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Prostaglandin E 1 potentiation of the spontaneous phasic contraction of rat isolated portal vein by a cyclopiazonic acid‐sensitive mechanism
Author(s) -
Miwa Takaaki,
Endou Masayuki,
Okumura Fukuichiro
Publication year - 1997
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 - 10.1038/sj.bjp.0701051
Subject(s) - cyclopiazonic acid , contraction (grammar) , ryanodine receptor , chemistry , nifedipine , muscle contraction , endocrinology , medicine , prostaglandin , calcium , biophysics , endoplasmic reticulum , biochemistry , biology
The effect of prostaglandin E 1 (PGE 1 ) on the spontaneous phasic contraction of the rat isolated portal vein was studied. The isolated portal vein exhibited spontaneous phasic contractions. Removal of Ca 2+ from Krebs‐Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating that the contraction depends exclusively on Ca 2+ influx through L‐type Ca 2+ channels. On the other hand, cyclopiazonic acid (CPA), a specific inhibitor of Ca 2+ ‐ATPase of sarcoplasmic reticulum (SR) increased the amplitude of the contractions, suggesting that the SR regulates the spontaneous contractions negatively by sequestration of Ca 2+ entering through L‐type Ca 2+ channels and buffering the rise in cytosolic Ca 2+ . PGE 1 increased the amplitude of the spontaneous contraction in a concentration‐dependent manner without affecting the resting tension. The effect was completely abolished by nifedipine. Bay K 8644 and phenylephrine (PE) also increased the amplitude of the contraction in a concentration‐dependent manner. PGE 1 at a concentration of 1 μ m , Bay K 8644 at 100 n m and PE at 30 n m doubled the amplitude, respectively. Pretreatment with 1 μ m CPA abolished the effect of PGE 1 , but the effects of Bay K 8644 and PE were not inhibited by pretreatment with CPA. In contrast, 10 μ m ryanodine attenuated the effect of PE without affecting the contractile effect of PGE 1 . When the SR was depleted of Ca 2+ by repeated applications of caffeine in a nominally Ca 2+ ‐free Krebs‐Ringer solution, it took about 120 s to restore the spontaneous contraction after addition of Ca 2+ into the solution. In CPA‐treated veins, the time taken to restore the contraction was shortened significantly. Pretreatment with 1 μ m PGE 1 shortened the time to the same extent as pretreatment with CPA did. These results suggest that PGE 1 increases the amplitude of the spontaneous phasic contraction by a different mechanism from those by which PE and Bay K 8644 increase it. Inhibition of Ca 2+ ‐ATPase of the SR might be involved in the vasoactive effect of PGE 1 .British Journal of Pharmacology (1997) 120 , 1419–1426; doi: 10.1038/sj.bjp.0701051