Molecular Mechanism of Action by Atrial Natriuretic Peptide in Rat Vascular Smooth Muscle Cells : SYMPOSIUM ON ATRIAL NATRIURETIC POLYPEPTIDE (ANP): Basic and Clinical Research : 51th Annual Scientific Session of the Japanese Circulation Society
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概要
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The mechanism by which atrial natriuretic peptide (ANP) acts on cells remains obscure. Using cultured vascular smooth muscle cells (VSMC) from rat aorta, we studied the structure-activity relationship of α-human(h) ANP and attempted to clarify its cellular mechanism of action .Binding studies using a variety of synthetic α-hANP^<7-28> analogs with deletion and substitution of amino-acid residue(s) within the ring structure and deamino-dicarba analogs with replacement of the disulfide bond with an ethylene linkage, suggested that the original cyclic structure is a minimum requirement for biological activity and the disulfide bond is not essential for receptor binding. The present study using VSMC loaded with a fluorescent Ca^<2+> indicator quin-2 revealed that α-rat(r) ANP has no effect on increases in cytosolic free Ca^<2+> concentration stimulated by angiotensin (A) II or arginine-vasopression (AVP). While both vasoconstrictive hormones rapidly stimulated phosphatidylinositol (PI) response in VSMC, pretreatment with rANP did not affect AII-or AVP-induced PI response. However, AII-stimulated phosphorylation level of 20 K-dalton (Da) myosin light chain (MLC), a regulatory contractile protein of VSMC, was attenuated by pretreatment with rANP. These data suggest that ANP may not act at site of either agonist-induced membrane PI hydrolysis or intracellular Ca^<2>-signal system, but may partly be involved in phosphorylation/dephosphorylation of 20 K-Da MLC in cultured rat VSMC.
- 社団法人日本循環器学会の論文
- 1988-12-20
著者
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Kawahara Yasuhiro
Department of Internal Medicine (1st Division), Kobe University School of Medicine
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TAKAI Yoshimi
Department of Internal Medicine Biochemistry Kobe University School of Medicine
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Kawahara Yasuhiro
Department Of Biochemistry Kobe University School Of Medicine
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HIRATA YUKIO
Hypertension-Endocrine Division, National Cardiovascular Center Research Institute
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TAKATA SHOICHIRO
Hypertension-Endocrine Division, National Cardiovascular Center Research Institute
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CHINO NAOYOSHI
Peptide Institute Inc., Protein Research Foundation
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KIMURA TERUTOSHI
Peptide Institute Inc., Protein Research Foundation
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SAKAKIBARA SHUMPEI
Peptide Institute Inc., Protein Research Foundation
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Hirata Yukio
Hypertension Division National Cardio-vascurar Center Reseach Institute
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Hirata Yukio
Hypertension-endocrine Division National Cardiovascular Center Research Institute
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Chino Naoyoshi
Peptide Institute Inc. Protein Research Foundation
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Sakakibara Shumpei
Peptide Institute Inc. Protein Research Foundation
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Takata Shoichiro
Hypertension-endocrine Division National Cardiovascular Center Research Institute
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Kimura Terutoshi
Peptide Institute Inc.
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Takai Yoshimi
Department Of Biochemistry Kobe University School Of Medicine
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Sakakibara Shumpei
Peptide Center, Institute for Protein Research, Osaka University
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Kimura Terutoshi
Peptide Center, Institute for Protein Research, Osaka University
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