BETA-ADRENERGIC-RECEPTOR KINASE-LIKE ACTIVITY AND BETA-ARRESTIN ARE EXPRESSED IN OSTEOBLASTIC CELLS

Biologic responses to peptide calciotropic hormones, such as parathyro id hormone (PTH) and calcitonin, exhibit desensitization, As with most hormones, however, the mechanisms of desensitization are not complete ly understood; For the beta(2)-adrenergic receptor (beta(2)AR) system, which is coupled to adenylyl cyclase via the stimulatory guanine nucl eotide-binding regulatory (G(s)) protein, homologous desensitization i s mediated in part by a receptor-specific kinase (beta ARK) and a solu ble cofactor (beta-arrestin). Recently, this system has been reported to be involved in rapid homologous desensitization of the PTH/parathyr oid hormone receptor protein (PTHrP) receptor, We have identified the presence of this system in bone using reverse-transcriptase PCR Nucleo tide sequence of PCR fragments from ROS 17/2.8 cells revealed 100% ide ntity with rat brain beta ARK1 and beta-arrestin I sequences, Northern analyses with RNA from ROS 17/2.8,UMR 106-H5 cells, and primary cultu res of nontransformed neonatal rat calvariae demonstrated two mRNA spe cies of 4 and 2.6 kilobases (kb) for beta ARK and 7.5 kb for beta-arre stin, comparable to those found in bovine brain, beta ARK-like activit y was demonstrated in cytosolic extracts of the UMR 106-H5 cells by as sessing phosphorylation of the retinal photoreceptor, rhodopsin, by th e extracts, Phosphorylation was enhanced with light-activated rhodopsi n and by bovine brain G(beta gamma) subunits; heparin inhibited phosph orylation, These findings are characteristic of beta ARK. Expression o f beta-arrestin in the UMR 106-H5 cells was confirmed by immunoblot, T hus, osteoblastic tells express proteins, beta ARK and beta-arrestin, which may regulate desensitization of calciotropic hormone receptors.