Parasitology



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


J.E.  TRIM  a1, L.  HOLDEN-DYE  a1, J.  WILLSON  a1, M.  LOCKYER  a2 and R.J.  WALKER  a1 c1
a1 School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
a2 University College London, Cruciform Project, 140 Tottenham Court Road, London WIP 9LN, UK

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.

(Received April 1 2000)
(Revised July 27 2000)
(Accepted August 8 2000)


Key Words: 5-hydroxytryptamine; Ascaris suum; nematode; acetylcholine; cAMP.

Correspondence:
c1 Corresponding author: School of Biological Sciences, Biomedical Sciences Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX. Tel: +02380 594343. Fax: +02380 594319. E-mail: rjwalker@soton.ac.uk


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