Autoradiographic distribution of mu-, delta- and kappa(1)-opioid stimulated [S-35]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-stimu lated [S-35]guanylyl-5'-O-(gamma-thio)-triphosphate (GTP gamma S-) binding in brain sections to localize neuroanatomically functional coupling of rece ptors to intracellular signal transduction mechanisms. In the present study the selective mu-, delta- and kappa(1)-opioid agonists DAMGO ([D-Ala(2),N- Me-Phe(4),Gly-ol(5)]-enkephalin), DPDPE ([D-Pen(2,5)]-enkephalin) and enado line (Cl-977) were used to stimulate [S-35]GTP gamma S-binding in human bra in sections of frontal cortex and cerebellum. In human frontal cortex mu- a nd delta- opioid stimulated [S-35]GTP gamma S-binding was evenly distribute d throughout the gray matter, while kappa(1)-opioid stimulated [S-35]GTPyS- binding was detected predominantly in lamina V and VI. In the cerebellar co rtex stimulated [S-35]GTP gamma S-binding revealed functional coupling of m u - and kappa(1)-opioid receptors in the molecular layer. (C) 2000 Elsevier Science ireland Ltd. All rights reserved.