TY - JOUR
T1 - μ and δ opioid receptors differentially couple to G protein subtypes in membranes of human neuroblastoma SH-SY5Y cells
AU - Laugwitz, Karl Ludwig
AU - Offermanns, Stefan
AU - Spicher, Karsten
AU - Schultz, Günter
N1 - Funding Information:
We thank Dr. K.-D. Hinsch (Justus-Liebig-UniversiGt Giepen, Germany) for providing acommon antiserum (AS 8) and a, c,,mmOn antiserum (AS 6), Dr. F.-J. Klinz (Ruhr-UniversitBt Bochum, Cer-many) for helpful suggestions, Dr. Ian Musgraveforcareful read-ingof the manuscript, and I. Reinsch for cell culturing. work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC Section 1734 solely to indicate fact.
PY - 1993/2
Y1 - 1993/2
N2 - Opioids are regarded to act via receptors interacting with heterotrimeric pertussis toxin (PTX)-sensitive G proteins. In membranes of SH-SY5Y cells, the μ-selective agonist [d-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAGO) and the δ-selective agonist [d-Pen2,Pen5]-enkephalin (DPDPE) stimulated incorporation of the photoreactive GTP analog [α-32P]GTP azidoanilide into proteins comigrating with the α subunits of Gi1, Gi2, Gi3, Go1, and another form of Go, presumably Go2. In membranes of PTX-treated cells, both agonists were ineffective. Subtype-specific immunoprecipitation of G protein α subunits photolabeled in the absence or presence of agonists revealed profound differences between μ and δ opioid receptors in coupling to PTX-sensitive G proteins. Whereas activated ° opioid receptors preferentially coupled to Gi1, activated μ opioid receptors more effectively coupled to Gi3. Additionally, we provide evidence that Go subtypes are also differentially activated by the two receptors. Thus, μ and δ opioid receptors appear to discriminate between PTX-sensitive G proteins and lead to activation of distinct G protein subtypes.
AB - Opioids are regarded to act via receptors interacting with heterotrimeric pertussis toxin (PTX)-sensitive G proteins. In membranes of SH-SY5Y cells, the μ-selective agonist [d-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAGO) and the δ-selective agonist [d-Pen2,Pen5]-enkephalin (DPDPE) stimulated incorporation of the photoreactive GTP analog [α-32P]GTP azidoanilide into proteins comigrating with the α subunits of Gi1, Gi2, Gi3, Go1, and another form of Go, presumably Go2. In membranes of PTX-treated cells, both agonists were ineffective. Subtype-specific immunoprecipitation of G protein α subunits photolabeled in the absence or presence of agonists revealed profound differences between μ and δ opioid receptors in coupling to PTX-sensitive G proteins. Whereas activated ° opioid receptors preferentially coupled to Gi1, activated μ opioid receptors more effectively coupled to Gi3. Additionally, we provide evidence that Go subtypes are also differentially activated by the two receptors. Thus, μ and δ opioid receptors appear to discriminate between PTX-sensitive G proteins and lead to activation of distinct G protein subtypes.
UR - http://www.scopus.com/inward/record.url?scp=0027403710&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(93)90314-H
DO - 10.1016/0896-6273(93)90314-H
M3 - Article
C2 - 8382499
AN - SCOPUS:0027403710
SN - 0896-6273
VL - 10
SP - 233
EP - 242
JO - Neuron
JF - Neuron
IS - 2
ER -