Molecular Pharmacology, Vol 16, 202-214, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Monovalent Ionophores Inhibit Acetylcholinesterase Release from Cultured Chick Embryo Skeletal Muscle Cells

¹ Department of Pharmacology, University of Connecticut Health Center, Farmington, Connecticut 06032

Acetylcholinesterase (ACHE) is a glycoprotein that is released in large amounts from embryonic chick muscle in vivo and in vitro. We show in this paper that the ionophores that transport monovalent cations and divalent cations markedly affect the accumulation and release of ACHE. ACHE release can be stimulated by low levels of the calcium ionophore A23187 and inhibited by low levels of the carboxylic ionophores which transport monovalent cations. Release of ACHE is inhibited 50% by 0.1 µM Monensin, or 0.05 µM Nigericin and is stimulated maximally by 0.05-0.1 µM A23187. The inhibition of ACHE release by the ionophores and the accompanying accumulation of ACHE activity in the cell is rapid and reversible; the inhibition of ACHE release by the ionophores is not due to an overall inhibition of protein synthesis.

The ionophores Monensin and Nigericin cause large membranous vesicles to appear in the vicinity of the muscle nucleii. These appear at ionophore concentrations that are 50 to 500 times lower than those previously reported to swell the Golgi of smooth muscle and immunoglobulin secreting cells. The possibility is raised that the membranous vesicles we observe after ionophore treatment are also derived from the golgi of skeletal muscle and represent sites of intracellular ACHE accumulation and transport.

Note:
ACKNOWLEDGMENTS We would like to thank the University of Connecticut Electron Microscopy Facility for performing the electron microscopy. We would like to thank Ms. Patrice Favreau and Ms. Rita Laraia for their excellent technical assistance.

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