Presynaptic effects of scopolamine, oxotremorine, noradrenaline and morphine on [3H] acetylcholine release from the myenteric plexus at different stimulation frequencies and calcium concentrations

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Abstract
Summary The inhibition by three modulators (oxotremorine, noradrenaline, morphine) of acetylcholine release from the myenteric plexus preincubated with [3H]choline was investigated at different stimulation frequencies and calcium concentrations. Moreover, [3H]acetylcholine release evoked by a low (0.1 Hz) or a high (10 Hz) stimulation rate was investigated at different calcium concentrations either in the absence or presence of scopolamine. A reduced calcium concentration (0.6 mmol/l) inhibited acetylcholine release more at 0.1 Hz (74% ± 3%) than at 10 Hz (44% ± 8%). Scopolamine enhanced the stimulated acetylcholine release at a calcium concentration of 1.8 mmol/l. At calcium concentrations higher than 1.8 mmol/l scopolamine failed to enhance transmitter release markedly. A reduction of the calcium concentration (< 1.8 mmol/l) significantly enhanced the effect of scopolamine, when acetylcholine release was evoked at 0.1 Hz. Oxotremorine (10 μmol/l) completely suppressed acetylcholine release at 1 Hz (120 pulses). When 120 pulses were applied at 10 Hz the maximal effect was only a 64% inhibition and the concentration-response curve was significantly shifted to the right. However, after a reduction of both the train length or the calcium concentration oxotremorine produced a complete inhibition of acetylcholine release evoked at 10 Hz. In contrast to the effect of oxotremorine, the concentration-response curves for morphine and noradrenaline were similar at 1 Hz and 10 Hz. Following conclusions can be drawn: 1. The present findings fit into the concept that residual calcium accumulates in the nerve terminal during 10 Hz stimulation. 2. The results obtained with scopolamine and oxotremorine are consistent with the view that muscarine autoreceptor activation triggers a reduction of the intraneuronal availability of calcium for the stimulus-secretion coupling. 3. The presynaptic effect of morphine and partly that of noradrenaline might be mediated by a different mechanism, probably by a reduction of release sites.