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Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception.

Authors: Toll, L  Khroyan, TV  Sonmez, K  Ozawa, A  Lindberg, I  McLaughlin, JP  Eans, SO  Shahien, AA  Kapusta, DR 
Citation: Toll L, etal., FASEB J. 2012 Feb;26(2):947-54. doi: 10.1096/fj.11-192831. Epub 2011 Oct 28.
Pubmed: (View Article at PubMed) PMID:22038051
DOI: Full-text: DOI:10.1096/fj.11-192831

Computational methods have led two groups to predict the endogenous presence of a highly conserved, amidated, 14-aa neuropeptide called either spexin or NPQ. NPQ/spexin is part of a larger prohormone that contains 3 sets of RR residues, suggesting that it could yield more than one bioactive peptide; however, no in vivo activity has been demonstrated for any peptide processed from this precursor. Here we demonstrate biological activity for two peptides present within proNPQ/spexin. NPQ/spexin (NWTPQAMLYLKGAQ-NH(2)) and NPQ 53-70 (FISDQSRRKDLSDRPLPE) have differing renal and cardiovascular effects when administered intracerebroventricularly or intravenously into rats. Intracerebroventricular injection of NPQ/spexin produced a 13 +/- 2 mmHg increase in mean arterial pressure, a 38 +/- 8 bpm decrease in heart rate, and a profound decrease in urine flow rate. Intracerebroventricular administration of NPQ 53-70 produced a 26 +/- 9 bpm decrease in heart rate with no change in mean arterial pressure, and a marked increase in urine flow rate. Intraventricular NPQ/spexin and NPQ 53-70 also produced antinociceptive activity in the warm water tail withdrawal assay in mice (ED(50)<30 and 10 nmol for NPQ/spexin and NPQ 53-70, respectively). We conclude that newly identified peptides derived from the NPQ/spexin precursor contribute to CNS-mediated control of arterial blood pressure and salt and water balance and modulate nociceptive responses.

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CRRD Object Information
CRRD ID: 8693358
Created: 2014-07-11
Species: All species
Last Modified: 2014-07-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.