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

Published online by Cambridge University Press:  16 October 2009

N. TRIM
Affiliation:
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
L. HOLDEN-DYE
Affiliation:
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
R. J. WALKER
Affiliation:
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK

Abstract

The somatic muscle of Ascaris suum is principally under the excitatory control 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 contracts muscle. The events which trigger contraction to ACh and AF3 would appear to be different, with ACh activating a nicotinic acetylcholine receptor whilst the response to AF3 is most likely to involve a G-protein coupled receptor negatively coupled to adenylate cyclase. In order to further elucidate 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 strip of A. suum. Contractions in response to 1 μM AF3 were potentiated by 17% in the presence of 10 μM tamoxifen (P<0·05; n=8); however, contractions in response to 10 μM ACh were markedly inhibited (tamoxifen IC50 44±18 μM; n=6). Tamoxifen also blocked muscle cell depolarizations to 5 μM ACh (IC50 4±1 μM; n=6) and 1 μM levamisole (IC50 14±6 μM; n=4). This was unlikely to be a non-specific effect on the membrane as hyperpolarizations to 10 μM GABA were unaffected (93% of control with 10 μM tamoxifen; n=6; P>0·05). However, another inhibitor of mammalian protein kinase C, chelerythrine, did not affect the response either to ACh or AF3 (n=6).

Type
Research Article
Copyright
© 1999 Cambridge University Press

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