Sensitization of the Adenylyl Cyclase System in Cloned k-Opioid Receptor-Transfected Cells Following Sustained Agonist Treatment. A Chimeric Study Using G Protein .ALPHA.i2/.ALPHA.q Subunits.
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- Nakagawa Takayuki
- Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University
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- Ozawa Tohru
- Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University
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- Watanabe Takeshi
- Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University
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- Minami Masabumi
- Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University
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- Satoh Masamichi
- Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University
Bibliographic Information
- Other Title
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- Sensitization of the Adenylyl Cyclase System in Cloned κ-Opioid Receptor-Transfected Cells Following Sustained Agonist Treatment:A Chimeric Study Using G Protein αi2/αq Subunits
- Sensitization of the Adenylyl Cyclase System in Cloned カッパーOpioid Receptor-Transfected Cells Following Sustained Agonist Treatment A Chimeric Study Using G Protein アルファ i2 アルファ q Subunits
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Abstract
Chronic and/or sustained opioid treatment has been shown to result in development of sensitization of the adenylyl cyclase (AC) system or cAMP overshoot. In this study, we investigated the molecular mechanism responsible for sensitization of the AC system using CHO cells co-expressing cloned κ-opioid receptor and some chimeric G protein αi2/αq subunits. In CHO cells co-expressing the κ-opioid receptor and pertussis toxin-insensitive chimeric αi2/αq subunits with αi2 residues Met244 - Asn331, despite pretreatment with pertussis toxin, acute treatment with the κ-opioid-receptor - selective agonist U69, 593 suppressed forskolin-stimulated cAMP accumulation, while sustained treatment with U69, 593 (4 h) induced cAMP overshoot over the naive level by the κ-opioid-receptor - selective antagonist norbinaltorphimine (sensitization of the AC system). On the other hand, in CHO cells co-expressing the κ-opioid receptor and pertussis toxin-insensitive chimeric αi2/αq subunits without αi2 residues Met244 - Asn331, pretreatment with pertussis toxin completely blocked these acute and sustained effects of U69, 593 on cAMP accumulation. These results suggested that the presence of the specific region of αi2 (Met244 - Asn331), which was reported to be responsible for the inhibition of AC, and continuous inhibition of AC by αi2 is necessary for the development of sensitization.
Journal
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- The Japanese Journal of Pharmacology
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The Japanese Journal of Pharmacology 81 (4), 353-361, 1999
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390282679261389312
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- NII Article ID
- 10008197587
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- NII Book ID
- AA00691188
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- COI
- 1:CAS:528:DC%2BD3cXhtFGrtQ%3D%3D
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- ISSN
- 13473506
- 00215198
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- NDL BIB ID
- 4948536
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- PubMed
- 10669040
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed