The inhibitory action of tamoxifen on the contraction of Ascaris suum somatic muscle in response to acetylcholine

The somatic muscle of Ascaris suum is principally under the excitatory cont rol of neuromuscular junction transmitter, acetylcholine (ACh). However, it has recently been shown that neuropeptides also play an important role in the motor-nervous system and one of these, AF3 (AVPGVLRFamide), also contra cts muscle. The events which trigger contraction to ACh and AF3 would appea r to be different, with ACh activating a nicotinic acetylcholine receptor w hilst the response to AF3 is most likely to involve a C-protein coupled rec eptor negatively coupled to adenylate cyclase. In order to further elucidat e differences in the cellular signalling pathways through which ACh and AF3 elicit muscle contraction, we investigated the actions of protein kinase C inhibitors, tamoxifen and chelerythrine, on the dorsal somatic muscle stri p of A. suum. Contractions in response to 1 mu M AF3 were potentiated by 17 % in the presence of 10 mu M tamoxifen (P < 0.05; n = 8); however, contract ions in response to 10 mu M ACh were markedly inhibited (tamoxifen IC50 44 +/- 18 mu M; n = 6). Tamoxifen also blocked muscle cell depolarizations to 5 mu M ACh (IC50 4 +/- 1 mu M; n = 6) and 1 mu M levamisole (IC50 14 +/- 6 mu M; n = 4). This was unlikely to be a non-specific effect on the membrane as hyperpolarizations to 10 mu M GABA were unaffected (93% of control with 10 mu M tamoxifen; n = 6; P > 0.05). However, another inhibitor of mammali an protein kinase C, chelerythrine, did not affect the response either to A Ch or AF3 (n = 6).