Abstract
The S-(−) isomers of a series of clofibric acid analogs produced only a block of chloride conductance of rat skeletal muscle fibers with increasing concentrations until block was nearly complete. The R-(+) isomers, on the other hand, at low concentrations increased chloride conductance by as much as 9% to 39% and at higher concentrations decreased chloride conductance, but never by more than 27% of the control value. The actions of the enantiomeric pairs to either produce or inhibit myotonic excitability paralleled their ability to block or increase chloride conductance, respectively.
This is a preview of subscription content, log in via an institution to check access.
References
Aberg B (1959) Some new aspects of the growth regulating effects of phenoxy compounds. In: International Conference on the Regulation of Plant Growth. Yonkers, NY, pp 199–232
Adrian RH, Bryant SH (1974) On the repetitive discharge in myotonic muscle fibers. J. Physiol. (London) 240: 505–515
Bettoni G, Loiodice F, Tortorella V, Conte-Camerino D, Mambrini, M, Ferrannini E, Bryant SH (1987) Stereospecificity of the chloride ion channel: The action of chiral clofibric acid analogues. Journal of Medicinal Chemistry 30: 1267–1270
Bretag AH (1987) Muscle chloride channels. Physiological Reviews 67: 618–724
Conte-Camerino D, Bryant SH, Lograno MD, Mambrini M (1985) The influence of inactivity on membrane resting conductances of rat skeletal muscle fibres undergoing reinnervation. J. Exp. Biol. 115: 99–104
Conte-Camerino D, Bryant SH, Mitolo-Chieppa D (1982) Electrical properties of rat extensor digitorum longus muscle after chronic application of emetine to the motor nerve. Experimental Neurology 77: 1–11
Feller DR, Kamanna VS, Newman HAI, Romstedt KJ, Witiak DT, Bettoni G, Bryant SH, Conte-Camerino D, Loiodice F, Tortorella V (1987) Dissociation of hypolipidemic and antiplatelet actions from adverse myotonic effects of clofibric acid related enentiomers. Journal of Medicinal Chemistry 30: 1265–1267
Franckowiak E, Bechem M, Schramm M, Thomas G (1985) The optical isomers of the 1,4-dihydropyridine Bay K 8644 show opposite effects on Ca channels. European Journal of Pharmacology 114: 223–226
Hof RP, Ruegg UT, Hof A, Vogel A (1985) Stereoselectivity at the calcium channel: opposite action of the enantiomers of a 1,4-dihydropyridine. Journal of Cardiovascular Pharmacology 4: 689–693
Palade PT, Barchi RL (1977) On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids. J. Gen. Physiol. 69: 879–896
Pato CN, Davis MH, Doughty MJ, Bryant SH, Gruenstein E (1983) Increased membrane permeability to chloride in Duchenne muscular dystrophy fibroblasts and its relationship to muscle function. Proc. Natl. Acad. Sci. USA 80: 4732–4736
Williams JS, Grupp IL, Grupp G, Vaghy PL, Dumont L, Schwartz A, Yatini A, Hamilton S, Brown AM (1985) Profile of the oppositely acting enantiomers of the dihydropyridine 202–791 in cardiac preparations: receptor binding, electrophysiological, and pharmacological studies. Biochemical and Biophysical Research Communications 131: 13–21
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Conte-Camerino, D., Mambrini, M., DeLuca, A. et al. Enantiomers of clofibric acid analogs have opposite actions on rat skeletal muscle chloride channels. Pflugers Arch. 413, 105–107 (1988). https://doi.org/10.1007/BF00581238
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00581238