title: Influence of organic acid excretion on cuticle pH and drug absorption by Haemonchus contortus.
abstract: To determine if a cuticle microenvironment pH is maintained by adult Haemonchus contortus, organic acid excretion kinetics and absorption kinetics of selected model weak acids and a weak base were measured in incubation media that varied in buffer capacity (0.25-20 mM HEPES or 5 mM glycine) and initial pH (7.5 or 3.5). To evaluate the importance of the cuticle as a pathway for organic acid excretion and drug absorption the pharynx was paralyzed with 1 nM ivermectin. H. contortus changed the media pH from initial values of 7.5 or 3.25 to an asymptotic value of approximately 5.6. The rate of pH change depended on the buffer capacity, but was not affected by chemical ligation with ivermectin. The intrinsic rate of excretion of organic acids (0.045 +/- 0.016 micromol/cm2 x h) was constant during the first 8-12 h of incubation and was independent of initial pH, buffer capacity or ivermectin ligation. The rates of absorption of the model weak acids, benzoic acid and p-nitrophenol, and the model weak base, aniline, were not affected by initial pH, buffer capacity or ivermectin ligation. These results suggest that H. contortus excretes organic acid endproducts of carbohydrate metabolism across its cuticle, and that these acids maintain a microenvironment pH within the water-filled pores of the cuticle that controls the rate of adsorption of weakly acidic or basic drugs.
authors.affiliation: Upjohn Laboratories, Kalamazoo, MI 49001, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Sims
authors.forename: N F
authors.initials: NF
authors.lastname: Ho
authors.forename: T G
authors.initials: TG
authors.lastname: Geary
authors.forename: E M
authors.initials: EM
authors.lastname: Thomas
authors.forename: J S
authors.initials: JS
authors.lastname: Day
authors.forename: C L
authors.initials: CL
authors.lastname: Barsuhn
authors.forename: D P
authors.initials: DP
authors.lastname: Thompson
mesh_terms: D000042:Absorption; D000143:Acids / Q000378:metabolism; D000468:Alkalies / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism; D001565:Benzoates / Q000378:metabolism*; D019817:Benzoic Acid; D001692:Biological Transport; D005260:Female; D006189:Haemonchus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007559:Ivermectin / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism*
chemical_list: D000143:Acids; D000468:Alkalies; D000814:Aniline Compounds; D000871:Anthelmintics; D001565:Benzoates; D009596:Nitrophenols; D007559:Ivermectin; D019817:Benzoic Acid; C023650:aniline; C024836:4-nitrophenol