A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle

Abstract

We investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1–50Hz for 5s at 1min intervals, 0.1ms pulse width, 60V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10μM). Tetrodotoxin (TTX: 1μM) inhibited contractile 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 unaffected by omega-conotoxin GVIA (ω-CTX: 0.1μM). The atropine-resistant contractions were unaffected by the P₂-purinoceptor antagonists suramin (300μM) and PPADS (30μM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10μM–1mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300μM) and PPADS (3, 10, 30μM) was insurmountable, with apparent ‘pA₂’ values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P₂-purinoceptors on the effector cells. The TTX- and ω-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na⁺- and N-type Ca²⁺-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984).