Colocalization of mu-opioid receptors and activated G-proteins in rat cingulate cortex.
Anterior cingulate cortex (ACC) has a role in pain processing, however, little is known about opioid system organization and actions. This rodent study defines opioid architecture in the perigenual and midcingulate divisions of ACC, relates mu-opioid receptor binding and G-protein activation, and localizes such binding to afferent axons with knife-cut lesions and specifically to noradrenergic terminals with immunotoxin lesions (anti-dopamine beta-hydroxylase-saporin; anti-DBH-saporin). [(3)H]Tyr-D-AlaGly-MePhe-Gly-ol (DAMGO) binding was highest in perigenual areas 32 and 24 with a peak in layer I. Midcingulate area 24' and posterior cingulate area 29 had overall lower binding in each layer. In contrast, DAMGO-stimulated [(35)S]guanosine-5'-O-(gamma-thio)-triphosphate (GTPgammaS) binding in area 24' was similar to that in area 24, whereas area 29 had low and homogeneous binding. Undercut lesions reduced [(3)H]DAMGO binding in all layers with the greatest loss in layer I (-65%), whereas DAMGO-stimulated [(35)S]GTPgammaS binding losses occurred in only layers I-III. Anti-DBH-saporin reduced [(3)H]DAMGO binding in layer I of area 24; DAMGO-stimulated [(35)S]GTPgammaS binding was unchanged in areas 24' and 29. Correlation analysis of receptor and G-protein activation before and after undercut lesions suggested there were a greater number of DAMGO receptor sites for each G-protein on axons, than on somata and proximal dendrites. Finally, perigenual and midcingulate cortices have different opioid architectures due to a higher proportion of mu-opioid receptors expressed by afferent axons in areas 24 and 32.
Vogt
L J
LJ
Cingulum NeuroSciences Institute, Syracuse, New York, USA. lvogt@cingulumneurosciences.org
Sim-Selley
L J
LJ
Childers
S R
SR
Wiley
R G
RG
Vogt
B A
BA
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D002540:Cerebral Cortex / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism*; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013223:Statistics as Topic; D013462:Sulfur Radioisotopes; D014316:Tritium
D000701:Analgesics, Opioid; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D017450:Receptors, Opioid, mu; D054789:Ribosome Inactivating Proteins, Type 1; D013462:Sulfur Radioisotopes; C101397:anti-dopamine beta-hydroxylase immunotoxin; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000076985:Saporins; D019204:GTP-Binding Proteins