SPASMOLYTIC ACTIVITY OF A LIPIDIC EXTRACT FROM SABAL SERRULATA FRUITS- FURTHER STUDY OF THE MECHANISMS UNDERLYING THIS ACTIVITY

The mechanisms involved in the spasmolytic effect of a lipidic extract from Sabal serrulata fruits were investigated. The extract relaxed va nadate-induced contractions on rat uterus incubated in a calcium free solution (EC(50) = 11.41 +/- 1.38 mu g/ml). The modification of the ef fect by a cyclooxygenase inhibitor (indomethacin), a protein kinase A inhibitor (TPCK), calcium modifying drugs, and drugs interfering with transcription and protein synthesis has been assayed. The effect was u nmodified by a 3 mu M concentration of indomethacin, (EC(50) = 8.77 +/ - 1.28 vs 11.41 +/- 1.38 mu g/ml) and a 5 mu g/ml concentration of the transcription inhibitor, actinomycin D, (EC(50) = 8.23 +/- 2.19 vs 11 .41 +/- 1.38 mu g/ml). The inhibitor of intracellular calcium mobiliza tion TMB-8 (0.1 mM), the Na+/Ca++ exchanger inhibitor amiloride (0.1 m M), the calcium chelator BAPTA-AM (50 mu M), the PKA inhibitor TPCK (1 0 mu M), and the protein synthesis inhibitor cycloheximide (10 mu g/ml ) significantly shifted to the right the dose-response curve of the ex tract (EC(50) = 17.83 +/- 1.87 mu g/ml, 18.61 +/- 2.50 mu g/ml, 35.28 +/- 9.13 mu g/ml, 33.99 +/- 3.07 mu g/ml, and 27.31 +/- 4.93 mu g/ml, respectively, vs 11.41 +/- 1.38 mu g/ml). These results suggest that t he effect of the lipidic extract from S. serrulata fruits could be par tially due to Na+/Ca++ exchanger activation and interference with intr acellular calcium mobilization, and point to cAMP as a possible mediat or. Moreover, protein synthesis seems to be involved in the spasmolyti c activity.