Conclusion: Taken together, these results indicate that [alpha]-hederin acts as an indirect GRK2 inhibitor leading to a reduced homologous desensitization of [[beta].sub.2]AR-GFP in HEK293 cells
This desensitization is either mediated by phosphorylation of Ser345/346 and Ser261/262 by PKA (heterologous desensitization) or by phosphorylation of certain serines, especially Ser355/356 in the C-terminus of [[beta].sub.2]AR by G-protein coupled receptor kinase 2 (GRK2) (homologous desensitization) (Tran et al., 2004).
The responsiveness of many G protein-coupled receptors (GPCR) and thus also for the [[beta].sub.2]AR is regulated at conditions of high agonist concentrations by heterologous and homologous desensitization and subsequently by internalization.
In homologous desensitization the [[beta].sub.2]AR is phosphorylated at several serines and threonines in the C-terminus by GRKs.
In normal individuals, ghrelin is partially resistant to a previous administration of GHRP-6 and to the ensuing GH rise for which two types of cellular responses have been proposed: the homologous desensitization effects and the cross-talk observed between the GHRH receptor and the GHS receptor.
Ghrelin-induced GH secretion in normal subjects is partially resistant to homologous desensitization by GH-releasing peptide-6.