Local anesthetics affect transmembrane cytoskeletal control of mobility and distribution of cell surface receptors.

Tertiary amine local anesthetics facilitated concanavalin A-induced redistribution of lectin receptors on murine BALB/3T3 cells and enhanced the susceptibility of these cells to agglutination by concanavalin A. In contrast, these drugs at similar concentrations inhibited ligand-induced capping of immunoglobulin receptors on mouse lymphocytes. We propose that these differing effects of local anesthetics on membrane receptor mobility in fibroblasts and lymphocytes result from the action of anesthetics on membrane-associated microtubules and microfilaments involved in the transmembrane control of receptor mobility. We present electron microscopic evidence of structural alterations in microtubule and microfilament organization in anesthetic-treated cells, together with data on changes in the responsiveness of anesthetic-treated cells to drugs that act on microtubules and/or microfilaments. This evidence supports the proposal that anesthetics affect the organization of cytoskeletal components or their plasma membrane attachment points. The effects of local anesthetics on ligand-induced redistribution of membrane receptors in both 3T3 cells and lymphocytes can be duplicated by treating cells with colchicine (or Vinca alkaloids) together with cytochalasin B. We propose that the participation of membrane-associated microtubules and microfilaments in the transmembrane control of receptor mobility is such that microtubules and microfilaments play opposing roles in regulating the mobility and topography of cell surface receptors.