Opioid and cannabinoid receptor inhibition of adenylyl cyclase in brain
Both opioids and cannabinoids bind to G-protein-coupled receptors to inhibit adenylyl cyclase in neurons. These reactions were assayed in brain membranes, where maximal inhibitory activity occurred in the following regions: mu-opioid inhibition in rat thalamus, delta-opioid inhibition in rat striatu...
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Published in | Annals of the New York Academy of Sciences Vol. 654; p. 33 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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United States
28.06.1992
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Abstract | Both opioids and cannabinoids bind to G-protein-coupled receptors to inhibit adenylyl cyclase in neurons. These reactions were assayed in brain membranes, where maximal inhibitory activity occurred in the following regions: mu-opioid inhibition in rat thalamus, delta-opioid inhibition in rat striatum, kappa-opioid inhibition in guinea pig cerebellum, and cannabinoid inhibition in cerebellum. The inhibition of adenylyl cyclase by both cannabinoid and opioid agonists was typical of G-protein-linked receptors: they required GTP, they were not supported by non-hydrolyzable GTP analogs, and they were abolished (in primary neuronal cell culture) by pertussis toxin treatment. The immediate targets of this system were determined by assaying protein phosphorylation in the presence of receptor agonists and App(NH)p, a substrate for adenylyl cyclase. In striatal membranes, opioid agonists inhibited the phosphorylation of at least two bands of MW 85 and 63 kDa, which may be synapsins I and II, respectively. Other experiments determined the long-term effects of this second messenger system. In primary neuronal cultures, opioid-inhibited adenylyl cyclase attenuated forskolin-stimulated pro-enkephalin mRNA levels, thus providing a feedback regulation of opioid synthesis. Finally, in cerebellar granule cells, both cannabinoid and opioid receptors may exist on the same cells. In these cells, agonists which bind to different receptor types may produce similar biological responses. |
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AbstractList | Both opioids and cannabinoids bind to G-protein-coupled receptors to inhibit adenylyl cyclase in neurons. These reactions were assayed in brain membranes, where maximal inhibitory activity occurred in the following regions: mu-opioid inhibition in rat thalamus, delta-opioid inhibition in rat striatum, kappa-opioid inhibition in guinea pig cerebellum, and cannabinoid inhibition in cerebellum. The inhibition of adenylyl cyclase by both cannabinoid and opioid agonists was typical of G-protein-linked receptors: they required GTP, they were not supported by non-hydrolyzable GTP analogs, and they were abolished (in primary neuronal cell culture) by pertussis toxin treatment. The immediate targets of this system were determined by assaying protein phosphorylation in the presence of receptor agonists and App(NH)p, a substrate for adenylyl cyclase. In striatal membranes, opioid agonists inhibited the phosphorylation of at least two bands of MW 85 and 63 kDa, which may be synapsins I and II, respectively. Other experiments determined the long-term effects of this second messenger system. In primary neuronal cultures, opioid-inhibited adenylyl cyclase attenuated forskolin-stimulated pro-enkephalin mRNA levels, thus providing a feedback regulation of opioid synthesis. Finally, in cerebellar granule cells, both cannabinoid and opioid receptors may exist on the same cells. In these cells, agonists which bind to different receptor types may produce similar biological responses. |
Author | Sexton, T Konkoy, C Pacheco, M Childers, S R Fleming, L Marckel, D Ward, S |
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SubjectTerms | Adenylyl Cyclase Inhibitors Adenylyl Imidodiphosphate - pharmacology Analgesics - pharmacology Animals Brain - drug effects Brain - enzymology Brain - physiology Cannabinoids - metabolism Cannabinoids - pharmacology Cells, Cultured Colforsin - pharmacology Cyclic AMP - metabolism Enkephalin, Ala-MePhe-Gly Enkephalin, Leucine - analogs & derivatives Enkephalin, Leucine - pharmacology Enkephalin, Leucine-2-Alanine - analogs & derivatives Enkephalin, Leucine-2-Alanine - pharmacology Enkephalins - genetics Enkephalins - pharmacology Male Neurons - drug effects Neurons - enzymology Protein Precursors - genetics Rats Rats, Inbred Strains Receptors, Cannabinoid Receptors, Drug - drug effects Receptors, Drug - physiology Receptors, Opioid - drug effects Receptors, Opioid - physiology RNA, Messenger - metabolism |
Title | Opioid and cannabinoid receptor inhibition of adenylyl cyclase in brain |
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