Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 171, Issue 1, Pages 1-7Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2009.12.007
Keywords
Ascaris suum; Levamisole; Contraction; Ryanodine; Caffeine; AF2
Categories
Funding
- national Institute of Allergy and Infectious Diseases [R 01 AI 047194]
- Iowa Center for Advanced Neurotoxicology
Ask authors/readers for more resources
Cholinergic anthelmintics (like levamisole) are important drugs but resistance with reduced responses by the parasite to these compounds is a concern. There is a need to study and understand mechanisms that affect the amplitude of the responses of parasites to these drugs. In this paper, we study interactions of levamisole and ryanodine receptors on contractions of Ascaris suum body muscle flaps. In our second paper, we extend these observations to examine electrophysiological interactions of levamisole, ryanodine receptors (RyRs) and AF2. We report that the maximum force of contraction, g(max), was dependent on the extracellular concentration of calcium but the levamisole EC50 (0.8 mu M) was not. The relationship between maximum force of contraction and extracellular calcium was described by the Michaelis-Menten equation with a K-m of 1.8 mM. Ryanodine inhibited g(max) without effect on EC50; ryanodine inhibited only 44% of the maximum contraction (K-i of 40 nM), revealing a ryanodine-insensitive component in the levamisole excitation-contraction pathway. Dantrolene had the same effect as ryanodine but was less potent. The neuropeptide AF2 (1 mu M) decreased the levamisole EC50 to 0.2 mu M without effect on g(max); 0.1 mu M ryanodine and 100 mu M dantrolene, inhibited the g(max) of the AF2-potentiated levamisole response. High concentrations of caffeine, 30 mM, produced weak contraction of the body-flap preparation. Caffeine behaved like ryanodine in that it inhibited the maximum force of contraction, g(max) without effects on the levamisole EC50. Thus, RyRs play a modulatory role in the levamisole excitation-contraction pathway by affecting the maximum force of contraction without an effect on levamisole EC50. The levamisole excitation-contraction coupling is graded and has at least two pathways: one sensitive to ryanodine and one not. (C) 2010 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available