The inhibitory action of okadaic acid on mechanical responses in guinea-pig vas deferens.
Okadaic acid and nifedipine inhibited contractions induced by noradrenaline (NA), KCl and ATP in guinea-pig vas deferens. NA, KCl and ATP induced initial spike-like changes followed by a sustained increase in cytosolic Ca2+ levels ([Ca2+]cyt) and tension. Okadaic acid inhibited the sustained increments in [Ca2+]cyt and muscle tension due to NA and ATP more than the initial spike-like changes, whereas nifedipine more strongly inhibited the initial spike changes. Okadaic acid also inhibited the KCl-induced contraction with only a small inhibition of the stimulated [Ca2+]cyt. By contrast, nifedipine (10(-7) M) inhibited the increments in both [Ca2+]cyt and muscle tension due to KCl. Okadaic acid markedly inhibited the maximal contractile response to Bay K 8644 but nifedipine only shifted the response curve to the right without affecting the maximum responses. In a Ca2(+)-free medium containing EGTA and nifedipine, okadaic acid did not inhibit the residual phasic contractile response to NA (10(-4) M) but the contractile response to a subsequent addition of Ca2+ (1.2 mM) was suppressed. These results suggest that, in guinea-pig vas deferens, okadaic acid has an inhibitory effect on smooth muscle contraction but not on the intracellular Ca2+ mobilization. The inhibitory effect may be due to the inhibition of Ca2+ influx and the possible interference of contractile elements.
Shibata
S
S
Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu 96822.
Satake
N
N
Morikawa
M
M
Kown
S C
SC
Karaki
H
H
Kurahashi
K
K
Sawada
T
T
Kodama
I
I
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D019319:Okadaic Acid; D011189:Potassium Chloride / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004988:Ethers, Cyclic; D014662:Vasoconstrictor Agents; D019319:Okadaic Acid; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine