Clearance kinetics of the VGF-derived neuropeptide TLQP-21

Zeng Kui Guo, Bhavani S. Sahu, Rongjun He, Brian Finan, Cheryl Cero, Raffaello Verardi, Maria Razzoli, Gianluigi Veglia, Richard D. Di Marchi, John M. Miles, Alessandro Bartolomucci

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

TLQP-21 is a multifunctional neuropeptide and a promising new medicinal target for cardiometabolic and neurological diseases. However, to date its clearance kinetics and plasma stability have not been studied. The presence of four arginine residues led us to hypothesize that its half-life is relatively short. Conversely, its biological activities led us to hypothesize that the peptide is still taken up by adipose tissues effectively. [125I]TLQP-21 was i.v. administered in rats followed by chasing the plasma radioactivity and assessing tissue uptake. Plasma stability was measured using LC-MS. In vivo lipolysis was assessed by the palmitate rate of appearance. Results: A small single i.v. dose of [125I]TLQP-21 had a terminal half-life of 110 min with a terminal clearance rate constant, kt, of 0.0063/min, and an initial half-life of 0.97 min with an initial clearance rate constant, ki, of 0.71/min. The total net uptake by adipose tissue accounts for 4.4% of the entire dose equivalent while the liver, pancreas and adrenal gland showed higher uptake. Uptake by the brain was negligible, suggesting that i.v.-injected peptide does not cross the blood-brain-barrier. TLQP-21 sustained isoproterenol-stimulated lipolysis in vivo. Finally, TLQP-21 was rapidly degraded producing several N-terminal and central sequence fragments after 10 and 60 min in plasma in vitro. This study investigated the clearance and stability of TLQP-21 peptide for the first time. While its pro-lipolytic effect supports and extends previous findings, its short half-life and sequential cleavage in the plasma suggest strategies for chemical modifications in order to enhance its stability and therapeutic efficacy.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalNeuropeptides
Volume71
DOIs
StatePublished - Oct 2018

Keywords

  • Adipose tissue
  • Complement 3a receptor 1
  • Isotopes
  • Lipolysis
  • Pharmacokinetics
  • Rats
  • Tissue uptake

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Clearance kinetics of the VGF-derived neuropeptide TLQP-21'. Together they form a unique fingerprint.

  • Cite this

    Guo, Z. K., Sahu, B. S., He, R., Finan, B., Cero, C., Verardi, R., Razzoli, M., Veglia, G., Di Marchi, R. D., Miles, J. M., & Bartolomucci, A. (2018). Clearance kinetics of the VGF-derived neuropeptide TLQP-21. Neuropeptides, 71, 97-103. https://doi.org/10.1016/j.npep.2018.06.003