Modulation of Ca2+/calmodulin-dependent protein kinase II activity by acute and chronic morphine administration in rat hippocampus: differential regulation of alpha and beta isoforms.
Calcium/calmodulin-dependent protein kinase II (CaMK II) has been shown to be involved in the regulation of opioid receptor signaling. The present study showed that acute morphine treatment significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus, with little alteration in the protein level of either alpha or beta isoform of CaMK II. However, chronic morphine treatment, by which rats were observed to develop apparent tolerance to morphine, significantly down-regulated both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II and differentially regulated the expression of alpha and beta isoforms of CaMK II at protein and mRNA levels. Application of naloxone or discontinuation of morphine treatment after chronic morphine administration, which induced the withdrawal syndrome of morphine, resulted in the overshoot of CaMK II (at both protein and mRNA levels) and its kinase activity. The phenomena of overshoot were mainly observed in the beta isoform of CaMK II but not in the alpha isoform. The effects of both acute and chronic morphine treatments on CaMK II could be completely abolished by the concomitant application of naloxone, indicating that the effects of morphine were achieved through activation of opioid receptors. Our data demonstrated that both acute and chronic morphine treatments could effectively modulate the activity and the expression of CaMK II in the hippocampus.
Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai, People's Republic of China.
L
L
Lou
T
T
Zhou
P
P
Wang
G
G
Pei
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D009270:Naloxone; D009020:Morphine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases