Filarial parasites exhibit unusually high levels of choline acetyltransferase activity.
The presence of unusually high levels of choline acetyltransferase (ChAT, EC 2.3.1.6) in human and animal filarial parasites has been demonstrated. The levels of ChAT were highest in male worms of Brugia malayi and Brugia pahangi, with specific activities in crude extracts of about 2.27 and 1.26 mumol min-1 (mg protein)-1, respectively. The enzyme levels in these worms were over 10-20 times higher than in male worms of Litomosoides carinii. The ChAT levels were about 2-5 times higher in male than in female worms. The enzyme was also present in appreciably high levels in microfilariae of Brugia species, L. carinii and Wuchereria bancrofti. The levels of ChAT in male worms of Brugia species were several thousand-fold higher than in the intestinal nematodes Trichuris muris and Necator americanus, and were over three orders of magnitude higher than in mammalian brain. Unlike the mammalian ChAT, the parasite enzyme was extremely stable. The parasite enzyme was not inhibited by any of the antifilarial agents except suramin. The filarial ChAT was strongly inhibited by sulphydryl reagents and diethylpyrocarbonate. Ethacrynic acid (EA), a diuretic and a sulphydryl reagent, irreversibly inhibited the filarial ChAT activity at low concentrations. In contrast, EA inhibited the activity of mammalian brain ChAT at much higher concentrations. The motility of adult worms and microfilariae was irreversibly inhibited by low concentrations of EA. Furthermore, the inhibition of motility was paralleled by the inactivation of ChAT in these parasites. These studies indicate that ChAT activity appears to be vital for parasite's survival and that acetylcholine might play a key role in the control of worm motility.
Swamy
K H
KH
Research Centre, Pharma Division, Hindustan Ciba-Geigy Ltd., Bombay, India.
D000110:Acetylcholinesterase / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000201:enzymology; D002009:Brugia / Q000201:enzymology*; D002417:Cattle; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005370:Filarioidea / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008297:Male; D009068:Movement; D009331:Necator / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D051381:Rats; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D014258:Trichuris / Q000201:enzymology; D014957:Wuchereria / Q000201:enzymology*; D014958:Wuchereria bancrofti / Q000201:enzymology*
D013439:Sulfhydryl Reagents; D013498:Suramin; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase