Endocrine Abstracts

The octapeptide hormone angiotensin II (Ang II) exerts its major biological effects via angiotensin AT1 receptors (AT1Rs). Signaling of AT1Rs is regulated by ß-arrestins, which bind to activated AT1Rs, uncouple them form G proteins, and initiate their internalization via clathrin-coated pits and cause G protein independent MAP kinase activation. It has been shown previously that AT1Rs internalize via ß-arrestin-d...

The majority of loss-of function mutations of G protein coupled receptors, leading to diseases, such as diabetes insipidus (V2 vasopressin receptor) or retinitis pigmentosa (rhodopsin) are consecutive to retention of the receptor in the endoplasmic reticulum (ER). Cell surface expression and biological function can be restored by membrane-permeable ligands called pharmacological chaperones. The V1b/V3R, one of the 3 subtypes of vasopressin receptors, is involved in the regulat...

For over two decades the hypothesis of dimerization of G protein coupled receptors (GPCR) exist. But only in 1999 it became clear by investigation of GABA B receptors that dimerization is the prerequisite for function. Since then our understanding of GPCR function is widened by the fact that nearly all GPCRs form dimers or higher order oligomers. This formation of GPCR homodimers or heterodimers influence the functional properties of a GPCR from that we know of a monomer in it...

Conventionally, an allosteric modulator is neutral in respect of efficacy and binds to a receptor site distant from the orthosteric site of the endogenous agonist. However, recently compounds being ago-allosteric modulators have been described i.e. compounds acting both as agonists on their own and as enhancers for the endogenous agonists in both increasing agonist potency and often providing additive efficacy - superagonism. The additive efficacy can also be observed with ago...