CHANGES IN MORPHOLOGY OF HUMAN SKIN FIBROBLASTS INDUCED BY LOCAL-ANESTHETICS - ROLE OF ACTOMYOSIN CONTRACTION

Local anaesthetics block action potentials in the membranes of excitab le cells but their effects on non-excitable cells are less well known. Some local anaesthetics are applied directly onto the skin, and for t his reason the effect of procaine (p-aminobenzoic acid diethylamino-et yl eater hydrochloride) and tetracaine (4-[butylamino]benzoic acid 2-[ dimethylamino]ethyl ester) upon the morphology and cytoskeleton organi sation of human skin fibroblasts was investigated. The time lapse vide o recording of fibroblasts cultured in serum-enriched medium revealed that the cells rapidly change shape after the addition of the anaesthe tic. These effects were fully reversible. The microscopic observations were confirmed by quantitative analysis of projected cell area and ce ll shape parameters. Local anaesthetics significantly changed the acti n cytoskeleton organisation, inducing total disappearance of stress fi bres. Serum-starvation or myosin light chain kinase inhibitors, KT 592 6 inhibitor (8 R ,9S *,11S 9-hydroxy-9-methoxycarbonyl-8-methyl-14-n- propoxy- 2,3,9,10-tetrahydro-8,11-epoxy,1 H,8 H,11 ,11a-triazadibenzo[ a,g]cycloocta[cde]trinden-1-one or wortmannin, which induce the 'relax ed' morphology of the cells, prevent both the anaesthetic-induced chan ges in cell shape and the disassembly of stress fibres. Together, the observations suggest that local anaesthetics affect the actomyosin sys tem, inducing contraction. (C) 1998 Elsevier Science B.V. All rights r eserved.