Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin

Baoan D Ji, Yan Bi, Diane Simeone, Richard M. Mortensen, Craig D. Logsdon

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Background & Aims: Pancreatic acinar cells from various species express cholecystokinin (CCK) A, CCK-B, or a combination of these CCK receptor subtypes. The presence and functional roles of CCK receptors on human acinar cells remain unclear. Methods: Acini isolated from human pancreas were treated with CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscarinic acetylcholine receptors (m3 AchR), carbachol. Functional parameters measured included intracellular [Ca 2+], amylase secretion, and ERK phosphorylation. Binding studies were performed using 125I-CCK-8. Expression of messenger RNAs (mRNAs) was determined using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and localized by in situ hybridization. Results: Human acini did not respond to CCK agonists. In contrast, they responded to carbachol with robust increases in each of the functional parameters. Moreover, the cells responded to CCK agonists after adenoviral-mediated gene transfer of CCK-A or CCK-B receptors. A low level of specific and a high level of nonspecific binding of 125I-CCK-8 were observed. Quantitative RT-PCR indicated that the message levels for CCK-A receptors were @O30-fold lower than those of CCK-B receptors, which were @O10-fold lower than those of m3 Ach receptors. In situ hybridization indicated the presence of m3 Ach receptor and insulin mRNA but not CCK-A or CCK-B receptor mRNAs in adult human pancreas. Conclusions: These data indicate that human pancreatic acinar cells do not respond to CCK receptor agonists in terms of expected functional parameters and show that this is due to an insufficient level of receptor expression.

Original languageEnglish (US)
Pages (from-to)1380-1390
Number of pages11
JournalGastroenterology
Volume121
Issue number6
StatePublished - 2001
Externally publishedYes

Fingerprint

Acinar Cells
Cholecystokinin
Gastrins
Cholecystokinin Receptors
Cholecystokinin B Receptor
Carbachol
Messenger RNA
Reverse Transcription
In Situ Hybridization
Pancreas
Cholecystokinin A Receptor
Polymerase Chain Reaction
Insulin Receptor
Muscarinic Receptors
Amylases
Phosphorylation
Genes
cholecystokinin 8

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ji, B. D., Bi, Y., Simeone, D., Mortensen, R. M., & Logsdon, C. D. (2001). Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin. Gastroenterology, 121(6), 1380-1390.

Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin. / Ji, Baoan D; Bi, Yan; Simeone, Diane; Mortensen, Richard M.; Logsdon, Craig D.

In: Gastroenterology, Vol. 121, No. 6, 2001, p. 1380-1390.

Research output: Contribution to journalArticle

Ji, BD, Bi, Y, Simeone, D, Mortensen, RM & Logsdon, CD 2001, 'Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin', Gastroenterology, vol. 121, no. 6, pp. 1380-1390.
Ji, Baoan D ; Bi, Yan ; Simeone, Diane ; Mortensen, Richard M. ; Logsdon, Craig D. / Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin. In: Gastroenterology. 2001 ; Vol. 121, No. 6. pp. 1380-1390.
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AU - Simeone, Diane

AU - Mortensen, Richard M.

AU - Logsdon, Craig D.

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N2 - Background & Aims: Pancreatic acinar cells from various species express cholecystokinin (CCK) A, CCK-B, or a combination of these CCK receptor subtypes. The presence and functional roles of CCK receptors on human acinar cells remain unclear. Methods: Acini isolated from human pancreas were treated with CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscarinic acetylcholine receptors (m3 AchR), carbachol. Functional parameters measured included intracellular [Ca 2+], amylase secretion, and ERK phosphorylation. Binding studies were performed using 125I-CCK-8. Expression of messenger RNAs (mRNAs) was determined using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and localized by in situ hybridization. Results: Human acini did not respond to CCK agonists. In contrast, they responded to carbachol with robust increases in each of the functional parameters. Moreover, the cells responded to CCK agonists after adenoviral-mediated gene transfer of CCK-A or CCK-B receptors. A low level of specific and a high level of nonspecific binding of 125I-CCK-8 were observed. Quantitative RT-PCR indicated that the message levels for CCK-A receptors were @O30-fold lower than those of CCK-B receptors, which were @O10-fold lower than those of m3 Ach receptors. In situ hybridization indicated the presence of m3 Ach receptor and insulin mRNA but not CCK-A or CCK-B receptor mRNAs in adult human pancreas. Conclusions: These data indicate that human pancreatic acinar cells do not respond to CCK receptor agonists in terms of expected functional parameters and show that this is due to an insufficient level of receptor expression.

AB - Background & Aims: Pancreatic acinar cells from various species express cholecystokinin (CCK) A, CCK-B, or a combination of these CCK receptor subtypes. The presence and functional roles of CCK receptors on human acinar cells remain unclear. Methods: Acini isolated from human pancreas were treated with CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscarinic acetylcholine receptors (m3 AchR), carbachol. Functional parameters measured included intracellular [Ca 2+], amylase secretion, and ERK phosphorylation. Binding studies were performed using 125I-CCK-8. Expression of messenger RNAs (mRNAs) was determined using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and localized by in situ hybridization. Results: Human acini did not respond to CCK agonists. In contrast, they responded to carbachol with robust increases in each of the functional parameters. Moreover, the cells responded to CCK agonists after adenoviral-mediated gene transfer of CCK-A or CCK-B receptors. A low level of specific and a high level of nonspecific binding of 125I-CCK-8 were observed. Quantitative RT-PCR indicated that the message levels for CCK-A receptors were @O30-fold lower than those of CCK-B receptors, which were @O10-fold lower than those of m3 Ach receptors. In situ hybridization indicated the presence of m3 Ach receptor and insulin mRNA but not CCK-A or CCK-B receptor mRNAs in adult human pancreas. Conclusions: These data indicate that human pancreatic acinar cells do not respond to CCK receptor agonists in terms of expected functional parameters and show that this is due to an insufficient level of receptor expression.

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