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 μ-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.
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Schallmach, E., Steiner, D. & Vogel, Z. Inhibition of AC-II activity following chronic agonist exposure is modulated by phosphorylation. J Mol Neurosci 29, 115–122 (2006). https://doi.org/10.1385/JMN:29:2:115
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DOI: https://doi.org/10.1385/JMN:29:2:115