Abstract
It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o- coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute Mu-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of Gbetagamma subunits (Gbetagamma scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that Gbetagamma is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenylyl Cyclase Inhibitors
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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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Calcium / metabolism*
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Chlorocebus aethiops
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Colforsin / metabolism
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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GTP-Binding Protein beta Subunits / metabolism*
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GTP-Binding Protein gamma Subunits / metabolism*
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Ionomycin / metabolism
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Ionophores / metabolism
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism*
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Morphine / metabolism
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Pertussis Toxin / metabolism
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Phosphodiesterase Inhibitors / metabolism
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Rats
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Receptors, Opioid, mu / metabolism*
Substances
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Adenylyl Cyclase Inhibitors
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Analgesics, Opioid
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Ionophores
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Isoenzymes
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Phosphodiesterase Inhibitors
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Receptors, Opioid, mu
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Colforsin
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Ionomycin
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Morphine
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Pertussis Toxin
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GTP-Binding Protein alpha Subunits, Gi-Go
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Adenylyl Cyclases
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Calcium