No abstract

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 x 10(-6) to 5 x 10(-5) M) induced a concentration-dependent contraction of the rat-isolated uterus corresponding, with 5 x 10(-5) M, 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 Ca(2+)-free medium containing 10(-3) M EGTA the contractile effects of OA were significantly inhibited or reduced. A 30 min pretreatment with theophylline (3 x 10(-3) M) or caffeine (2 x 10(-2) M) significantly reduced, in a Ca(2+)-containing medium, the maximum contractile effect of OA 10(-5) and/or 2 x 10(-5) M and shortened the relative time to peak tension. In a Ca(2+)-free medium containing 10(-3) M EGTA, only the second effect was observed. With a 1 min pretreatment and in a Ca(2+)-containing medium, theophylline 3 x 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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 microM in normal physiological solution was unaffected in the presence of tetrodotoxin (10 microM), indomethacin (3 microM), 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 microM) which completely or highly blocked the response to KCl (60 mM), oxytocin (1 microM), or acetylcholine (100 microM). In a Ca(2+)-free 1 mM EGTA-containing solution, the response to 10 and 20 microM OA was slightly but significantly reduced whereas the response to 5 microM OA was abolished. However, a response similar to that evoked in Ca(2+)-containing solution was observed when 5 microM OA was added to the bath in the presence of 1 microM oxytocin or 160 microM vanadate in a Ca(2+)-depleted solution with 1 mM EGTA. These data suggest that the response of rat myometrium to OA (> or = 5 microM) is not mediated through activation of membrane receptors or neurotransmitter release nor by cyclo-oxygenase products. The response to OA (10 and 20 microM) is highly resistant to the absence of calcium in the medium and does not seem to involve calcium entry through dihydropyridine-sensitive Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

1. In order to gain information on the effect of protoporphyrin IX on changes in the properties of the canalicular plasma membrane, we studied the release of canalicular membrane constituents, namely phospholipids, cholesterol and 5'-nucleotidase, into bile in anaesthetized rats receiving saline or taurocholate (0.5 mumol min-1 100 g-1 body weight) with or without protoporphyrin IX infusion (10 or 20 micrograms min-1 100 g-1 body weight). 2. Protoporphyrin IX induced an impairment of spontaneous bile flow and of biliary secretion of cholesterol, phospholipids and bile acids. The taurocholate-induced increase in bile acid output was not significantly reduced by protoporphyrin IX at either of the doses used. However, when a cholestatic dose of protoporphyrin IX was infused, the taurocholate-induced bile flow and secretion of lecithin and cholesterol were significantly reduced. 3. Biliary output of phospholipid species other than lecithin did not counterbalance the protoporphyrin IX-induced reduction in biliary lecithin secretion. Biliary outputs of both total phospholipid and lecithin were inhibited by protoporphyrin IX to similar extents. 4. Protoporphyrin IX alone had no effect on the biliary release of 5'-nucleotidase, whereas when it was given with taurocholate, it increased the bile acid-induced biliary output of this enzyme markedly. 5. In summary, these results indicate that protoporphyrin IX impairs the biliary secretion of phospholipids and cholesterol but not that of bile acid. The release of canalicular membrane constituents other than lipids was also modified by protoporphyrin IX.