Abstract
Chronic exposure to opiate agonists (followed by agonist withdrawal) leads to a large increase in the activity of adenylyl cyclase (AC) isozymes I, V, VI, and VIII, a phenomenon defined as AC superactivation (or supersensitization). On the other hand, AC isozymes belonging to the AC-II family (AC-II, AC-IV, and AC-VII) show decreased activity, referred to as superinhibition. Using COS-7 cells transiently transfected with mu-opioid receptor and AC-II, we show here that inhibition of PKC and tyrosine kinase activities synergistically reduced the level of AC-II superinhibition. Moreover, inhibitor of Raf-1 kinase also led to a decrease in AC-II superinhibition. These data suggest that Raf-1, activated by PKC and tyrosine kinase, has a role in the regulation of AC-II superinhibition.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclase Inhibitors*
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Adenylyl Cyclases / genetics
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Adenylyl Cyclases / metabolism
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Analgesics, Opioid / metabolism
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Animals
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COS Cells
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Chlorocebus aethiops
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / metabolism
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Enzyme Inhibitors / metabolism*
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Heterotrimeric GTP-Binding Proteins / metabolism
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Morphine / metabolism
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Okadaic Acid / metabolism
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Phosphorylation
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Protein Kinase C / antagonists & inhibitors
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Protein Subunits / metabolism
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Proto-Oncogene Proteins c-raf / antagonists & inhibitors
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Receptors, Opioid, mu / genetics
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Receptors, Opioid, mu / metabolism
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Receptors, Thyrotropin / genetics
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Receptors, Thyrotropin / metabolism
Substances
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Adenylyl Cyclase Inhibitors
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Analgesics, Opioid
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Enzyme Inhibitors
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Isoenzymes
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Protein Subunits
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Receptors, Opioid, mu
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Receptors, Thyrotropin
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Okadaic Acid
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Morphine
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-raf
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Protein Kinase C
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Heterotrimeric GTP-Binding Proteins
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Adenylyl Cyclases
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adenylyl cyclase 2