Mechanisms of Microenvironmental pH Regulation of the Cuticle and Implications for Transcuticular Transport in Ascaris Suum
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|Ho, Norman F.H.
|Thompson, David P.
|Magas, Louis T.
|vii, 79 p.
|The cuticle and gut of gastrointestinal nematodes are the major interfaces between the parasite and its host animal. Previous in vitro studies by Ho et al. (1990) have shown. that model solutes are transported across the cuticle of Ascaris suum depending on their molecular size, charge, pKa, and intrinsic lipid-water partition coefficient. Recent work with whole A. suum has indicated that the pH of the cuticle may be different from that of the bathing medium. Therefore, in this study, the presence of a microenvironmental pH in the cuticle of live, intact A. suum was probed using closed and open perfusion systems. The effects of microenvironmental pH on parasite absorption of p-nitrophenol were examined, and the compounds responsible for the pH change were identified. The results demonstrate that A. suum excretes the volatile fatty acids acetate, butyrate, 2-methylbutyrate, valerate, and 2-methylvalerate. These organic anions (pKa approximately 4.8 for each) are excreted through the cuticle, and cause the pH of the medium in the vicinity of the cuticle to change until reaching the pKa of these acids. The pH change was insensitive to N2/C02 atmosphere, initial buffer pH, oral and anal ligation, and the presence of the Na+/H+ exchange inhibitor, amiloride. The uptake of p-nitrophenol (pKa 7.2) by A. suum was unaffected by the initial buffer pH, ionic strength, and pH changes during the course of 24 hour incubation. These results suggest that the amount of weak acid or weak base drug available for absorption will be a function of the microenvironmental pH of the cuticle rather than the pH of the gastrointestinal tract of the host animal.
|Drug Delivery Systems Research. Upjohn Company. Kalamazoo, Michigan.
|Animal Health Therapeutics. Upjohn Company. Kalamazoo, Michigan.
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|Mechanisms of Microenvironmental pH Regulation of the Cuticle and Implications for Transcuticular Transport in Ascaris Suum