<p class="first" id="P1">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. [
<sup>125</sup>I]TLQP-21 was
<i>i.v.</i> administered in rats followed by chasing the plasma radioactivity and
assessing tissue
uptake. Plasma stability was measured using LC-MS.
<i>In vivo</i> lipolysis was assessed by the palmitate rate of appearance. Results:
A small single
<i>i. v.</i> dose of [
<sup>125</sup>I]TLQP-21 had a terminal half-life of 110 minutes with a terminal clearance
rate constant,
<i>k</i>
<sub>t</sub>, of 0.0063/min, and an initial half-life of 0.97 minutes with an initial
clearance
rate constant,
<i>k</i>
<sub>i</sub>, 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
<i>in vivo.</i> Finally, TLQP-21 was rapidly degraded producing several N-terminal
and central sequence
fragments after 10 and 60 minutes in plasma
<i>in vitro.</i> 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.
</p>