Effects of chronic desipramine treatment on alpha2-adrenoceptors and mu-opioid receptors in the guinea pig cortex and hippocampus.
The existence of a close relation between presynaptic inhibitory alpha(2)-adrenoceptor and mu-opioid receptor pathways is well established. Such interplay may occur during chronic conditions that give rise to neuroadaptive changes involving both receptor systems. The aim of this study was to examine the effect of chronic treatment with the tricyclic antidepressant drug, desipramine, on alpha(2)-adrenoceptors and mu-opioid receptors in the guinea pig brain. Guinea pigs were treated with 10 mg/kg desipramine, injected i.p. for 21 days, every 24 h. The levels of expression of alpha(2)-adrenoceptors and mu-opioid receptors, the G protein receptor regulatory kinase, GRK2/3 and signal transduction inhibitory G proteins in synaptosomes of the guinea pig hippocampus and cortex were evaluated by immunoblotting. Quantitative analysis of alpha(2)-adrenoceptor and mu-opioid receptor mRNA levels has been carried out by competitive reverse transcriptase polymerase chain reaction. The expression levels of alpha(2)-adrenoceptors and mu-opioid receptors and the respective mRNAs were found unchanged in the cortex, after chronic desipramine treatment. In these experimental conditions alpha(2)-adrenoceptor and mu-opioid receptor levels decreased, while the relevant transcripts increased, in the hippocampus. GRK2/3 levels remained unchanged and increased, respectively, in the cortex and the hippocampus, after chronic exposure to desipramine. In the same experimental conditions, Galpha(i1), Galpha(i2), Galpha(o) and Galpha(z) levels remained unchanged, while Galpha(i3) levels decreased, in the cortex; whereas, Galpha(i1), Galpha(i2) and Galpha(i3) levels significantly increased, and Galpha(o) and Galpha(z) levels remained unchanged, in the hippocampus. On the whole, the present data suggest that alpha(2)-adrenoceptor and mu-opioid receptor expression and transcription are similarly influenced by chronic treatment with desipramine, in the guinea pig cortex and hippocampus. Furthermore, alterations in the levels of regulatory GRK2/3 and of inhibitory signal transduction G proteins, relevant to activation of both receptor pathways, have been documented. The distinct pattern of adaptations of the different protein studied in response to chronic desipramine treatment in both regions is discussed.
Giaroni
Cristina
C
Clinical and Applied Pharmacology Centre, University of Insubria and University of Pavia, via O. Rossi n. 9, I-21100 Varese, Italy. cristina.giaroni@uninsubria.it
Canciani
Luca
L
Zanetti
Elena
E
Giuliani
Daniela
D
Pisani
Rossana
R
Oldrini
Rita
R
Moro
Elisabetta
E
Trinchera
Marco
M
Crema
Francesca
F
Lecchini
Sergio
S
Frigo
Gianmario
G
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000187:drug effects / Q000378:metabolism; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000187:drug effects / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013574:Synaptosomes / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D044385:GTP-Binding Protein alpha Subunits; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D017450:Receptors, Opioid, mu; D054770:G-Protein-Coupled Receptor Kinase 3; D054769:G-Protein-Coupled Receptor Kinase 2; D003891:Desipramine