Regulation of Guanylate Cyclase by ATP and Dithiothreitol in Rat Lung Membrane : Involvement of an Insensitive and a Sensitive State to ATP/Dithiothreitol-Stimulation
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概要
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ATP/dithiothreitol (DTT)-stimulated guanylate cyclase (GC) in lung membrane was stimulated 18-fold by ATP and DTT, and both its activity and atrial natriuretic peptide (ANP)-stimulated GC activity were observed to be additive. ATP/DTT-stimulated GC was solubilized by octyl glucoside (OG) to examine the mechanism of ATP/DTT-stimulation. GC in OG-extracts was stimulated maximally 2.5-fold by both ATP, ATPγS or AMPPNP, and DTT. preincubation of OG-extracts at 10°C with AMPPNP and DTT (1st-preincubation) converted GC to an insensitive state to stimulation by both ATP and DTT, and this conversion was partly inhibited by a protein phosphatase-1 inhibitor (10 – 1000 nM okadaic acid). On the other hand, ANP-stimulated GC was not converted to an insensitive state to ANP/ATP-stimulation by the 1st-preincubation. Subsequent preincubation of OG-extracts at 10°C with both DTT and, ATP or ATPγS but not AMPPNP converted GC to a state sensitive to ATP/DTT-stimulation, and this conversion was partly inhibited by inhibitors of Ca2+/calmodulin-dependent protein kinase II (KN-62 and KN-93). In contrast, the preincubation with KN-62 and KN-93 had no effect on ANP-stimulated GC activity. The results suggested that phosphorylation was involved in the regulation of ATP/DTT-stimulated GC sensitivity to ATP/DTT-stimulation and that ATP/DTT-stimulated GC activity was likely to be a different type from ANP-stimulated GC activity.
- 社団法人 日本薬理学会の論文
- 2002-05-01
著者
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Asakawa T
Department Of Pharmacology Faculty Of Medicine Saga Medical School
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Asakawa Takeo
Department Of Pharmacology Saga Medical School
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Takano Masako
Department Of Pharmacology Faculty Of Medicine Saga Medical School
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LUO Shiwen
Department of Pharmacology, Faculty of Medicine, Saga Medical School
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Luo Shiwen
Department Of Pharmacology Faculty Of Medicine Saga Medical School
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ASAKAWA Takeo
Department of Pharmacology I, Osaka University School of Medicine
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