Serotonin receptors in parasitic worms

Abstract

It is evident from the above review that during the last two decades a great deal of interest in investigating the action of serotonin in parasitic worms has been shown by parasitologists as well as by scientists from several other disciplines. What we have initially reported concerning the effect of serotonin on motility and carbohydrate metabolism of F. hepatica has been pursued on several other parasitic worms. The studies so far indicate that serotonin stimulates motility of every species tested among the phylum Platyhelminthes. The indoleamine also stimulates glycogenolysis in the few flatworm parasites that have been investigated. The information in nematodes is scanty and the role of serotonin in these parasites is still open for experimentation. Recent biochemical investigations on F. hepatica and S. mansoni demonstrated that serotonin and related compounds utilize a common class of receptors in plasma membrane particles which I designate as 'serotonin receptors'. These receptors are linked to an adenylate cyclase that catalyses the synthesis of the second messenger, cyclic 3',5'-AMP. Serotonin and its congeners increase the concentration of cyclic AMP in intact parasites whereas antagonists inhibit such an effect. Cyclic AMP stimulates glycogenolysis, glycolysis and some rate-limiting glycolytic enzymes. It activates a protein kinase that may be involved in activation of glycogen phosphorylase and phosphofructokinase. Serotonin-activated adenylate cyclase in S. mansoni is activated early in the life of the schistosomule. The possibility is discussed that the availability of cyclic AMP through serotonin activation in these parasites may be a prelude to the development processes that take place in the parasite. The different components of the serotonin-activated adenylate cyclase in the parasite are the same as those that have been previously described for the host. Binding characteristics of the receptors indicate that the receptors in F. hepatica appear to be different from those that have been described in the host. The discovery of these receptors and their differences from those in the host offer a new site which is amenable to pharmacological manipulation. The search for new agents that influence serotonin receptors in these parasites could be included in a strategy for the development of new chemotherapeutic agents against these parasites.