Schistosoma mansoni: evidence for protein kinase-C-like modulation of muscle activity.
The phorbol esters, phorbol-12,13-dibutyrate, phorbol-12-myristate-13-acetate, phorbol-12,13-didecanoate, and phorbol-12,13-diacetate, as well as mezerin at concentrations as low as 10 nM produce a spastic paralysis of the schistosome musculature. The action of these protein kinase-C activators is dependent on the sites of esterification and is stereo-specific since phorbol-13,20-diacetate, phorbol-12,13,20-triacetate, 20-oxo, 20-deoxy-beta-phorbol-12,13-dibutyrate, alpha-phorbol-12,13-didecanoate, and alpha-phorbol are inactive. A phospholipid and phorbol ester-dependent protein kinase is identified. This kinase is stimulated by all of the phorbol esters that increase muscle tone but is not stimulated by phorbol esters that do not affect muscle tone. A high affinity, stereo-specific phorbol ester receptor is identified. Dose-response curves of phorbol-12,13-dibutyrate-induced muscle tension and -stimulated kinase activity and receptor binding indicate that these responses are mediated by the same system. These results indicate that protein kinase-C-like enzyme may play an important role in modulating activity of the schistosome musculature.
Blair
K L
KL
Department of Zoology, Michigan State University, East Lansing 48824.
Bennett
J L
JL
Pax
R A
RA
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D008297:Male; D009068:Movement / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide