Characterization of 5-HT receptors in the parasitic nematode, Ascaris suum

The pharmacological profiles of the 5-hydroxytryptamine (5-HT) receptors on Ascaris suum pharyngeal and somatic body wall muscles were investigated. T he mechanisms involved following activation of these receptors were also st udied. 5-HT activated and maintained pumping in isolated pharynxes with an EC-50 value of 44 +/- 1.7 muM. The 5-HT agonists, tryptamine, sumatriptan 8 -OH-DPAT and 5-carboxyamidotryptamine all failed to stimulate pumping. The 5-HT2 antagonist, ketanserin, initially excited and then inhibited pumping while the 5-HT4 antagonist, ondansetrun, had no effect. 5-HT and 5-HT agoni sts, 8-OH-DPAT, 5-carboxyamidotryptamine, alpha -methyl-5-HT and tryptamine all inhibited ACh-induced contractions of a somatic body wall muscle strip . Ketanserin partially blocked the inhibitory effect of alpha -methyl-5-HT and ACh-induced contractions while the 5-HT uptake blocker, fluoxetine, pot entiated the effect of 5-HT on ACh-induced contractions. Basal levels of cA MP, 1540 +/- 232 pmol/mg, in pharyngeal muscle and 1721 +/- 134 pmol/ mg, s omatic body wall muscle, were both increased by forskolin. 5-HT had no effe ct on pharyngeal muscle cAMP levels but raised cAMP levels in somatic body wall muscle, e.g. 100 muM 5-HT, raised the level to 2851 +/- 212 pmol/mg an d 1000 muM raised levels to 4578 +/- 1234 pmol/mg. 5-HT, 1000 muM, increase d inositol phosphate levels in pharyngeal muscle. These results provide som e evidence for a 5-HT2-like receptor on pharyngeal muscle. In contrast, the situation on somatic body wall muscle is more confusing since the pharmaco logical profile partly indicates a 5-HT2-like receptor but this receptor is linked to a rise in cAMP levels. Further studies are required to resolve t he position but they. must be based on the rational design of ligands speci fically for nematode 5-HT receptors and not simply using ligands developed for the classification of mammalian 5-HT receptors. Such a design must take into account data from molecular biology studies of nematode 5-HT receptor s.