin did not affect either the relaxant responses to noradrenaline (at an EC 50 concentration) or the contractile responses to carbachol (100 n m ). 5 Thus, suramin at concentrations above 10 μ m 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 μ m ) 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 P 2 ‐purinoceptor‐mediated activity rather than that mediated via cholinoceptors, adrenoceptors or histamine receptors.