Protocols and Good Operating Practices in the Study of Cannabinoid Receptors.

With the approach of the 30th year since the pioneering discovery of a cannabinoid receptor in rat brain (Devane et al., 1988), the field of cannabinoid pharmacology and physiology has impacted human physiology at multiple levels. The development of highly specific and potent orthosteric ligands, as well as the blossoming field of allosteric ligand development, has placed the endocannabinoid system in the forefront as a modulator of a multitude of physiologic processes.

N-arachidonoyl glycine, another endogenous agonist of GPR55.

Interest in lipoamino acids as endogenous modulators of G-protein coupled receptors has escalated due to their involvement in a variety of physiologic processes. In particular, a role for these amino acid conjugates has emerged in the endocannabinoid system. The study presented herein investigated the effects of N-arachidonoyl glycine (NAGly) on a candidate endocannabinoid receptor, GPR55.

Design, synthesis and biological evaluation of GPR55 agonists.

GPR55, a G protein-coupled receptor, is an attractive target to alleviate inflammatory and neuropathic pain and treat osteoporosis and cancer. Identifying a potent and selective ligand will aid to further establish the specific physiological roles and pharmacology of the receptor. Towards this goal, a targeted library of 22 compounds was synthesized in a modular fashion to obtain structure-activity relationship information.

HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens.

Background: HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc.

Methods: We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc.

Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones.

A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. The design of analogues was guided by the docking of potential compounds into a model of the inactive form of GPR55.