Autoradiographic distribution of mu-, delta- and kappa 1-opioid stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate binding in human frontal cortex and cerebellum.
Opioid receptors are known to couple to G-proteins and to inhibit adenylyl cyclase. Receptor activation of G-proteins can be measured by agonist-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate (GTP gamma S-) binding in brain sections to localize neuroanatomically functional coupling of receptors to intracellular signal transduction mechanisms. In the present study the selective mu-, delta- and kappa 1-opioid agonists DAMGO ([D-Ala2,N-Me-Phe4, Gly-ol5]-enkephalin), DPDPE ([D-Pen2,5]-enkephalin) and enadoline (CI-977) were used to stimulate [35S]GTP gamma S-binding in human brain sections of frontal cortex and cerebellum. In human frontal cortex mu- and delta- opioid stimulated [35S]GTP gamma S-binding was evenly distributed throughout the gray matter, while kappa(1)-opioid stimulated [35S]GTP gamma S-binding was detected predominantly in lamina V and VI. In the cerebellar cortex stimulated [35S]GTP gamma S-binding revealed functional coupling of mu- and kappa 1-opioid receptors in the molecular layer.
Platzer
S
S
Max Planck Institute of Psychiatry, Kraepelinstrasse 2, 80804, Munich, Germany. stefan.platzer@stud.tu-muenchen.de
Winkler
A
A
Schadrack
J
J
Dworzak
D
D
Tölle
T R
TR
Zieglgänsberger
W
W
Spanagel
R
R
D001345:Autoradiography; D001572:Benzofurans / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000378:metabolism
D001572:Benzofurans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; C116587:kappa(1) opioid receptor; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020881:Enkephalin, D-Penicillamine (2,5)-; D019204:GTP-Binding Proteins; C067110:enadoline