Actions of novel bombesin receptor antagonists on pancreatic secretion in

Jolanta Jaworek, Piotr K. Konturek, Stanislaw J. Konturek, Ren Zhi Cai, Andrew V Schally

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Recently synthezised highly specific and potent bombesin receptor antagonist permit study of the role of endogenous bombesin-like peptides in the physiological regulation of pancreatic secretion. We now tested the action of three novel pseudononapeptide bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095, RC-3100 and RC-3120) on amylase release in vitro from isolated rat pancreatic acini and on protein secretion in vivo in chronic pancreatic fistula rats. In isolated pancreatic acini, all three bombesin receptor antagonists inhibited the amylase secretion induced by bombesin by shifting to the right the amylase response to bombesin without altering the maximal response. These antagonists also reduced concentration dependently the near-maximal amylase response to bombesin, the concentration required for 50% reduction (IC50) being about 10-7 M for RC-3095 and RC-3100 and 10-6 M for RC-3120. None of the bombesin/GRP anatagonists used affected the amylase response to CCK, pentagastrin or urecholine. In conscious rate witha chronic pancreatic fistula, all three bombesin antagonists shifted to the right the pancreatic protein response to graded doses of bombesin without changing the maximal response. These antagonists inhibited the protein response to constant background stimulation with bombesin in a dose-dependent manner, the ID50 being about 20 nmol/kg per h for RC-3095 and RC-3100 and about 160 nmol/kg per h for RC-3120. None of the antagonists significantly affected basal pancreatic secretion or secretion induced by sham-feeding, ordinary feeding or the diversion of pancreatic juice from the duodenum. These results indicate that exogenous bombesin is a potent direct stimulant of pancreatic enzyme secretion. However, the results do not support the view that endogenous bombesin/GRP-like peptides are involved in the physiological regulation of pancreatic secretion in rats.

Original languageEnglish
Pages (from-to)239-245
Number of pages7
JournalEuropean Journal of Pharmacology
Volume214
Issue number2-3
DOIs
StatePublished - Apr 22 1992
Externally publishedYes

Fingerprint

Bombesin Receptors
Bombesin
Amylases
Gastrin-Releasing Peptide
Pancreatic Fistula
Bethanechol
Pancreatic Juice
Pentagastrin
Peptides
Proteins
Duodenum
Inhibitory Concentration 50

Keywords

  • Amylase
  • Bombesin
  • Bombesin receptor antagonists
  • Pancreatic secretion

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Actions of novel bombesin receptor antagonists on pancreatic secretion in. / Jaworek, Jolanta; Konturek, Piotr K.; Konturek, Stanislaw J.; Cai, Ren Zhi; Schally, Andrew V.

In: European Journal of Pharmacology, Vol. 214, No. 2-3, 22.04.1992, p. 239-245.

Research output: Contribution to journalArticle

Jaworek, Jolanta ; Konturek, Piotr K. ; Konturek, Stanislaw J. ; Cai, Ren Zhi ; Schally, Andrew V. / Actions of novel bombesin receptor antagonists on pancreatic secretion in. In: European Journal of Pharmacology. 1992 ; Vol. 214, No. 2-3. pp. 239-245.
@article{977e8d4ef3784857a9b2cc23bc275692,
title = "Actions of novel bombesin receptor antagonists on pancreatic secretion in",
abstract = "Recently synthezised highly specific and potent bombesin receptor antagonist permit study of the role of endogenous bombesin-like peptides in the physiological regulation of pancreatic secretion. We now tested the action of three novel pseudononapeptide bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095, RC-3100 and RC-3120) on amylase release in vitro from isolated rat pancreatic acini and on protein secretion in vivo in chronic pancreatic fistula rats. In isolated pancreatic acini, all three bombesin receptor antagonists inhibited the amylase secretion induced by bombesin by shifting to the right the amylase response to bombesin without altering the maximal response. These antagonists also reduced concentration dependently the near-maximal amylase response to bombesin, the concentration required for 50{\%} reduction (IC50) being about 10-7 M for RC-3095 and RC-3100 and 10-6 M for RC-3120. None of the bombesin/GRP anatagonists used affected the amylase response to CCK, pentagastrin or urecholine. In conscious rate witha chronic pancreatic fistula, all three bombesin antagonists shifted to the right the pancreatic protein response to graded doses of bombesin without changing the maximal response. These antagonists inhibited the protein response to constant background stimulation with bombesin in a dose-dependent manner, the ID50 being about 20 nmol/kg per h for RC-3095 and RC-3100 and about 160 nmol/kg per h for RC-3120. None of the antagonists significantly affected basal pancreatic secretion or secretion induced by sham-feeding, ordinary feeding or the diversion of pancreatic juice from the duodenum. These results indicate that exogenous bombesin is a potent direct stimulant of pancreatic enzyme secretion. However, the results do not support the view that endogenous bombesin/GRP-like peptides are involved in the physiological regulation of pancreatic secretion in rats.",
keywords = "Amylase, Bombesin, Bombesin receptor antagonists, Pancreatic secretion",
author = "Jolanta Jaworek and Konturek, {Piotr K.} and Konturek, {Stanislaw J.} and Cai, {Ren Zhi} and Schally, {Andrew V}",
year = "1992",
month = "4",
day = "22",
doi = "10.1016/0014-2999(92)90124-M",
language = "English",
volume = "214",
pages = "239--245",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Actions of novel bombesin receptor antagonists on pancreatic secretion in

AU - Jaworek, Jolanta

AU - Konturek, Piotr K.

AU - Konturek, Stanislaw J.

AU - Cai, Ren Zhi

AU - Schally, Andrew V

PY - 1992/4/22

Y1 - 1992/4/22

N2 - Recently synthezised highly specific and potent bombesin receptor antagonist permit study of the role of endogenous bombesin-like peptides in the physiological regulation of pancreatic secretion. We now tested the action of three novel pseudononapeptide bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095, RC-3100 and RC-3120) on amylase release in vitro from isolated rat pancreatic acini and on protein secretion in vivo in chronic pancreatic fistula rats. In isolated pancreatic acini, all three bombesin receptor antagonists inhibited the amylase secretion induced by bombesin by shifting to the right the amylase response to bombesin without altering the maximal response. These antagonists also reduced concentration dependently the near-maximal amylase response to bombesin, the concentration required for 50% reduction (IC50) being about 10-7 M for RC-3095 and RC-3100 and 10-6 M for RC-3120. None of the bombesin/GRP anatagonists used affected the amylase response to CCK, pentagastrin or urecholine. In conscious rate witha chronic pancreatic fistula, all three bombesin antagonists shifted to the right the pancreatic protein response to graded doses of bombesin without changing the maximal response. These antagonists inhibited the protein response to constant background stimulation with bombesin in a dose-dependent manner, the ID50 being about 20 nmol/kg per h for RC-3095 and RC-3100 and about 160 nmol/kg per h for RC-3120. None of the antagonists significantly affected basal pancreatic secretion or secretion induced by sham-feeding, ordinary feeding or the diversion of pancreatic juice from the duodenum. These results indicate that exogenous bombesin is a potent direct stimulant of pancreatic enzyme secretion. However, the results do not support the view that endogenous bombesin/GRP-like peptides are involved in the physiological regulation of pancreatic secretion in rats.

AB - Recently synthezised highly specific and potent bombesin receptor antagonist permit study of the role of endogenous bombesin-like peptides in the physiological regulation of pancreatic secretion. We now tested the action of three novel pseudononapeptide bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095, RC-3100 and RC-3120) on amylase release in vitro from isolated rat pancreatic acini and on protein secretion in vivo in chronic pancreatic fistula rats. In isolated pancreatic acini, all three bombesin receptor antagonists inhibited the amylase secretion induced by bombesin by shifting to the right the amylase response to bombesin without altering the maximal response. These antagonists also reduced concentration dependently the near-maximal amylase response to bombesin, the concentration required for 50% reduction (IC50) being about 10-7 M for RC-3095 and RC-3100 and 10-6 M for RC-3120. None of the bombesin/GRP anatagonists used affected the amylase response to CCK, pentagastrin or urecholine. In conscious rate witha chronic pancreatic fistula, all three bombesin antagonists shifted to the right the pancreatic protein response to graded doses of bombesin without changing the maximal response. These antagonists inhibited the protein response to constant background stimulation with bombesin in a dose-dependent manner, the ID50 being about 20 nmol/kg per h for RC-3095 and RC-3100 and about 160 nmol/kg per h for RC-3120. None of the antagonists significantly affected basal pancreatic secretion or secretion induced by sham-feeding, ordinary feeding or the diversion of pancreatic juice from the duodenum. These results indicate that exogenous bombesin is a potent direct stimulant of pancreatic enzyme secretion. However, the results do not support the view that endogenous bombesin/GRP-like peptides are involved in the physiological regulation of pancreatic secretion in rats.

KW - Amylase

KW - Bombesin

KW - Bombesin receptor antagonists

KW - Pancreatic secretion

UR - http://www.scopus.com/inward/record.url?scp=0026579722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026579722&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(92)90124-M

DO - 10.1016/0014-2999(92)90124-M

M3 - Article

C2 - 1381317

AN - SCOPUS:0026579722

VL - 214

SP - 239

EP - 245

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2-3

ER -