Paradoxical antagonism of PACAP receptor signaling by VIP in Xenopus oocytes via the type-C natriuretic peptide receptor

Atrial natriuretic peptide (ANP) and the closely-related peptides BNP and CNP are highly conserved cardiovascular hormones. They bind to single transmembrane-spanning receptors, triggering receptor-intrinsic guanylyl cyclase activity. The “truncated” type-C natriuretic peptide receptor (NPR-C) has l...

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Bibliographic Details
Published in:Cellular signalling 2006-11, Vol.18 (11), p.2013-2021
Main Authors: Lelièvre, V., Hu, Z., Ioffe, Y., Byun, J.-Y., Flores, A., Seksenyan, A., Waschek, J.A.
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - metabolism
Amino Acid Sequence
Animals
Binding, Competitive
cAMP
Cloning, Molecular
DNA, Complementary - genetics
Humans
Molecular Sequence Data
Natriuretic peptide
Neuropeptide
Oocytes - drug effects
Oocytes - metabolism
Rats
Receptor
Receptors, Atrial Natriuretic Factor - genetics
Receptors, Atrial Natriuretic Factor - metabolism
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide - antagonists & inhibitors
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism
RNA, Messenger - metabolism
RNA, Messenger - pharmacology
Sequence Alignment
Signal Transduction
Signaling
Vasoactive Intestinal Peptide - metabolism
Vasoactive Intestinal Peptide - pharmacology
Xenopus
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Summary:Atrial natriuretic peptide (ANP) and the closely-related peptides BNP and CNP are highly conserved cardiovascular hormones. They bind to single transmembrane-spanning receptors, triggering receptor-intrinsic guanylyl cyclase activity. The “truncated” type-C natriuretic peptide receptor (NPR-C) has long been called a clearance receptor because it lacks the intracellular guanylyl cyclase domain, though data suggest it might negatively couple to adenylyl cyclase via G i. Here we report the molecular cloning and characterization of the Xenopus laevis type-C natriuretic peptide receptor ( XNPR-C). Analysis confirms the presence of a short intracellular C-terminus, as well as a high similarity to fish and mammalian NPR-C. Injection of XNPR-C mRNA into Xenopus oocytes resulted in expression of high affinity [ 125I]ANP binding sites that were competitively and completely displaced by natriuretic analogs and the unrelated neuropeptide vasoactive intestinal peptide (VIP). Measurement of cAMP levels in mRNA-injected oocytes revealed that XNPR-C is negatively coupled to adenylyl cyclase in a pertussis toxin-sensitive manner. When XNPR-C was co-expressed with PAC 1 receptors for pituitary adenylyl cyclase-activating polypeptide (PACAP), VIP and natriuretic peptides counteracted the cAMP induction by PACAP. These results suggest that VIP and natriuretic peptides can potentially modulate the action of PACAP in cells where these receptors are co-expressed.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2006.03.013