No change in cortical muscarinic M2, M3 receptors or [35S]GTPgammaS binding in schizophrenia.
Muscarinic M1, but not M4, receptors have been shown to be decreased in Brodmann's area (BA) 9 obtained postmortem from subjects with schizophrenia. This study extends that data by measuring levels of muscarinic M2 and M3 receptor protein and mRNAs in BA 9 and BA 40 from the same cohorts of subjects used in the study of M1 and M4 receptors. In addition, the ability of carbachol to stimulate muscarinic receptors that signal through the Gi/o G-proteins was measured in BA 9 from the same cohorts of subjects. There were no changes in levels of muscarinic M2 or M3 protein or M3 mRNA with diagnosis in either CNS region. M2 receptor mRNA could not be detected in BA 9 or BA 40. Finally, carbachol-stimulated GTPgammaS binding did not differ between the diagnostic cohorts in BA 9 (p = 0.64). These data add considerable weight to the argument that the muscarinic M1 receptor is the muscarinic receptor predominantly affected in BA 9 by the pathology of schizophrenia. Given the widespread changes in muscarinic receptors identified in the CNS of subjects of schizophrenia using functional neuroimaging it remains possible that receptors other than the M1 receptor may be altered in different CNS regions.
Scarr
Elizabeth
E
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia.
Keriakous
Dahlia
D
Crossland
Nicola
N
Dean
Brian
B
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001665:Binding Sites; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D011869:Radioligand Assay; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013462:Sulfur Radioisotopes
D014150:Antipsychotic Agents; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D013462:Sulfur Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002217:Carbachol