Differential effects of maitotoxin on calcium entry and ciliary beating in the rabbit ciliated tracheal epithelium.

The marine toxin maitotoxin (MTX) induces stimulation of ciliary beating in primary cultures of rabbit tracheal epithelial cells. The response is time- and concentration-dependent. External calcium is an absolute requirement, although at a very low concentration (50 microM for maximal effect). Pretreatment of the cells with MTX induces an early (5 min) and sustained ( > or = 24 h) homologous desensitization. The response to MTX is strongly inhibited by trifluoperazin (an inhibitor of Ca-calmodulin-dependent enzymes) and by chelation of [Ca]i with BAPTA. However, the magnitude and kinetics of [Ca]i rise elicited by MTX do not correlate with those of the ciliary beat frequency (CBF) increase: the CBF increase is transient (with a peak at 5-10 min) while the [Ca]i rise is sustained; the CBF increase occurs at concentrations of MTX which are without an effect on [Ca]i; the CBF increase is not inhibited by 200 microM verapamil, genistein or okadaic acid, which inhibit the MTX-induced [Ca]i rise. The CBF increase is strongly inhibited by antagonists of arachidonic acid metabolism, mepacrine and nordiguaiaretic acid. However, MTX does not stimulate cAMP synthesis. These results suggest that calcium is not the only factor involved in the biological effects of MTX and even suggest that MTX may primarily stimulate phospholipid breakdown in the cell membrane.