Disease relevance of PTHR2

• In patients with hyperparathyroidism the PTH2 receptor is down-regulated as function of plasma PTH levels [1].

High impact information on PTHR2

• Tuberoinfundibular peptide of 39 residues (TIP39) was recently purified from bovine hypothalamus based on selective PTH2 receptor activation [2].
• TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus [3].
• The structural features of TIP39, determined in the presence of a zwitterionic lipid to mimic the membrane environment of the G-protein-coupled PTH2 receptor, consist of two alpha-helices, Ala(5)-Arg(21) and Leu(26)-Val(35) [4].
• Genomic and cDNA clones encoding portions of a putative catfish parathyroid hormone (PTH) 2 receptor (PTH2R) led to the isolation of a cDNA encoding a full-length zebrafish PTH2R (zPTH2R) [5].
• Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-2 receptor agonist [6].

Biological context of PTHR2

• The PTH2 receptor is much more selective in ligand recognition and appears to have a more specific tissue distribution [7].
• Candidate gene analysis suggested a possible association of a PTHR2 variant with generalized radiographic OA; it is, however, unlikely the major disease gene for the observed linkage to the FOA phenotype.European Journal of Human Genetics (2006) 14, 1280-1287. doi:10.1038/sj.ejhg.5201704; published online 16 August 2006 [8].
• Recently, a homologous receptor, the PTH-2 receptor, was obtained from rat and human brain cDNA libraries [6].
• The human PTH2 receptor: binding and signal transduction properties of the stably expressed recombinant receptor [9].
• Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization [10].

Anatomical context of PTHR2

• RESULTS: Mean relative antigen density of the PTH2 receptor and percentage of positive cells in healthy subjects was 19 +/- 5 and 90 +/- 6% on granulocytes, 5 +/- 2 and 55 +/- 19% on monocytes, and 24 +/- 7 and 21 +/- 7% on lymphocytes [1].
• CONCLUSIONS: The PTH2 receptor is expressed on human granulocytes and--to a lesser degree--on monocytes and lymphocytes [1].
• METHODS: PTH2 receptor expression was quantified by flow cytometry (FACS) analysis on monocytes, lymphocytes and granulocytes that were isolated from peripheral blood (hypotonic density gradient centrifugation) and by immunohistochemistry using a specific alpha-PTH2-R antibody produced in rabbit [1].
• We therefore investigated the expression of the PTH2 receptor on human leukocytes in healthy subjects and in patients with hyperparathyroidism [1].
• Labeling with the antibody identified a number of endocrine cells expressing the PTH2 receptor, including thyroid parafollicular cells, pancreatic islet D cells, and some gastrointestinal peptide synthesizing cells [11].

Physical interactions of PTHR2

• This method is useful for measurement of agonist and antagonist radioligand binding at the PTH-1 receptor and binding of [125I]PTH(1-34) at the PTH-2 receptor [12].

Regulatory relationships of PTHR2

• The PTH2 receptor is activated by TIP39 but not by PTHrP [13].

Other interactions of PTHR2

• Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor [7].
• Recently, a new G protein-coupled receptor with substantial implications for vascular function--the PTH2 receptor (PTH2-R)--has been identified, however, expression and distribution in humans and a possible regulation has not yet been studied [1].
• In fact there is more than one receptor - the PTH2 receptor and a putative carboxy-terminal PTH receptor [14].
• In particular, the [Bpa2]- and [Bpa4]-substituted analogs selectively antagonized and preferentially cross-linked to the PTH-1 receptor and PTH-2 receptor, respectively [15].

Analytical, diagnostic and therapeutic context of PTHR2

• In the present study, we investigated the expression of TIP39 and the PTH2 receptor in male and female rat brain during postnatal development by means of in situ hybridization histochemistry, quantitative RT-PCR, and immunocytochemistry [16].

References