RGD Reference Report - Atrial natriuretic peptide-C receptor-induced attenuation of adenylyl cyclase signaling activates phosphatidylinositol turnover in A10 vascular smooth muscle cells. - Rat Genome Database

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Atrial natriuretic peptide-C receptor-induced attenuation of adenylyl cyclase signaling activates phosphatidylinositol turnover in A10 vascular smooth muscle cells.

Authors: Mouawad, R  Li, Y  Anand-Srivastava, MB 
Citation: Mouawad R, etal., Mol Pharmacol. 2004 Apr;65(4):917-24.
RGD ID: 1581459
Pubmed: PMID:15044621   (View Abstract at PubMed)
DOI: DOI:10.1124/mol.65.4.917   (Journal Full-text)

Atrial natriuretic peptide (ANP)-C receptor activation has been shown to inhibit adenylyl cyclase (AC) activity as well as to stimulate phospholipase C (PLC) signaling pathways. The present studies were undertaken to investigate whether ANP-C receptor-mediated decreased cAMP levels contribute to the activation of PLC signaling. C-ANP(4-23) [des(Gln(18),Ser(19), Glu(20),Leu(21),Gly(22))ANP(4-23)-NH(2)], a ring-deleted peptide of ANP that interacts specifically with ANP-C receptor, stimulated inositol 1,4,5-tris-phosphate (IP(3)) production (PLC activity) in A10 vascular smooth muscle cells in a concentration- and time-dependent manner. The maximal stimulation observed was about 75% at 2 h of treatment, with an apparent EC(50) of about 20 to 30 nM. Pertussis toxin treatment of the cells completely abolished the C-ANP(4-23)-mediated stimulation of IP(3) production. Forskolin (FSK), a stimulator of adenylyl cyclase, dibutyryl cAMP (db cAMP), and isoproterenol (ISO), a beta-adrenergic agonist that stimulates adenylyl cyclase activity and cAMP levels, inhibited IP(3) production by about 35, 30, and 50%, respectively, whereas dideoxyadenosine (DDA), an inhibitor of adenylyl cyclase activity, and oxotremorine stimulated IP(3) production by about 90 and 80%, respectively, in these cells, suggesting a functional interaction between these two signaling pathways. Treatment of the cells with antisense oligonucleotide of ANP-C receptor that attenuated ANP-C receptor-mediated inhibition of adenylyl cyclase resulted in a complete attenuation of C-ANP(4-23)-induced stimulation of IP(3) formation, whereas FSK, db cAMP, and ISO-mediated decrease and oxotremorine and endothelin-1 (ET-1)-induced increase in IP(3) production was not affected by this treatment. Furthermore, C-ANP(4-23)-induced increase in IP(3) formation was significantly potentiated by DDA and inhibited by FSK and db cAMP, whereas ET-1-induced increase in IP(3) production was not affected by FSK. In addition, N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H-89), an inhibitor of protein kinase A, completely abolished C-ANP(4-23) and not ET-1-induced stimulation of IP(3) production. These results indicate that ANP-C receptor activation by C-ANP(4-23) and resulting decrease in cAMP levels may be responsible for the activation of phosphatidylinositol (PI) turnover signaling, suggesting a cross-talk between ANP-C receptor-mediated adenylyl cyclase and PLC signaling pathways.



Gene Ontology Annotations    

Biological Process

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Npr3  (natriuretic peptide receptor 3)

Genes (Mus musculus)
Npr3  (natriuretic peptide receptor 3)

Genes (Homo sapiens)
NPR3  (natriuretic peptide receptor 3)


Additional Information