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 beati ng in primary cultures of rabbit tracheal epithelial cells. The respon se is time- and concentration-dependent. External calcium is an absolu te requirement, although at a very low concentration (50 mu M for maxi mal effect). Pretreatment of the cells with MTX induces an early (5 mi n) and sustained (greater than or equal to 24 h) homologous desensitiz ation. 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 e licited by MTX do not correlate with those of the ciliary beat frequen cy (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 c oncentrations of MTX which are without an effect on [Ca](i); the CBF i ncrease is not inhibited by 200 mu M verapamil, genistein or okadaic a cid, which inhibit the MTX-induced [Ca](i) rise. The CBF increase is s trongly inhibited by antagonists of arachidonic acid metabolism, mepac rine and nordiguaiaretic acid. However, MTX does not stimulate cAMP sy nthesis. These results suggest that calcium is not the only factor inv olved in the biological effects of MTX and even suggest that MTX may p rimarily stimulate phospholipid breakdown in the cell membrane.