Antidiabetic Properties of the Histamine H3 Receptor Protean Agonist Proxyfan
نویسندگان
چکیده
منابع مشابه
Antagonist affinity measurements at the Gi-coupled human histamine H3 receptor expressed in CHO cells
BACKGROUND The H3 histamine receptor is a Gi-coupled GPCR that has been proven to exist in different agonist-induced states, including that defined by the protean agonist proxyfan. Several GPCRs are now known to exist in different states. For some of these, antagonist affinity measurement remain constant regardless of the state of the receptor, for others e.g. the beta-adrenoceptors, the antago...
متن کاملBioavailability, antinociceptive and antiinflammatory properties of BP 2-94, a histamine H3 receptor agonist prodrug.
(R)alpha-Methylhistamine [(R)alpha-MeHA], a potent and selective histamine H3 receptor agonist in vitro and in vivo in rodents, was found to display comparatively low plasma level in healthy human volunteers, attributable to an extensive methylation of the drug's imidazole ring by histamine-N-methyltransferase. To limit this inactivation process, BP 2-94, ie., (R)-(-)-2-[[N-[1-(1H-imidazol-4-yl...
متن کاملProtean agonism at histamine H3 receptors in vitro and in vivo.
G protein-coupled receptors (GPCRs) are allosteric proteins that adopt inactive (R) and active (R*) conformations in equilibrium. R* is promoted by agonists or occurs spontaneously, leading to constitutive activity of the receptor. Conversely, inverse agonists promote R and decrease constitutive activity. The existence of another pharmacological entity, referred to as "protean" agonists (after ...
متن کاملNo evidence for functional selectivity of proxyfan at the human histamine H3 receptor coupled to defined Gi/Go protein heterotrimers.
Numerous structurally diverse ligands were developed to target the human histamine H(3) receptor (hH(3)R), a presynaptic G(i)/G(o)-coupled auto- and heteroreceptor. Proxyfan was identified to be functionally selective, with different efficacies toward G(i)/G(o)-dependent hH(3)R signaling pathways. However, the underlying molecular mechanism of functional selectivity of proxyfan is still unclear...
متن کاملIdentification and Characterization of ZEL-H16 as a Novel Agonist of the Histamine H3 Receptor
The histamine H3 receptor (H3R) has been recognized as a promising target for the treatment of various central and peripheral nervous system diseases. In this study, a non-imidazole compound, ZEL-H16, was identified as a novel histamine H3 receptor agonist. ZEL-H16 was found to bind to human H3R with a Ki value of approximately 2.07 nM and 4.36 nM to rat H3R. Further characterization indicated ...
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ژورنال
عنوان ژورنال: Endocrinology
سال: 2011
ISSN: 0013-7227,1945-7170
DOI: 10.1210/en.2010-0757