Influence of organic acid excretion on cuticle pH and drug absorption by Haemonchus contortus

• Published in: International journal for parasitology Vol. 26; no. 1; pp. 25 - 35
• Main Authors: Sims, S.M., Ho, N.F.H., Geary, T.G., Thomas, E.M., Day, J.S., Barsuhn, C.L., Thompson, D.P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1996; Elsevier Science
• Subjects: Absorption; absorption kinetics; Acids - metabolism; Alkalies - metabolism; Aniline Compounds - metabolism; Animals; Anthelmintics - metabolism; Benzoates - metabolism; Benzoic Acid; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; Biological Transport; cuticle; excretion kinetics; Female; Fundamental and applied biological sciences. Psychology; Haemonchus - metabolism; Haemonchus contortus; Hydrogen-Ion Concentration; Invertebrates; ivermectin; Ivermectin - metabolism; microenvironment pH; Nemathelminthia. Plathelmintha; Nitrophenols - metabolism; organic acid excretion; permeability coefficient; Physiology. Development; absorption kinetics; Haemonchus contortus; microenvironment pH; cuticle; excretion kinetics; permeability coefficient; organic acid excretion; ivermectin; Excretion; Anthelmintic; Parasite; Cuticle; Permeability; Organic acids; Absorption; Acidobasicity; Helmintha; pH; Nemathelminthia; Models; Kinetics; Invertebrata; Nematoda
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/0020-7519(95)00113-1

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 paralysed with 1 nM ivermectin.
H. contortus changed the media pH from initial values of 7.5 or 3.25 to an asymptotic value of ∼ 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 μmol/cm
2 · 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.