Different affinity states of CCK1 receptors on pancreatic acini and gastric smooth muscle in the rat

Krisztina Kisfalvi, Gábor Rácz, Attila Zsirka-Klein, Iva Pelosini, Carmelo Scarpignato, G. Varga

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

It has recently been shown that - after chronic cholecystokinin (CCK) treatment - an adaptation of pancreatic secretory but not gastric motor function does occur. Recent studies indicate that the CCK1-receptor exists in two (i.e. high and low) affinity states, which could be distinguished by the CCK-analogue JMV-180. CCK occupancy of high and low affinity sites is thought to be related to the initiation of different intracellular events and consequent biological responses. Affinity states of CCK1-receptors on pancreas and gastrointestinal (GI) smooth muscle could be different and this can offer an explanation for the different effects of CCK on pancreatic and gastric growth. We therefore studied the affinity states of CCK1-receptors on isolated rat pancreatic acini and gastric smooth muscle preparations. When acini were incubated with increasing concentrations of CCK-8, a biphasic (i.e. stimulation followed by inhibition) effect on amylase release was observed. JMV-180 caused only stimulation of enzyme release and combined JMV-180 and CCK stimulation (at submaximal doses) resulted in an additive secretory response. CCK-8 induced contractions of pyloric, antral and fundic muscle in a concentration-dependent manner. The response was monophasic, reaching a plateau. JMV-180 had only a very weak effect on these preparations. On the contrary, it inhibited CCK-induced contractions in a competitive manner, the concentration-response curve to CCK being shifted to the right by the CCK analogue. Our data suggest that the affinity states of CCK1-receptors on rat pancreatic and gastric tissue are different. On pancreatic acini CCK1-receptors exist in both high- and low-affinity states whose occupation is followed by the sequence of intracellular events leading to growth. In contrast, occupation of low affinity receptors (the only ones present in the GI smooth muscle) does not lead to cell proliferation. This difference therefore explains the different adaptive response of the pancreas and the stomach to chronic CCK administration. Furthermore, different affinity states of CCK1-receptors may mediate different functions of the digestive tract.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalJournal of Physiology Paris
Volume95
Issue number1-6
DOIs
Publication statusPublished - 2001

Fingerprint

Cholecystokinin
Smooth Muscle
Stomach
Occupations
Pancreas
Amylases
Growth
Gastrointestinal Tract
Cell Proliferation
Muscles
JMV 180
Enzymes

Keywords

  • Amylase secretion
  • CCK-receptors
  • Cholecystokinin
  • Contraction
  • Exocrine pancreas
  • Gastric smooth muscle
  • High affinity
  • JMV-180
  • Low affinity
  • Stomach

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology (medical)

Cite this

Different affinity states of CCK1 receptors on pancreatic acini and gastric smooth muscle in the rat. / Kisfalvi, Krisztina; Rácz, Gábor; Zsirka-Klein, Attila; Pelosini, Iva; Scarpignato, Carmelo; Varga, G.

In: Journal of Physiology Paris, Vol. 95, No. 1-6, 2001, p. 391-398.

Research output: Contribution to journalArticle

Kisfalvi, Krisztina ; Rácz, Gábor ; Zsirka-Klein, Attila ; Pelosini, Iva ; Scarpignato, Carmelo ; Varga, G. / Different affinity states of CCK1 receptors on pancreatic acini and gastric smooth muscle in the rat. In: Journal of Physiology Paris. 2001 ; Vol. 95, No. 1-6. pp. 391-398.
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