THE METALLOPROTEASE INHIBITOR 1,10-PHENANTHROLINE AFFECTS SCHISTOSOMA-MANSONI MOTOR-ACTIVITY, EGG-LAYING AND VIABILITY

The Zn2+-chelating metalloprotease inhibitor 1,10-phenanthroline (phen anthroline, 5-150 mu M) elicited dose-dependent contraction of the lon gitudinal and circular (transverse) musculature of adult male schistos omes. At the same concentrations, phenanthroline did not cause contrac tion of dispersed individual muscle fibres. The phenanthroline-induced contractions were reduced by the inclusion of 100 or 300 mu M Zn2+ in the extracellular medium. Phenanthroline (05-150 mu M) also inhibited the egg production of adult worm pairs in vitro, with a 98% reduction at 50 mu M. When worm pairs were exposed to phenanthroline, the males detached from the dish and released the females, resulting in unpaire d worms. At the higher concentrations (50 and 150 mu M), the worms wer e killed in vitro. Worm burdens were reduced by over 50% in infected m ice injected with phenanthroline (20 mg/kg/day for 4 days), but twice the dose resulted in only a 25% reduction. Phenanthroline injections a lso induced an hepatic shift and an unpairing of adult worms in infect ed mice, and the female worms appeared degenerate and lacked gut pigme ntation. Mice fed a diet containing 0.3% phenanthroline received signi ficant protection from infection when challenged with schistosome cerc aria, where phenanthroline-fed mice had 94% fewer adult worms than con trol mice. The broad range of phenanthroline effects on schistosomes s uggests broad and important functions for metalloproteases in these wo rms.