Nature of serotonin-activated adenylate cyclase during development of Schistosoma mansoni.
The trematode Schistosoma mansoni possesses an adenylate cyclase that is stimulated by serotonin. During development from the newly transformed schistosomulum to the adult stage, the serotonin-stimulated activity of adenylate cyclase increases. Our results show that the apparent affinity of the receptor for serotonin is the same at all stages tested. Serotonin receptors were characterized by testing the ability of agonists and antagonists to influence cyclase activity. The order of potency of antagonists is similar to that seen in Fasciola hepatica and is different from that characteristic of mammalian serotonin receptors. The nature of serotonin receptors in S. mansoni appears to be unchanged during development from cercaria to adult. Forskolin, which activates adenylate cyclase at the catalytic subunit, increases cyclase activity at all stages of development with no change in affinity. Forskolin and serotonin act synergistically to activate cyclase, and the degree of potentiation is the same (four-fold) at all stages of development, indicating that the coupling between the serotonin receptor and the catalytic component of cyclase is fully developed in the schistosomulum. The synergism between serotonin and forskolin is characterized by an increase in Vmax with no effect on the affinity for either serotonin or forskolin. The Ka for potentiation of serotonin action by forskolin is lower than the Ka for direct activation of cyclase by forskolin. The change in adenylate cyclase activity during development from schistosomulum to adult does not appear to be attributable to a change in the nature of the serotonin receptor, the catalytic component, or the coupling mechanism between these two components. Instead, there appears to be an increase in the total receptor-coupled enzyme system.
Estey
S J
SJ
Department of Pharmacology, Stanford University School of Medicine, CA 94305.
Mansour
T E
TE
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D011985:Receptors, Serotonin / Q000502:physiology*; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000254:growth & development; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005576:Colforsin; D012701:Serotonin; D000262:Adenylyl Cyclases