Evidence for GPR107 as a cognate receptor for neuronostatin

Abstract

Neuronostatin is a recently described peptide hormone that is derived from the somatostatin preprohormone. We previously have shown that neuronostatin administered into the lateral cerebroventricle of adult, male rats led to a significant increase in mean arterial pressure (MAP). We sought to determine if this effect of neuronostatin was physiologically relevant; however, any attempt to disrupt the production of neuronosatin would compromise somatostatin as well. We therefore decided to assess instead the effect of loss of the neuronostatin receptor on cardiovascular function. To identify the receptor, we first screened four neuronostatin‐responsive cell types for the expression of orphan GPCRs, and found that GPR107 was present in all cell types tested. We next knocked down the expression of GPR107 in vitro using siRNA, and found that loss of GPR107 abolished neuronostatin‐induced cFos expression. Loss of endogenous GPR107 in male rats ablated the elevation in MAP caused by neuronostatin treatment, and blunted the cardiovascular responses of animals in a baroreceptor sensitivity test. These data suggest that GPR107 is a cognate receptor for neuronostatin, and that this hormone and its receptor are physiologically relevant regulators of cardiovascular function. Supported by NIH#HL66023.