A REAPPRAISAL OF THE NATURE OF THE ATROPINE-RESISTANT CONTRACTION TO ELECTRICAL-FIELD STIMULATION IN THE HUMAN ISOLATED DETRUSOR MUSCLE

We investigated whether in human isolated detrusor strips the atropine -resistant contractile response to electrical field stimulation was me diated by ATP (or a related purine), as previously shown in the urinar y bladder of other mammalian species. Electrical stimulation (1-50 Hz for 5 s at 1 min intervals, 0.1 ms pulse width, 60 V) elicited reprodu cible, frequency-dependent twitch contractions, which were markedly re duced by atropine (10 mu M). Tetrodotoxin (TTX: 1 mu M) inhibited cont ractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaf fected by omega-conotoxin GVIA (omega-CTX: 0.1 mu M). The atropine-res istant contractions were unaffected by the P-2-purinoceptor antagonist s suramin (300 mu M) and PPADS (30 mu M), at concentrations which virt ually suppressed the contractile response induced by applied ATP (10 m u M-1 mM). As previously described, antagonism of the ATP-induced cont ractions by suramin (30, 100, 300 mu M) and PPADS (3, 10, 30 mu M) was insurmountable, with apparent 'pA(2)' values (calculated at the lowes t antagonist concentrations) of 4.9 and 5.2, respectively, It is concl uded that, under our experimental conditions, the non-cholinergic (atr opine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite or the pr esence of excitatory P-2-purinoceptors on the effector cells. The TTX- and omega-CTX-resistant, non-cholinergic component might be related t o the release of unknown transmitter(s) through a mechanism independen t of both Na+- and N-type Ca2+-channels. More likely, the atropine-res istant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984).