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RESEARCH PRODUCT

Calcium Dependence of the Mechanical Response Evoked by Okadaic Acid in Smooth Muscle

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The effects of okadaic acid (OA), obtained from a culture of the marine dinoflagellate Prorocentrum Lima were studied on isolated strips of rat myometrium. The contractile response evoked by OA at 5, 10, and 20 μM in normal physiological solution was unaffected in the presence of tetrodotoxin (10 μM), indomethacin (3 μM), or a cocktail of antagonists which blocked muscarinic, adrenergic, histaminergic, serotonergic, and opioid receptors. Similarly, the response to OA was unaffected in the presence of nifedipine at a concentration (1 μM) which completely or highly blocked the response to KCl (60 mM), oxytocin (1 μM), or acetylcholine (100 μM). In a Ca 2+ -free 1 mM EGTA-containing solution, the response to 10 and 20 μM OA was slightly but significantly reduced whereas the response to 5 μM OA was abolished. However, a response similar to that evoked in Ca 2+ -containing solution was observed when 5 μM OA was added to the bath in the presence of 1 μM oxytocin or 160 μM vanadate in a Ca 2+ -depleted solution with 1 mM EGTA. These data suggest that the response of rat myometrium to OA (≥5 μM) is not mediated through activation of membrane receptors or neurotransmitter release nor by cyclo-oxygenase products. The response to OA (10 and 20 μM) is highly resistant to the absence of calcium in the medium and does not seem to involve calcium entry through dihydropyridine-sensitive Ca 2+ channels. However, our results also show that the response evoked by OA is not completely independent of extracellular calcium and/or calcium accessible to EGTA and suggest that a minimal activation of a Ca 2+ -dependent mechanism is necessary for OA to be effective