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Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide.
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- Additional Information
- Source:
Publisher: Published by Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 2984726R Publication Model: Print Cited Medium: Print ISSN: 0264-6021 (Print) Linking ISSN: 02646021 NLM ISO Abbreviation: Biochem J Subsets: MEDLINE
- Publication Information:
Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society
- Subject Terms:
- Abstract:
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) exert their physiological actions by binding to natriuretic peptide receptor A (NPRA), a receptor guanylate cyclase (rGC) that synthesizes cGMP in response to both ligands. The family of rGCs is rapidly expanding, and it is plausible that there might be additional, as yet undiscovered, rGCs whose function is to provide alternative signalling pathways for one or both of these peptides, particularly given the low affinity of NPRA for BNP. We have investigated this hypothesis, using a genetically modified (knockout) mouse in which the gene encoding NPRA has been disrupted. Enzyme assays and NPRA-specific Western blots performed on tissues from wild-type mice demonstrate that ANP-activated cGMP synthesis provides a good index of NPRA protein expression, which ranges from maximal in adrenal gland, lung, kidney, and testis to minimal in heart and colon. In contrast, immunoreactive NPRA is not detectable in tissues isolated from NPRA knockout animals and ANP- and BNP-stimulatable GC activities are markedly reduced in all mutant tissues. However, testis and adrenal gland retain statistically significant, high-affinity responses to BNP. This residual response to BNP cannot be accounted for by natriuretic peptide receptor B, or any other known mammalian rGC, suggesting the presence of a novel receptor in these tissues that prefers BNP over ANP.
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- Grant Information:
DK34987 United States DK NIDDK NIH HHS; GM20069 United States GM NIGMS NIH HHS; HL49277 United States HL NHLBI NIH HHS
- Accession Number:
114471-18-0 (Natriuretic Peptide, Brain)
127869-51-6 (Natriuretic Peptide, C-Type)
85637-73-6 (Atrial Natriuretic Factor)
EC 4.6.1.2 (Guanylate Cyclase)
EC 4.6.1.2 (Receptors, Atrial Natriuretic Factor)
EC 4.6.1.2 (atrial natriuretic factor receptor A)
EC 4.6.1.2 (atrial natriuretic factor receptor B)
H2D2X058MU (Cyclic GMP)
- Publication Date:
Date Created: 20010822 Date Completed: 20011004 Latest Revision: 20190501
- Publication Date:
20221213
- Accession Number:
PMC1222070
- Accession Number:
10.1042/0264-6021:3580379
- Accession Number:
11513736
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