Suramin: a selective inhibitor of purinergic neurotransmission in the rat isolated vas deferens.
The effects of the putative P2 purinoceptor antagonist suramin on contractile responses of the rat isolated vas deferens to electrical field stimulation and exogenously applied drugs (alpha,beta-methylene ATP and noradrenaline) were investigated. Suramin was devoid of agonist activity in the rat vas deferens. The response of the vas deferens to single pulse field stimulation was characteristically biphasic with a large first component peaking between 260-300 ms after the stimulus followed by a second smaller component peaking at about 650 ms post-stimulus. Suramin (100 nM-1 mM) selectively impaired the first, purinergic phase of the response to single pulse field stimulation but was without effect on the second, noradrenergic component. The response of the vas deferens to trains of electrical field stimuli (10 Hz for 10 s) was also biphasic. Suramin (1 microM-1 mM) reduced the first (less than 1 s) phase of the response by 30%, the second (greater than 5 s) plateau phase by 50% and inhibited the intermediate (2-4 s) phase by 80%. Dose-contact periods of 20 or 30 min respectively were sufficient to achieve equilibration of the inhibitory effects of suramin against the responses to single pulse field stimulation or trains of pulses. Following 30 min incubation with 1 mM suramin, the remaining first and second phase components of the response to trains of pulses were impaired and subsequently abolished by the alpha 1-adrenoceptor antagonist WB4101 establishing their noradrenergic origin. Suramin (300 microM) abolished responses of the vas deferens to alpha,beta-methylene ATP but was without effect on those to noradrenaline. Suramin (30 microM) induced a rightward shift in the concentration-response relationship to alpha,beta-methylene ATP that was associated with a significant 40% increase in the maximum response, but did not modify responses to noradrenaline. The inhibitory effects of suramin (3-300 microM) on responses of the vas deferens to approximate EC50 concentrations of alpha,beta-methylene ATP were reversible on repeated washout for 40-60 min. These results reveal suramin to be a useful pharmacological tool for the study of purinergic neurotransmission in rodent vasa deferentia.
Mallard
N
N
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, South Glamorgan, UK.
Marshall
R
R
Sithers
A
A
Spriggs
B
B
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D058914:Purinergic Antagonists; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation
D058914:Purinergic Antagonists; D013498:Suramin; D000255:Adenosine Triphosphate; D009543:Nifedipine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine