Evidence for the involvement of the cyclooxygenase-metabolic pathway in diclofenac-induced inhibition of spontaneous contraction of rat portal vein smooth muscle cells.
The effects of diclofenac, a cyclooxygenase (COX) inhibitor, were investigated on spontaneous phasic contractions of longitudinal preparations of the rat portal vein. Diclofenac produced a concentration-dependent decrease in the amplitude of these spontaneous phasic contractions. Diclofenac (30 microM) decreased the amplitude of the spontaneous phasic increase in the F340/F380 ratio of Fura PE3, an indicator of intracellular Ca2+ concentration. It also reduced the number of action potentials in each burst discharge without changing the resting membrane potential of longitudinal smooth muscle cells. The extent of the distribution of Lucifer Yellow injected into a smooth muscle cell was decreased in the presence of diclofenac (30 microM). Both AH6809, a prostanoid EP receptor antagonist, and SQ22536, an adenylate cyclase inhibitor, decreased the amplitude of the spontaneous contractions. On the other hand, neither ozagrel, a thromboxane synthase inhibitor, nor SQ29548, a prostanoid TP receptor antagonist, significantly affected spontaneous contractions. These results indicate that diclofenac inhibits the amplitude of spontaneous contractions of the rat portal vein through inhibition of electrical activity, which may be related to an inhibition of the cyclooxygenase pathway.
Shimamura
Keiichi
K
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan. shimamu@hoku-iryo-u.ac.jp
Kimura
Shinichi
S
Zhou
Ming
M
Wang
Yue
Y
Toba
Miyuki
M
Ohashi
Atsuko
A
Higuchi
Takashiro
T
Kawaguchi
Hideaki
H
Kitamura
Kenji
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007425:Intracellular Membranes / Q000378:metabolism; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D009712:Nucleotides, Cyclic / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009994:Osmolar Concentration; D011169:Portal Vein / Q000378:metabolism / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D005456:Fluorescent Dyes; D007546:Isoquinolines; D009712:Nucleotides, Cyclic; D011982:Receptors, Prostaglandin; D013931:Thromboxanes; D004008:Diclofenac; C017475:lucifer yellow; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium