Dual roles of phorbol 12, 13-dibutyrate in the regulation of guinea-pig gastric contraction
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概要
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We performed experiments to investigate the actions of protein kinase C(PKC) on mechanical contraction during agonist stimulation in guinea-pig stomach. We used carbachol and high K condition to enhance mechanical contraction by mobilizing intracellular Ca^<+2> and increasing Ca^<+2> influx through voltage-dependent Ca^<+2> channel, respectively. Phorbol 12, 13-dibutyrate (PDBu) increased spontaneous contractions sensitive to verapamil (438±82.2%, n=7) and potentiated high K-induced contraction (189±22.5%, n=5). However, carbachol (CCh)-induced contractions in PDBu-treated condition depended on extracellular Ca^<+2>. In the presence of extracellualr Ca^<+2>, CCh-induced contraction was potentiated, while it was suppressed in the absence of extracellular Ca^<+2> in Ca^<+2>-preloaded muscle strips. To prove the hypothesis that such phenomena might be related with changes of myopldsmic Ca^<+2> concentration, we investigated the effect of PDBu on voltage-dependent Ca^<+2> current(I_<ca>) and CCh-induced Ca^<+2>-activated K current(I_<k(ca)>) transient using whole-cell voltage clamp technique. For recording voltage-dependent Ca^<+2> current(Ica), 10 mM Ba^<+2>, instead of Ca^<+2>, was used to enhdnce the current size. Voltage-dependent Ba^<+2> current(I_<Ba>) was increased by PDBu (212±32.2% of steady state currents, n=5), while CCh-induced increase of I_<k(ca)> transient was inhibited by PDBu (n=5), the changes of which were similar to those of muscle contractions. To analyze the steps involved in the inhibition of CCh-induced I_<k(ca)> transient by PDBu, we investigated the effect of PDBu on I_<k(ca)> in the cells perfused with Ins (1,4,5)P_3. However, Ins (1,4,5)P_3-induced I_<k(ca)> was not inhibited by the treatment with phorbol ester. From these results, it is concluded that inhibition of phosphatidylinositol-phospholipase C(PI-PLC) system and potentiation of Ica by PKC are important regulatory mechanisms in agonist-induced muscle contraction.
- 日本平滑筋学会の論文
著者
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Kim Sung
Department of Bioengineering and Technology, College of Engineering, Kangwon National University
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Kim Ki
Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Oral Science Res
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So Insuk
Department of Physiology, Seoul National University College of Medicine
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Kim Ki
韓国
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Kim K
Department Of Physiology School Of Medicine Gachon University Of Medicine And Science
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Kim Y
Seoul National Univ. Seoul Kor
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Kim Young
Department Of Electronics Engineering Korea Advance Intitute Of Science & Technology
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So Insuk
Department Of Physiology Seoul National University College Of Medicine
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So Insuk
Department Of Physiology And Biophysics Seoul National University College Of Medicine
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Kim Ki
Department Of Physiology School Of Medicine Gachon University Of Medicine And Science
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Kim Sung
Department Of Physiology Seoul National University College Of Medicine
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Kim Young
Department Of Agricultural Chemistry The University Of Tokyo
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Kim Sung
Department Of Anatomy
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Kim Young
Department Of Physiology And Biophysics Seoul National University College Of Medicine
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AHN Seung
Department of Dermatology, College of Medicine, Chung Ang University Hospital
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Kim S
Department Of Physiology Seoul National University College Of Medicine
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Ahn Seung
Department Of Rhysiology & Biophysics Seoul National University College Of Medicine
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Ahn Seung
Department Of Dermatology College Of Medicine Chung Ang University Hospital
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Kim Ki
Deparment Of Obstetrics & Gynecology College Of Medicine Pusan National University
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Kim Young
Coll. Of Pharmacy And Res. Inst. Of Pharmaceutical Sci. Seoul National Univ.
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Kim Sung
Department of Advanced Materials Engineering for Information and Electronics, Kyung Hee University, Yongin, Gyeonggi 446-701, Republic of Korea
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