CALCIUM-DEPENDENCE OF THE MECHANICAL RESPONSE EVOKED BY OKADAIC ACID IN SMOOTH-MUSCLE

The effects of okadaic acid (OA), obtained from a culture of the marin e dinoflagellate Prorocentrum lima were studied on isolated strips of rat myometrium. The contractile response evoked by OA at 5, 10, and 20 mu M in normal physiological solution was unaffected in the presence of tetrodotoxin (10 mu M), indomethacin (3 mu M), or a cocktail of ant agonists which blocked muscarinic, adrenergic, histaminergic, serotone rgic, and opioid receptors. Similarly, the response to OA was unaffect ed in the presence of nifedipine at a concentration (1 mu M) which com pletely or highly blocked the response to KCl (60 mM), oxytocin (1 mu M), or acetylcholine (100 mu M). In a Ca2+-free 1 mM EGTA-containing s olution, the response to 10 and 20 mu M OA was slightly but significan tly reduced whereas the response to 5 mu M OA was abolished. However, a response similar to that evoked in Ca2+-containing solution was obse rved when 5 mu M OA was added to the bath in the presence of 1 mu M ox ytocin or 160 mu M vanadate in a Ca2+-depleted solution with 1 mM EGTA . These data suggest that the response of rat myometrium to OA (greate r than or equal to 5 mu M) is not mediated through activation of membr ane receptors or neurotransmitter release nor by cyclo-oxygenase produ cts. The response to OA (10 and 20 mu M) is highly resistant to the ab sence of calcium in the medium and does not seem to involve calcium en try through dihydropyridine-sensitive Ca2+ channels. However, our resu lts also show that the response evoked by OA is not completely indepen dent of extracellular calcium and/or calcium accessible to EGTA and su ggest that a minimal activation of a Ca2+-dependent mechanism is neces sary for OA to be effective.