Short- and long-term regulation of adenylyl cyclase activity by delta-opioid receptor are mediated by Galphai2 in neuroblastoma N2A cells

Molecular Pharmacology
Lei ZhangPing-Yee Law

Abstract

Activation of the opioid receptor results in short-term inhibition of intracellular cAMP levels followed by receptor desensitization and subsequent increase of cAMP above the control level (adenylyl cyclase superactivation). Using adenovirus to deliver pertussis toxin-insensitive mutants of the alpha-subunits of G(i/o) that are expressed in neuroblastoma Neuro2A cells (Galpha(i2), Galpha(i3), and Galpha(o)), we examined the identities of the G proteins involved in the short- and long-term action of the delta-opioid receptor (DOR). Pertussis toxin pretreatment completely abolished the ability of [d-Pen(2), d-Pen(5)]-enkephalin (DPDPE) to inhibit forskolin-stimulated intracellular cAMP production. Expression of the C352L mutant of Galpha(i2), and not the C351L mutants of Galpha(i3) or Galpha(o), rescued the short-term effect of DPDPE after pertussis toxin treatment. The ability of Galpha(i2) in mediating DOR inhibition of adenylyl cyclase activity was also reflected in the ability of Galpha(i2), not Galpha(i3) or Galpha(o), to coimmunoprecipitate with DOR. Coincidently, after long-term DPDPE treatment, pertussis toxin treatment eliminated the antagonist naloxone-induced superactivation of adenylyl cyclase activity. Again, only th...Continue Reading

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Citations

May 21, 2011·Cellular and Molecular Neurobiology·Menghang XiaShail K Sharma
Jul 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hui ZhengPing-Yee Law
Jun 28, 2016·Pharmacological Reviews·Louis GendronGraciela Pineyro
Aug 19, 2017·EMBO Molecular Medicine·Lei ZhangPing-Yee Law
May 23, 2014·The Journal of Biological Chemistry·Achla GuptaLakshmi A Devi
Sep 26, 2013·Molecular Pharmacology·Lei ZhangPing-Yee Law
Mar 15, 2018·Journal of Molecular Endocrinology·Sheng Y AngRoger J Summers

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