A new biological contribution of cyclo his pro to the peripheral
inhibition of pancreatic secretion.
Fragner, Pascal, Olivier Presset, Nicole Bernad, Jean Martinez, Claude
Roze, and Sonia Aratan-Spire.
INSERM U 30, M[acute]ecanisme d'action cellulaire des hormones,
Hopital Necker-Enfants-Malades, Tour Lavoisier, 149 Rue de
S[grave]evres,75743 Paris Cedex 15, (PF, SA-S); INSERM U 410,
Neuroendocrinologie et Biologie Cellulaire Digestives,16 Rue H.
Huchard 75870 Paris Cedex 18, (OP, CR); ESA CNRS 5075,
Universit[acute]e de Montpellier I et II, Laboratoire des
Aminopeptides, Peptides et Proteines, Facult[acute]e de Pharmacie,15
Av. C. Flahault, 34060 Montpellier Cedex, (NB, JM), France.
APStracts 4:0196E, 1997.
The tripeptide pyroGlu-His-ProNH2 (TRH) was isolated from the
hypothalamus as a thyrotropin-releasing factor. It has a broad
spectrum of CNS-mediated actions, including the stimulation of
exocrine pancreatic secretion. TRH is also synthesized in the
endocrine pancreas and found in the systemic circulation. Enzymatic
degradation of TRH in vivo produces other bioactive peptides such as
cyclo His Pro. Because of the short half life of TRH and the
stability of cyclo His Pro in vivo, we postulated that at least part
of the peripheral TRH effects on the exocrine pancreatic secretion
may be attributed to cyclo His Pro which has been shown to have other
biological activities. This study determines in parallel the
peripheral effects of TRH and cyclo His Pro as well as the putative
contribution of other TRH-related peptides on exocrine pancreatic
secretion in rats. TRH and its metabolite cyclo His-Pro inhibited
dose-dependently 2-deoxy-D-glucose-stimulated pancreatic secretion.
TRH and all the related peptides tested had no effect on the basal
and cholecystokinin-stimulated amylase release from pancreatic acinar
cells in vitro. These data indicate that cyclo His-Pro mimics the
peripheral inhibitory effect of TRH on 2-DG stimulated exocrine
pancreatic secretion. This effect is not detected on isolated
pancreatic acini.
Our findings provide a new biological contribution for cyclo His-Pro
with potential experimental and clinical applications.
Received 14 July 1997; accepted in final form 4 September 1997.
APS Manuscript Number E331-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997