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Cannabinoid receptor agonist efficacy for stimulating [35S]GTPgammaS binding to rat cerebellar membranes correlates with agonist-induced decreases in GDP affinity.
J Biol Chem. 1998 Jul 03; 273(27):16865-73.JB

Abstract

The relationship between GDP and cannabinoid-stimulated [35S]guanosine-5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding was investigated in rat cerebellar membranes. Kinetic analyses showed that [35S]GTPgammaS binding reached steady-state levels and that the association rate was increased by the agonist WIN 55212-2 proportional to the concentration of GDP. Dissociation of [35S]GTPgammaS occurred with two rates (t1/2 = 7 and 170 min), and WIN 55212-2 increased the proportion of sites exhibiting the faster rate. Without GDP, [35S]GTPgammaS bound to membranes with high and low affinity, and WIN 55212-2 had no effect. With 30 microM GDP, [35S]GTPgammaS bound to low and intermediate affinity sites, and WIN 55212-2 induced high affinity [35S]GTPgammaS binding without affecting low affinity sites. GDP competed for high affinity [35S]GTPgammaS binding with high and intermediate affinity in the absence of WIN 55212-2 and with high and low affinity in the presence of WIN 55212-2. Cannabinoid ligands displayed differential abilities to maximally stimulate [35S]GTPgammaS binding in the presence of GDP. Efficacy differences among ligands increased with increasing GDP concentrations. GDP competition curves revealed that agonists induced low affinity GDP Ki values that were proportional to agonist Emax values, indicating that agonist efficacy is determined by displacement of GDP from G-proteins.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Center for the Neurobiological Investigation of Drug Abuse, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9642247

Citation

Breivogel, C S., et al. "Cannabinoid Receptor Agonist Efficacy for Stimulating [35S]GTPgammaS Binding to Rat Cerebellar Membranes Correlates With Agonist-induced Decreases in GDP Affinity." The Journal of Biological Chemistry, vol. 273, no. 27, 1998, pp. 16865-73.
Breivogel CS, Selley DE, Childers SR. Cannabinoid receptor agonist efficacy for stimulating [35S]GTPgammaS binding to rat cerebellar membranes correlates with agonist-induced decreases in GDP affinity. J Biol Chem. 1998;273(27):16865-73.
Breivogel, C. S., Selley, D. E., & Childers, S. R. (1998). Cannabinoid receptor agonist efficacy for stimulating [35S]GTPgammaS binding to rat cerebellar membranes correlates with agonist-induced decreases in GDP affinity. The Journal of Biological Chemistry, 273(27), 16865-73.
Breivogel CS, Selley DE, Childers SR. Cannabinoid Receptor Agonist Efficacy for Stimulating [35S]GTPgammaS Binding to Rat Cerebellar Membranes Correlates With Agonist-induced Decreases in GDP Affinity. J Biol Chem. 1998 Jul 3;273(27):16865-73. PubMed PMID: 9642247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor agonist efficacy for stimulating [35S]GTPgammaS binding to rat cerebellar membranes correlates with agonist-induced decreases in GDP affinity. AU - Breivogel,C S, AU - Selley,D E, AU - Childers,S R, PY - 1998/6/27/pubmed PY - 1998/6/27/medline PY - 1998/6/27/entrez SP - 16865 EP - 73 JF - The Journal of biological chemistry JO - J Biol Chem VL - 273 IS - 27 N2 - The relationship between GDP and cannabinoid-stimulated [35S]guanosine-5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding was investigated in rat cerebellar membranes. Kinetic analyses showed that [35S]GTPgammaS binding reached steady-state levels and that the association rate was increased by the agonist WIN 55212-2 proportional to the concentration of GDP. Dissociation of [35S]GTPgammaS occurred with two rates (t1/2 = 7 and 170 min), and WIN 55212-2 increased the proportion of sites exhibiting the faster rate. Without GDP, [35S]GTPgammaS bound to membranes with high and low affinity, and WIN 55212-2 had no effect. With 30 microM GDP, [35S]GTPgammaS bound to low and intermediate affinity sites, and WIN 55212-2 induced high affinity [35S]GTPgammaS binding without affecting low affinity sites. GDP competed for high affinity [35S]GTPgammaS binding with high and intermediate affinity in the absence of WIN 55212-2 and with high and low affinity in the presence of WIN 55212-2. Cannabinoid ligands displayed differential abilities to maximally stimulate [35S]GTPgammaS binding in the presence of GDP. Efficacy differences among ligands increased with increasing GDP concentrations. GDP competition curves revealed that agonists induced low affinity GDP Ki values that were proportional to agonist Emax values, indicating that agonist efficacy is determined by displacement of GDP from G-proteins. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9642247/Cannabinoid_receptor_agonist_efficacy_for_stimulating_[35S]GTPgammaS_binding_to_rat_cerebellar_membranes_correlates_with_agonist_induced_decreases_in_GDP_affinity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)80621-4 DB - PRIME DP - Unbound Medicine ER -