Phentolamine‐induced rhythmic contractions in bladder detrusor muscle of guinea‐pig

1 Phentolamine caused a rhythmic contraction concentration‐dependently without affecting resting tone in the detrusor muscle. 2 Prazosin, yohimbine, propranolol, noradrenaline, Clonidine or isoprenaline failed to cause the rhythmic contraction. These agents did not modify the response to phentolamine suggesting no involvement of α‐or β‐adrenoceptors in the response to phentolamine. 3 Chlorpheniramine, Cimetidine, methysergide, SK&F 83566, atropine, bretylium, hemicholinium or tetrodotoxin failed to inhibit the response to phentolamine. These results suggest that the effect of phentolamine is not mediated through histaminergic, 5‐hydroxytryptaminergic, dopaminergic or cholinergic systems, or through transmitter release from nerve endings. 4 Prostaglandin F2α (PGF2α), arachidonic acid but not ATP caused rhythmic contractions which resembled the response to phentolamine. Potassium also caused a contraction with increasing resting tone. 5 Following treatment with nifedipine, or incubation in a Ca2+‐ free medium, the responses to phentolamine, PGF2α, arachidonic acid and potassium were markedly inhibited or abolished. 6 Cyclo‐oxygenase inhibitors such as indomethacin, aspirin and corticosterone inhibited or abolished the responses to phentolamine and arachidonic acid but did not inhibit the response to PGF2α. 7 The results suggest that the phentolamine‐induced rhythmic contraction may, at least in part, result from the cyclo‐oxygenase metabolite of arachidonic acid in guinea‐pig detrusor muscles and a consequent increase in the transmembrane Ca2+‐influx.