Decrease of adenylyl cyclase activity and expression by a sigma1 receptor ligand and putative atypical antipsychotic.
We examined whether changes in the adenylyl cyclase system could be induced by the administration of the sigma1 receptor ligand and putative atypical antipsychotic 4-[4-fluorophenyl]-1,2,3,6-tetrahydro-1-[4-[1,-2,4-triazol-1-il]butyl]pyridine citrate) (E-5842). Repeated (21 days) but not acute (2 h) treatment with E-5842 induced a significant decrease in adenylyl cyclase type I immunoreactivity and adenylyl cyclase activity in rat frontal cortex membranes, with less or no effect in other brain regions such as the hippocampus or the striatum. Changes in immunoreactivity were not observed in other adenylyl cyclases (type V/VI). The reported changes, observed only after a chronic treatment, could be related to the mechanism of action of sigma receptor ligands in general or to that of E-5842 in particular and should be taken into account, given the long duration of treatment in psychiatric patients.
Monroy
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X
Department of Neuropharmacology, Research Center, Laboratoris Esteve, S.A., Verge de Montserrat 221, 08041-Barcelona, Spain.
Romero
G
G
Pérez
M P
MP
Farré
A J
AJ
Guitart
X
X
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008024:Ligands; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D014230:Triazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; C117757:E 5842; D008024:Ligands; D011725:Pyridines; D017480:Receptors, sigma; D014230:Triazoles; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases