GTP binding regulatory proteins of adenylate cyclase in Schistosoma mansoni at different stages of development.

Serotonin-stimulated adenylate cyclase activity in the trematode parasite Schistosoma mansoni increases 40-50-fold during its development from newly transformed schistosomulum to adult. The role of GTP in activation of the enzyme at different stages of development was investigated. Adenylate cyclase can be activated by the non-hydrolyzable GTP analogs 5'-guanylylimidodiphosphate (GppNHp) and guanosine-5'-(3-O-thiotriphosphate) (GTP gamma S), as well as by sodium fluoride. Activation by GTP gamma S is competitively antagonized by GTP. Cholera toxin catalyzes the ADP-ribosylation of several proteins in both early schistosomula and adults. Proteins of 93 and 53 kDa are labeled in both stages, but the other proteins labeled appear to be different in the two stages. Adult schistosomes exhibit autoribosylation by cholera toxin in a broad band at 41 kDa, and this is not seen in schistosomula. The effect of cholera toxin on cyclase activity was to reduce activation by serotonin, GTP gamma S, and fluoride, all agents which act through the GTP binding protein. Cholera toxin treatment also inhibits activation by optimal levels of forskolin, a diterpene that acts at the catalytic subunit. Pertussis toxin had little effect on cyclase activity, although it catalyzed the ADP-ribosylation of a single protein band at 45 kDa in both stages. The results suggest that the GTP binding protein that mediates adenylate cyclase activation by serotonin is somewhat different from Gs in the adrenergic adenylate cyclase system. The pertussis toxin substrate in S. mansoni does not appear to function as Gi.(ABSTRACT TRUNCATED AT 250 WORDS)