Dopamine D1, D2 and mu-opioid receptors are co-expressed with adenylyl cyclase 5 and phosphodiesterase 7B mRNAs in striatal rat cells.
Intracellular cAMP levels are regulated by cAMP synthesis and degradation rate. Nine isoforms of cAMP-synthesizing enzymes called adenylyl-cyclases (ACs) and eleven phosphodiesterases (PDEs) that degrade cyclic nucleotides have been identified. Both types of enzymes exhibit variations not only in their expression pattern distribution throughout the brain, but also in their regulatory characteristics. Different isoforms of ACs and PDEs may be co-expressed in a single cell, thus a gradient of cAMP intracellular levels is formed, which accounts for the diversity of cell responses. Among these isoforms, AC5 and PDE7B are highly expressed in striatum, where the cAMP pathway is implicated in diverse behavioural functions. Striatal AC5 is involved in drug reinforcing actions and motor activity. Less is known about the role of the PDE7B isoenzyme. We performed a double in situ hybridization analysis of the co-expression patterns of AC5 and PDE7B with mu-opioid-receptor (MOR), D1- and D2-receptor mRNAs to contribute to a better understanding in the regulation of cAMP levels under dopamine or opioidergic pathway activation in striatum. We found co-expression of AC5 and PDE7B mRNAs in caudate-putamen and nucleus accumbens; we also encountered that more than 50% of MOR, D2- and D1-expressing cells contained AC5 and PDE7B mRNAs. The presence of AC5 and PDE7B mRNAs in D1- and D2-containing cells suggests the participation of these enzymes in striatal functions involving dopaminergic pathways. Co-localization of both isoenzyme mRNAs with MOR expressing cells suggests their involvement in opioid reinforcing effects.
de Gortari
Patricia
P
Department of Neurochemistry and Neuropharmachology, Institut d'Investigacions, Biomèdiques de Barcelona, CSIC-IDIBAPS, CIBERNED, c/Rosselló 161, 6a, E-08036 Barcelona, Spain.
Mengod
Guadalupe
G
D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology*; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517467:Pde7b protein, rat; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6