Cell shape changes and transmembrane receptor uncoupling induced by tertiary amine local anesthetic.
Tertiary amine local anesthetics (dibucaine, tetracaine, procaine, etc.) modify cell morphology, concanavalin A (Con A)-mediated agglutinability and redistribution of Con A receptors. Con A agglutination of untransformed mouse 3T3 cells was enhanced at low concentrations of local anesthetics, and the dynamics of fluorescent-Con A indicated that ligand-induced clustering was increased in the presence of the drugs. In contast, these drugs inhibited Con A-induced receptor capping on mouse spleen cells. These effects can be duplicated by combinations of vinblastine (or colchicine) and cytochalasin B suggesting that local anesthetics act on microtubule and microfilament assemblies which are involved in the trans-membrane control of cell surface receptor mobility and distribution. It is proposed that tertiary amine local anesthetics displace plasma membrane-bound Ca2+, resulting in disengagement of microfilament systems from the plasma membrane and increased cellular Ca2+ concentration to levels which disrupt microtubular organization. The possible involvement of cellular Ca2+ in cytoskeletal destruction by local anesthetics was investigated utilizing Ca2+-specific ionophores A23187 and X537A. In media containing Ca2+ and cytochalasin B these ionophores caused effects similar to tertiary amine local anesthetics.
D000371:Agglutination / Q000187:drug effects*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D007832:Lasalocid / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects; D011343:Procaine / Q000494:pharmacology; D011952:Receptors, Concanavalin A / Q000187:drug effects*; D011955:Receptors, Drug / Q000187:drug effects*; D013748:Tetracaine / Q000494:pharmacology
D000779:Anesthetics, Local; D011952:Receptors, Concanavalin A; D011955:Receptors, Drug; D013748:Tetracaine; D003208:Concanavalin A; D000001:Calcimycin; D011343:Procaine; D003992:Dibucaine; D002118:Calcium; D007832:Lasalocid