AM630 antagonism of cannabinoid-stimulated [35S]GTPγS binding in the mouse brain

  title={AM630 antagonism of cannabinoid-stimulated [35S]GTP$\gamma$S binding in the mouse brain},
  author={Yoshiaki Hosohata and Raymond M. Quock and Keiko Hosohata and Alexandros Makriyannis and Paul F. Consroe and William R. Roeske and Henry I. Yamamura},
  journal={European Journal of Pharmacology},
This research was designed to determine the action of the novel aminoalkylindole AM630 (6-iodo-pravadoline) at the cannabinoid receptor by studying its interaction with the cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-y]-(1-naphthalenyl)methanone mesylate) on guanosine-5'-O-(3-[35S]thio) triphosphate ([35S]GTP gamma S) binding in mouse brain. WIN 55,212-2 stimulated [35S]GTP gamma S binding, while AM630 had no… Expand
Evaluation of cannabinoid receptor agonists and antagonists using the guanosine-5'-O-(3-[35S]thio)-triphosphate binding assay in rat cerebellar membranes.
A more detailed characterization of the cannabinoid-stimulated [35S]GTP gamma S binding assay is reported, comparing the relationship between receptor binding and activation and also examining efficacy differences between compounds. Expand
Characterization of the pharmacology of imidazolidinedione derivatives at cannabinoid CB1 and CB2 receptors.
These derivatives exhibit different activities (neutral antagonism and inverse agonism) in the different models of cannabinoid receptors studied, indicating that they act as cannabinoid CB1 receptor neutral antagonists. Expand
Pharmacological Characterization of a Novel Cannabinoid Ligand, MDA19, for Treatment of Neuropathic Pain
It is found that MDA19 exhibited a distinctive in vitro functional profile at rat CB2 receptors and behaved as a CB1/CB2 agonist in vivo, characteristics of a protean agonist. Expand
Evaluation of the in vivo receptor occupancy for the behavioral effects of cannabinoids using a radiolabeled cannabinoid receptor agonist, R‐[125/131I]AM2233
The goal of the present study was to characterize the in vivo binding of the aminoalkyindole‐based, CB1 receptor agonist, R‐[125/131I]AM2233, and to use this radiotracer to selectively measure the receptor occupancy by the related CB1 receptors agonist WIN55212‐2, to the agonist‐preferring affinity state of the receptor. Expand
The Effect of FMRFamide Analogs on [35S]GTP-γ-S Stimulation in Squid Optic Lobes
Abstract Pharmacological study of Phe-Met-Leu-Phe-amide (FMRFa) receptors is hindered by the lack of selective ligands. The classification of these selective ligands is further hampered by theExpand
Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL‐2H3 mast cells
It is demonstrated that CBD augments β‐hexosaminidase release, a marker of cell activation, from antigen‐stimulated and unstimulated cells via a mechanism, which is not mediated by Gi/Go protein‐coupled receptors but rather is associated with a robust rise in intracellular calcium levels sensitive to clotrimazole and nitrendipine. Expand
Lack of a Significant Effect of Cannabinoids upon the Uptake of 2-Deoxy-D-Glucose by Caco-2 Cells
It is hypothesized that cannabinoids do not interfere with the intestinal GLUT2-mediated apical uptake of glucose from these results, and the effect of cannabinoid receptor agonists and antagonists upon the intestinal absorption of glucose is investigated. Expand
Searching for novel ligands for the cannabinoid and related receptors.
The data provide direct evidence to support the hypothesis that unsaturation in the acyl chain of fatty acid ethanolamides affects the ability of cannabinoid ligands and fatty acid amides for GPRl19 to activate CB 1 and CB2. Expand
CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids.
  • M. Ibrahim, F. Porreca, +8 authors T. Malan
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2005
Test the hypothesis that CB(2) receptor activation stimulates release from keratinocytes of the endogenous opioid beta-endorphin, which then acts at local neuronal mu-opioid receptors to inhibit nociception and indicates anatomical specificity of opioid effects. Expand
Pharmacophores for ligand recognition and activation/inactivation of the cannabinoid receptors.
  • P. Reggio
  • Chemistry, Medicine
  • Current pharmaceutical design
  • 2003
This review focuses first on recent CB1 and CB2 SAR and on the pharmacophores that have been developed for ligand recognition at the CB1 receptor and on challenges for future SAR and pharmacophore development. Expand


Cannabinoid receptor stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate binding in rat brain membranes.
Results demonstrate that [35S]GTP gamma S binding in the presence of excess GDP is an effective measure of cannabinoid receptor coupling to G-proteins in brain membranes. Expand
AM630, a competitive cannabinoid receptor antagonist.
Differences in dissociation constant imply that the mouse vas deferens may contain more than one type of cannabinoid receptor, and that the receptors for which AM630 has the highest affinity may not be CB1 cannabinoid receptors. Expand
In vitro autoradiography of receptor-activated G proteins in rat brain by agonist-stimulated guanylyl 5'-[gamma-[35S]thio]-triphosphate binding.
  • L. Sim, D. Selley, S. Childers
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1995
This technique provides a method of functional neuroanatomy that identifies changes in the activation of G proteins by specific receptors and suggests that variations in coupling efficiency may exist between different receptors in various brain regions. Expand
Further evidence for the presence of cannabinoid CB1 receptors in guinea‐pig small intestine
The results support the hypothesis that guinea‐pig small intestine contains prejunctional cannabinoid CB1 receptors through which cannabinoids act to inhibit electrically‐evoked contractions by reducing release of the contractile transmitter, acetylcholine. Expand
Evidence for the presence of cannabinoid CB1 receptors in mouse urinary bladder
The hypothesis that mouse urinary bladder contains prejunctional CB1 cannabinoid receptors which can mediate inhibition of electrically‐evoked contractions, probably by reducing contractile transmitter release is supported. Expand
SR141716A, a potent and selective antagonist of the brain cannabinoid receptor
SR141716A is the first selective and orally active antagonist of the brain cannabinoid receptor and should prove to be a powerful tool for investigating the in vivo functions of the anandamide/cannabinoid system. Expand
Manual of Pharmacologic Calculations: With Computer Programs
Manual of Pharmacologic Calculations with Computer Programs. By R. J. Tallarida and R. B. Murray. New York, Heidelberg and Berlin, Springer‐Verlag, 1981. ix, 150 p. 24·5 cm. Unpriced.