Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase: role of Gbetagamma dimers.
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.
Steiner
Debora
D
Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Avidor-Reiss
Tomer
T
Schallmach
Ester
E
Saya
Daniella
D
Vogel
Zvi
Z
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005576:Colforsin / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D015759:Ionomycin / Q000378:metabolism; D007476:Ionophores / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009020:Morphine / Q000378:metabolism; D037342:Pertussis Toxin / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D051381:Rats; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D000701:Analgesics, Opioid; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D007476:Ionophores; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D017450:Receptors, Opioid, mu; D005576:Colforsin; D015759:Ionomycin; D009020:Morphine; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases; D002118:Calcium