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

Abstract

The pharmacological profiles of the 5-hydroxytryptamine (5-HT) receptors on Ascaris suum pharyngeal and somatic body wall muscles were investigated. The mechanisms involved following activation of these receptors were also studied. 5-HT activated and maintained pumping in isolated pharynxes with an EC-50 value of 44±1·7μM. 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-HT₃ antagonist, ondansetron, had no effect. 5-HT and 5-HT agonists, 8-OH-DPAT, 5-carboxyamidotryptamine, α-methyl-5-HT and tryptamine all inhibited ACh-induced contractions of a somatic body wall muscle strip. Ketanserin partially blocked the inhibitory effect of α-methyl-5-HT and ACh-induced contractions while the 5-HT uptake blocker, fluoxetine, potentiated the effect of 5-HT on ACh-induced contractions. Basal levels of cAMP, 1540±232pmol/mg, in pharyngeal muscle and 1721±134pmol/mg, somatic body wall muscle, were both increased by forskolin. 5-HT had no effect on pharyngeal muscle cAMP levels but raised cAMP levels in somatic body wall muscle, e.g. 100μM 5-HT, raised the level to 2851±212pmol/mg and 1000μM raised levels to 4578±1234pmol/mg., 1000μM, increased inositol phosphate levels in pharyngeal muscle. These results provide some evidence for a 5-HT₂-like receptor on pharyngeal muscle. In contrast, the situation on somatic body wall muscle is more confusing since the pharmacological 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 the position but they must be based on the rational design of ligands specifically 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 receptors.