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Effects of okadaic acid on cytosolic calcium concentrations and on contractions of the porcine coronary artery
Author(s) -
Hirano Katsuya,
Kanaide Hideo,
Nakamura Motoomi
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12672.x
Subject(s) - okadaic acid , calcium , medicine , cytosol , chemistry , endocrinology , muscle contraction , cardiology , biochemistry , phosphatase , phosphorylation , enzyme
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 Ca 2+ concentration ([Ca 2+ ] i ) and tension developed in porcine coronary arterial strips loaded with fura‐2. 2 Both in the presence (1.25 m m ) and absence of extracellular Ca 2+ , 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 [Ca 2+ ] i , only in the presence of extracellular Ca 2+ . 3 At a lower concentration that did not cause contraction or increase [Ca 2+ ] i , OA (10 −6 m ) inhibited tension development but not the Ca 2+ transient on readmission of Ca 2+ in 118 mM K + ‐depolarizing solution. OA inhibited the maximum levels of the developed tension, without affecting the K D 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 Ca 2+ and without any changes in [Ca 2+ ] i . Lower concentrations of OA inhibit the Ca 2+ ‐dependent contractions. The lack of effect on K D values suggests that the [Ca 2+ ] i ‐sensitivity of the contractile apparatus is not affected by this inhibition of contraction.