Lysophosphatidic acids induce contraction of rat isolated colon by two different mechanisms

Lysophosphatidic acids (1-linoleoyl-, 1-linolenoyl, 1-arachidonoyl- and 1-O-hexadecyl-sn-glycero-3-phosphate) induced rapid contraction of rat isolated colon which was dependent on external Ca2+, 1-linolenoyl-lysophosphatidic acid having the greatest effect. The contraction induced by 1-linolenoyl-lysophosphatidic acid was reduced considerably by nifedipine and verapamil, but not by atropine or indomethacin. Phosphatidic acids with two short-chain acyl groups induced a small, atropine-sensitive contraction at 100 microM, but phosphatidic acids with two long-chain acyl groups were inactive. These results suggest that unlike phosphatidic acids, lysophosphatidic acids act directly on extracellular sites of the plasma membrane of smooth muscle cells in rat colon, mainly through activation of voltage-sensitive Ca2+ channels.