+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Chronic morphine augments adenylyl cyclase phosphorylation: relevance to altered signaling during tolerance/dependence



Chronic morphine augments adenylyl cyclase phosphorylation: relevance to altered signaling during tolerance/dependence



Molecular Pharmacology 54(6): 949-953



Despite the demonstration that chronic morphine increases phosphorylation of multiple substrate proteins, their identity has, for the most part, remained elusive. Thus far, chronic morphine has not been shown to increase the phosphorylation of any identified effector protein. This is the first demonstration that persistent activation of opioid receptors has profound effects on phosphorylation of adenylyl cyclase (AC). A dramatic increase in phosphorylation of AC (type II family) was observed in ileum longitudinal muscle myenteric plexus preparations obtained from chronic morphine-treated guinea pigs. Analogous results were obtained when AC was immunoprecipitated using two differentially directed AC antibodies. The magnitude of the augmented AC phosphorylation was substantially attenuated by chelerythrine, a protein kinase C-selective inhibitor. These results suggest the potential relevance of increased phosphorylation (protein kinase C-mediated) of AC to opioid tolerant/dependent mechanisms. Because phosphorylation of AC isoforms (type II family) can significantly increase their stimulatory responsiveness to Gbetaalpha and Gbetagamma, this mechanism could underlie, in part, the predominance of opioid AC stimulatory signaling observed in opioid tolerant/dependent tissue. Moreover, in light of the fact that many G protein-coupled receptors signal through common effector proteins, this effect provides a mechanism for divergent consequences of chronic morphine treatment and could explain the well documented complexity of changes that accompany the opioid tolerant/dependent state.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010322120

Download citation: RISBibTeXText

PMID: 9855621

DOI: 10.1124/mol.54.6.949


Related references

Chronic morphine application increases c-fos expression in mesolimbic structures in rats. Naunyn-Schmiedeberg's Archives of Pharmacology 354(4 Suppl. 1): R45, 1996

Differential effect of chronic ethanol treatment on barbiturate and steroid modulation of muscimol-binding to rat brain cortex. Neuroscience Letters. 158(1): 83-86, 1993

Chronic monocytic leukemia in childhood. Journal of Pediatrics 53(3): 259-270, 1958

Chronic opioid therapy in long-term cancer survivors. Clinical and Translational Oncology 19(2): 236-250, 2017

Ethanol and mk 801 induced locomotor activity are differentially regulated by dopaminergic and serotonergic antagonists in inbred long sleep and short sleep mice. Society for Neuroscience Abstract Viewer and Itinerary Planner : Abstract No 879 17, 2002

Antiarrhythmic effect of lithium in rats after myocardial infarction by activation of Nrf2/HO-1 signaling. Free Radical Biology and Medicine 77: 71-81, 2014

Phosphorylation of Gata1 at serine residues 72, 142, and 3 10 is not essential for hematopoiesis in vivo. Blood 107(9): 3527-3530, 2006

Chronic morphine increases GABA tone on serotonergic neurons of the dorsal raphe nucleus Association with an up-regulation of the cyclic AMP pathway. Neuroscience. 95(2): 433-443,. 1, 2000

Enhanced detection rate of small mutations of the dystrophin gene precludes necessity for muscle biopsy in most Duchenne muscular dystrophy patients. Neurology 56(8 Suppl. 3): A79, 2001

Altered myelopoiesis and the development of acute myeloid leukemia in transgenic mice overexpressing cyclin A1. Proceedings of the National Academy of Sciences of the United States of America 98(12): 6853-6858, 2001

Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proceedings Of The National Academy Of Sciences Of The United States Of America. 92(15): 7105-7109, 1995

Hypersensitivity to nonsteroidal antiinflammatory drugs: indications and methods for oral challenges. Journal of Allergy and Clinical Immunology 64(6 Pt 2): 669-674, 1979

Effects of chronic morphine administration on the reproductive system of the male rat. Journal of Pharmacology and Experimental Therapeutics 192(3): 542-548, 1975