Cell to substrate adhesion and spreading: inhibition by cationic anesthetics

The plasma membrane is the postulated site of action of anesthetics on nerve or muscle. The drugs may be useful in the analysis of membrane phenomena in other cells. We show here that cationic anesthetics and tranquilizers inhibit cell adhesion and spreading, metabolically dependent processes that involve membrane motility and changes in cell shape. Adhesion was measured by layering 51Cr labeled Sarcoma I (Sa I) cells on glass coverslips for 20 minutes at 34 degrees C, rinsing and estimating the glass-associated radioactivity. Spreading was evaluated microscopically. Both cell adhesion to untreated glass and the Mn2+ dependent adhesion to serum-coated coverslips were inhibited by the drugs, in the following order of increasing activity: tetracaine, promethazine, cyclomethycaine, chlorpromazine and fluphenazine. Similar ranks of drug activity have been reported for nerve blocking, inhibition of cell fusion and inhibition of induced spreading of macrophages. Microscopic observations showed the drugs also inhibited MN2+ INDUCED SPREADING OF Sa I. Drug treated cells were rounded, refractile, devoid of cell processes or ruffles visible by light microscopy. The effects of the drugs on adhesion and spreading were reversible upon washing of the cells. We postulate that the inhibition of adhesion and spreading are a consequence of the inhibition of cell surface motility by the anesthetics.