Peptides Derived from the Prohormone proNPQ/Spexin are Potent Central Modulators of Cardiovascular and Renal Function and Nociception

Abstract

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-NH₂) 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 (ED₅₀<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.—Toll, L., Khroyan, T. V., Sonmez, K., Ozawa, A., Lindberg, I., McLaughlin, J. P., Eans, S. O., Shahien, A. A., Kapusta, D. R. Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception. 

FASEB J. 26, 947–954 (2012). www.fasebj.org