Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand

Inverse, protean, and ligand-selective agonism: matters of receptor conformation.

Concepts regarding the mechanisms by which drugs activate receptors to produce physiological response have progressed beyond considering the receptor as a simple on-off switch. Current evidence suggests that the idea that agonists produce only varying degrees of receptor activation is obsolete and must be reconciled with data to show that agonist efficacy has texture as well as magnitude. Thus,...

Inverse agonism at cannabinoid receptors

There are at least two types of cannabinoid receptor, CB1 and CB2, both G protein coupled. CB1 receptors are expressed predominantly at nerve terminals and mediate inhibition of transmitter release. CB2 receptors are found mainly on immune cells, one of their roles being to modulate cytokine release. Endogenous ligands for these receptors (endocannabinoids) also exist. These discoveries have pr...

Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses by A Synthetic TLR3 Ligand Mitigates

Effects of betahistine at histamine H3 receptors: mixed inverse agonism/agonism in vitro and partial inverse agonism in vivo.

We previously suggested that therapeutic effects of betahistine in vestibular disorders result from its antagonist properties at histamine H(3) receptors (H(3)Rs). However, H(3)Rs exhibit constitutive activity, and most H(3)R antagonists act as inverse agonists. Here, we have investigated the effects of betahistine at recombinant H(3)R isoforms. On inhibition of cAMP formation and [(3)H]arachid...

Priming Hepatitis B Surface (HBsAg)- and Core Antigen (HBcAg)-Specific Immune Responses by Chimeric, HBcAg with a HBsAg ‘a’ Determinant

We developed an immunogen to stimulate multivalent immunity against hepatitis B surface antigen (HBsAg) and hepatitis B core antigens (HBcAg). Immune responses specific for both HBsAg and HBcAg play an important role in controlling the infection. HBsAg-specific antibodies mediate elimination of virions at an early stage of infection and prevent the spread of virus. The immunogen was constructed...