Neuronostatin, derived from the somatostatin preprohormone, is a recently described peptide that is produced by several tissues involved in cardiovascular regulation and metabolism, including the hypothalamus. Injection of neuronostatin into the lateral cerebroventricle led to a dose-related increase in mean arterial pressure (MAP) in rats. Any attempt to inhibit the production of neuronostatin would alter somatostatin production as well, making determination of the physiological relevance of the peptide's pharmacologic effects by compromise of production approaches impossible. Therefore, we employed an alternative approach to identify and compromise the production of the neuronostatin receptor. Because neuronostatin was shown to signal via a PKA-dependent mechanism, we hypothesized that the neuronostatin receptor was a G protein-coupled receptor (GPCR), in particular, one of the orphan GPCRs for which the ligand is unknown. Therefore, we screened neuronostatin-responsive tissues, including hypothalamus, heart, pancreatic α-cells, and the gastric tumor cell line KATOIII, for expression of orphan GPCRs. Four orphan GPCRs were expressed by all cell types, including GPR56 and GPR107. Knockdown of GPR107, but not GPR56 or GPR146, led to a loss of responsiveness to neuronostatin by KATOIII cells. Rats injected with siRNA directed against GPR107 (2 μg/day for 2 days) into the lateral cerebroventricle did not exhibit an increase in MAP in response to neuronostatin treatment. Rats with compromised GPR107 expression also displayed blunted reactivity in a baroreflex sensitivity test, indicating that GPR107 and neuronostatin may be important regulators of cardiovascular function. Thus, GPR107 is a promising candidate receptor for neuronostatin, and neuronostatin, interacting with GPR107, may play an important role in the central control of cardiovascular function.
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http://dx.doi.org/10.1152/ajpregu.00336.2012 | DOI Listing |
Neuropharmacology
November 2024
College of Life Sciences, Northwest Normal University, Lanzhou, Gansu, 730070, China.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, which is characterized by the accumulation and aggregation of amyloid in brain. Neuronostatin (NST) is an endogenous peptide hormone that participates in many fundamental neuronal processes. However, the metabolism and function of NST in neurons of AD mice are not known.
View Article and Find Full Text PDFFEBS Lett
August 2024
Department of Animal Physiology, Biochemistry and Biostructure, Poznań University of Life Sciences, Poznań, Poland.
Neuronostatin suppresses the differentiation of white preadipocytes. However, the role of neuronostatin in brown adipose tissue remains elusive. Therefore, we investigated the impact of neuronostatin on the proliferation and differentiation of isolated rat brown preadipocytes.
View Article and Find Full Text PDFPostepy Biochem
June 2023
Katedra Fizjologii, Biochemii i Biostruktury Zwierząt, Uniwersytet Przyrodniczy w Poznaniu.
Neuronostatin is a peptide hormone encoded by the somatostatin gene. Neuronostatin was discovered in 2008 using bioinformatics methods. Studies in rodents have shown that it exerts a widespread effects in the central nervous system, as well as in peripheral tissues.
View Article and Find Full Text PDFNeuropeptides
August 2022
College of Life Sciences, Northwest Normal University, Lanzhou, Gansu 730070, China. Electronic address:
Neuronostatin, a bioactive peptide hormone, was encoded by pro-somatostatin and discovered using a bioinformatic method in 2008. Neuronostatin is widely expressed in the central nervous system (CNS) and peripheral tissues, it is also highly conserved among humans, rodents, and even goldfish. The 13 and 19 amino acids and the C-terminal amidation type play important roles in physiological and pathological functions.
View Article and Find Full Text PDFEur J Endocrinol
September 2021
Center for Clinical Metabolic Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
In 2008, the first evidence of a new hormone called neuronostatin was published. The hormone was discovered using a bioinformatic method and found to originate from the same preprohormone as somatostatin. This small peptide hormone of 13 amino acids and a C-terminal amidation was soon found to exert pleiotropic physiological effects.
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