Glutamine-supported motility of adult filarial parasites in vitro and the effect of glutamine antimetabolites.
The survival in culture of adult female Brugia pahangi, Acanthocheilonema viteae, and Onchocerca volvulus and adult male Onchocerca gibsoni was assessed by measuring parasite motility. Survival of all species was maximal in a nutritionally complex medium (RPMI-1640). All species survived for up to 48 hr in a simpler medium in which the only energy source was 10 mM glutamine; motility in this medium was dependent upon pH. For the species of Onchocerca, motility was maintained better in the presence of glutamine as the sole energy source than in glucose-only medium. Motility of B. pahangi incubated in 10 mM succinate was equivalent to that seen with 10 mM glutamine, but no other tricarboxylic acid intermediate supported this parasite in vitro. Antimycin A (1 microM) and potassium cyanide (KCN, 100 microM) paralyzed B. pahangi incubated in 10 mM glutamine, an effect antagonized by glucose. KCN at 10 or 100 microM was effective also against Onchocerca gutturosa in glutamine-only medium. Several glutamine antimetabolites reduced motility of B. pahangi by 72 hr. This inhibition was prevented by 2 mM glutamine. However, the inhibition of motility in the species of Onchocerca caused by these compounds was attenuated only partially by glutamine. These data demonstrate that, under certain conditions, filarial nematodes can utilize non-sugar substrates as energy sources. The differential sensitivity seen among these organisms to mitochondrial toxins and glutamine antimetabolites may be related to the extent to which they can use these alternative substrates to generate energy.
Vande Waa
E A
EA
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Foster
L A
LA
DeRuiter
J
J
Guderian
R H
RH
Williams
J F
JF
Geary
T G
TG
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D000968:Antimycin A / Q000494:pharmacology; D017179:Brugia pahangi / Q000187:drug effects* / Q000502:physiology; D003470:Culture Media; D004153:Dipetalonema / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D009068:Movement / Q000187:drug effects; D009854:Onchocerca / Q000187:drug effects* / Q000502:physiology; D017181:Onchocerca volvulus / Q000187:drug effects / Q000502:physiology; D011190:Potassium Cyanide / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000963:Antimetabolites; D003470:Culture Media; D007555:Isoxazoles; D013449:Sulfonamides; D005973:Glutamine; C080429:JDRI 7B; C080428:JDR 004; D000968:Antimycin A; D005947:Glucose; D011190:Potassium Cyanide; C006303:acivicin