6533b832fe1ef96bd129a353

RESEARCH PRODUCT

Influence of calcium on the effects of okadaic acid and its interaction with caffeine and theophylline in rat myometrium.

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The effects of okadaic acid (OA), a monocarboxylic acid produced by marine dinoflagellates belonging to the genera Dinophysis and Prorocentrum, and their interactions with theophylline and caffeine were studied on the rat-isolated uterus in a calcium-containing medium and a calcium-free medium in the presence of 10−3 M EGTA. Okadaic acid (5 × 10−6 to 5 × 10−5 M) induced a concentration-dependent contraction of the rat-isolated uterus corresponding, with 5 × 10−5M, to 142.3±6.1% (n = 7) of the contraction induced by oxytocin 10−6 M. The time to peak tension was inversely proportional to the maximum effect produced. The contraction was not sustained and was followed by a concentration-dependent decrease in tone. In a Ca2+-free medium containing 10−3 M EGTA the contractile effects of OA were significantly inhibited or reduced. A 30 min pretreatment with theophylline (3 × 10−3 M) or caffeine (2 × 10−2 M) significantly reduced, in a Ca2+-containing medium, the maximum contractile effect of OA 10−5 and/or 2 × 10−5 M and shortened the relative time to peak tension. In a Ca2+-free medium containing 10−3 M EGTA, only the second effect was observed. With a 1 min pretreatment and in a Ca2+-containing medium, theophylline 3 × 10−3 M and caffeine 10−2 M did not modify the maximum effect of OA 10−5 M but shortened the time to peak tension. The same concentrations of the xanthines potentiated the Emax of OA 5 × 10−6 M in the Ca2+-containing medium or in a Ca2+-free medium containing 10−3 M EGTA. Okadaic acid 10−6 M used as 30 min pretreatment versus OA 10−5 M and 2 × 10−5 M behaved like caffeine or theophylline. These results suggest that the OA-induced contraction of the rat uterine smooth muscle is partly effected by transmembrane calcium movements which can be inhibited in an O-Ca2+−10−3 M EGTA solution or by theophylline or caffeine. This contraction also involves mobilization of Ca2+ from an intracellular pool which is also xanthine-sensitive. The latter effect seems to be important in inducing the contractile effect. This study does not exclude the possibility of other mechanisms being involved in the contraction induced by OA.