Influence of calcium on the effects of okadaic acid and its interaction with caffeine and theophylline in rat myometrium.
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)
Candenas
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ML
Centro de Productos Naturales Orgánicos Antonio González, Universidad de La Laguna, Tenerife, Spain.
Arteche
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Norte
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M
Advenier
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Martín
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JD
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D004347:Drug Interactions; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D007424:Intracellular Fluid / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D019319:Okadaic Acid; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000494:pharmacology*; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects
D004988:Ethers, Cyclic; D005576:Colforsin; D019319:Okadaic Acid; D002110:Caffeine; D013806:Theophylline; D010208:Papaverine; D002118:Calcium