Vol. 273, Issue 6, E1127-E1132, December 1997
A new biological contribution of cyclo(His-Pro) to the
peripheral inhibition of pancreatic secretion
Pascal
Fragner1,
Olivier
Presset2,
Nicole
Bernad3,
Jean
Martinez3,
Claude
Roze2, and
Sonia
Aratan-Spire1
1 Institut National de la
Santé et de la Recherche Médicale Unité 30,
Mécanisme d'Action Cellulaire des Hormones, Hôpital
Necker-Enfants-Malades, Tour Lavoisier, 75743 Paris Cedex 15;
2 Institut National de la
Santé et de la Recherche Médicale Unité 410,
Neuroendocrinologie et Biologie Cellulaire Digestives, 75870 Paris
Cedex 18; and 3 Centre
National de la Recherche Scientifique 5075, Université de
Montpellier I et II, Laboratoire des Aminopeptides, Peptides et
Proteines, Faculté de Pharmacie, 34060 Montpellier Cedex, France
The tripeptide
pyro-Glu-His-Pro-NH2
[thyrotropin-releasing hormone (TRH)] was isolated from the
hypothalamus as a thyrotropin-releasing factor. It has a broad spectrum
of central nervous system-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) dose dependently inhibited
2-deoxy-D-glucose
(2-DG)-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.
thyrotropin-releasing hormone; histidyl-proline diketopiperazine,
thyroliberinase; serum pyroglutamyl aminopeptidase; methyl
thyrotropin-releasing hormone
