Characterization Of Pth Type-2 Receptor (pth2rb) And Its Endogenous Ligand Pth2 In Zebrafish Development

Members of the parathyroid hormone family of ligands, PTH (parathyroid hormone), PTH2, and PTHLH (parathyroid hormone-like hormone). These hormones interact with the class B GCPRs parathyroid hormone receptors PTH1R, PTH2R, and PTH3R to regulate a variety of biological processes. In mammals, PTH and PTHLH activate PTH1R and PTH3R to mediate serum calcium homeostasis, chondrogenesis, and bone maintenance. PTH2R activation by PTH2 has been studied primarily in regard to its neuroendocrine roles but is also found in the skin where it contributes to wound healing and keratinocyte differentiation. Still, little is known about the impacts of PTH2R signaling relative to PTH1R and PTH3R. Here, we identify and characterize a paralog of the zebrafish pth2r gene we call pth2rb. Expression studies reveal that pth2rb is detectable in the developing zebrafish forebrain-midbrain in close proximity to PTH2. Functional investigation of Pth2rb stimulation by PTH2 shows a greater maximum response in intracellular cAMP compared to that of zebrafish Pth2ra. Together these studies provide the initial groundwork for further evaluations of the PTH2/PTH2R signaling interactions that may be applicable across species