Effects of okadaic acid on cytosolic calcium concentrations and on contractions of the porcine coronary artery.
1. We investigated the effects of okadaic acid (OA), a phosphatase inhibitor derived from a 38-carbon fatty acid and isolated from the black sponge, genus Halichondria, on cytosolic Ca2+ concentration ([Ca2+]i) and tension developed in porcine coronary arterial strips loaded with fura-2. 2. Both in the presence (1.25 mM) and absence of extracellular Ca2+, OA (over 10(-6) M) induced a concentration-dependent, slow and progressive increase in tension. Calcium removal had no effect on the maximum level of tension, time between application of the drug and the onset of tension, or the time required to reach the maximum tension. However, there was a slight concentration-dependent increase in [Ca2+]i, only in the presence of extracellular Ca2+. 3. At a lower concentration that did not cause contraction or increase [Ca2+]i, OA (10(-6) M) inhibited tension development but not the Ca2+ transient on readmission of Ca2+ in 118 mM K+-depolarizing solution. OA inhibited the maximum levels of the developed tension, without affecting the KD value (598 +/- 204 nM for control vs 678 +/- 464 nM after OA treatment) or the Hill coefficient (1.78 +/- 0.10 for control vs 1.98 +/- 0.47 for OA treatment). 4. It is concluded that high concentrations of OA induce a contraction independent of extracellular Ca2+ and without any changes in [Ca2+]i. Lower concentrations of OA inhibit the Ca2+-dependent contractions. The lack of effect on KD values suggests that the [Ca2+]i-sensitivity of the contractile apparatus is not affected by this inhibition of contraction.
Hirano
K
K
Division of Molecular Cardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Japan.
Kanaide
H
H
Nakamura
M
M
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005470:Fluorometry; D016257:Fura-2; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid; D011188:Potassium / Q000494:pharmacology; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001572:Benzofurans; D004988:Ethers, Cyclic; D014662:Vasoconstrictor Agents; D019319:Okadaic Acid; D011188:Potassium; D002118:Calcium; D016257:Fura-2