Toward Defining the Pharmacophore for Positive Allosteric Modulation of PTH1 Receptor Signaling by Extracellular Nucleotides.

ABSTRACT: The parathyroid hormone 1 receptor (PTH1R) is a Class B G-protein-coupled receptor that is a target for osteoporosis therapeutics. Activated PTH1R couples through Gs to the stimulation of adenylyl cyclase. As well, β-arrestin is recruited to PTH1R leading to receptor internalization and MAPK/ERK signaling. Previously, we reported that the agonist potency of PTH1R is increased in the presence of extracellular ATP, which acts as a positive allosteric modulator of PTH signaling. Another nucleotide, cytidine 5'-monophosphate (CMP), also enhances PTH1R signaling, suggesting that ATP and CMP share a moiety responsible for positive allostery, possibly ribose-5-phosphate. Therefore, we examined the effect of extracellular sugar phosphates on PTH1R signaling. cAMP levels and β-arrestin recruitment

SUBMITTER: Kim BH 

PROVIDER: S-EPMC7088899 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature