Related Experiment Videos
Calcium dependence of the mechanical response evoked by okadaic acid in smooth muscle
E Arteche1, M P Ausina, J D Martin
1Departament de Farmacología, Facultat de Farmacia, Universitat de València, Spain.
Abstract:
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)
Insights
Okadaic acid (OA) causes contractions in rat myometrium independent of nerve signals or common receptors. While calcium is needed for low OA doses, higher doses show resistance to calcium deprivation, suggesting a unique mechanism.
Area of Science:
- Pharmacology
- Marine Toxin Research
- Reproductive Physiology
Background:
- Okadaic acid (OA) is a marine toxin produced by dinoflagellates.
- Rat myometrium is a key tissue in reproductive physiology.
Purpose of the Study:
- To investigate the mechanism of action of okadaic acid (OA) on isolated rat myometrium contractions.
- To determine if OA-induced contractions involve neurotransmitter release, receptor activation, or specific ion channels.
Main Methods:
- Isolated rat myometrium strips were exposed to varying concentrations of okadaic acid (OA).
- Contractile responses were measured in the presence of receptor antagonists, tetrodotoxin, indomethacin, and nifedipine.
- Experiments were conducted in calcium-free solutions with EGTA to assess calcium dependency.
Main Results:
- OA-induced contractions were unaffected by receptor antagonists, tetrodotoxin, or indomethacin.
- Responses to OA were largely unaffected by nifedipine, which blocked KCl, oxytocin, and acetylcholine responses.
- Contractions to 10 and 20 microM OA showed resistance to calcium absence, while 5 microM OA required calcium.
Conclusions:
- OA-induced myometrium contractions are not mediated by common receptors, neurotransmitter release, or cyclo-oxygenase products.
- The mechanism for higher OA concentrations (10-20 microM) is largely independent of extracellular calcium.
- OA's action on myometrium may involve calcium entry through non-dihydropyridine-sensitive channels or other pathways.