Expression of cholecystokinin a receptors in neurons innervating the rat stomach and intestine

C. Sternini, H. Wong, T. Pham, R. De Giorgio, Laurence J Miller, S. M. Kuntz, Jr Reeve J.R., J. H. Walsh, H. E. Raybould

Research output: Contribution to journalArticle

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Abstract

Background and Aims: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine. Methods: We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry. Results: Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor- transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK- A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50%, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density. Conclusions: CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor.

Original languageEnglish (US)
Pages (from-to)1136-1146
Number of pages11
JournalGastroenterology
Volume117
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

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Cholecystokinin A Receptor
Cholecystokinin Receptors
Intestines
Stomach
Neurons
Cholecystokinin
Tetragastrin
Ganglionectomy
Digestive System
CHO Cells
Antibodies
Vagotomy
Vasoactive Intestinal Peptide
Substance P
Gastric Mucosa
Abdomen
Small Intestine
Reflex

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sternini, C., Wong, H., Pham, T., De Giorgio, R., Miller, L. J., Kuntz, S. M., ... Raybould, H. E. (1999). Expression of cholecystokinin a receptors in neurons innervating the rat stomach and intestine. Gastroenterology, 117(5), 1136-1146. https://doi.org/10.1016/S0016-5085(99)70399-9

Expression of cholecystokinin a receptors in neurons innervating the rat stomach and intestine. / Sternini, C.; Wong, H.; Pham, T.; De Giorgio, R.; Miller, Laurence J; Kuntz, S. M.; Reeve J.R., Jr; Walsh, J. H.; Raybould, H. E.

In: Gastroenterology, Vol. 117, No. 5, 1999, p. 1136-1146.

Research output: Contribution to journalArticle

Sternini, C, Wong, H, Pham, T, De Giorgio, R, Miller, LJ, Kuntz, SM, Reeve J.R., J, Walsh, JH & Raybould, HE 1999, 'Expression of cholecystokinin a receptors in neurons innervating the rat stomach and intestine', Gastroenterology, vol. 117, no. 5, pp. 1136-1146. https://doi.org/10.1016/S0016-5085(99)70399-9
Sternini, C. ; Wong, H. ; Pham, T. ; De Giorgio, R. ; Miller, Laurence J ; Kuntz, S. M. ; Reeve J.R., Jr ; Walsh, J. H. ; Raybould, H. E. / Expression of cholecystokinin a receptors in neurons innervating the rat stomach and intestine. In: Gastroenterology. 1999 ; Vol. 117, No. 5. pp. 1136-1146.
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abstract = "Background and Aims: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine. Methods: We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry. Results: Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor- transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK- A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50{\%}, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density. Conclusions: CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor.",
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T1 - Expression of cholecystokinin a receptors in neurons innervating the rat stomach and intestine

AU - Sternini, C.

AU - Wong, H.

AU - Pham, T.

AU - De Giorgio, R.

AU - Miller, Laurence J

AU - Kuntz, S. M.

AU - Reeve J.R., Jr

AU - Walsh, J. H.

AU - Raybould, H. E.

PY - 1999

Y1 - 1999

N2 - Background and Aims: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine. Methods: We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry. Results: Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor- transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK- A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50%, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density. Conclusions: CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor.

AB - Background and Aims: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine. Methods: We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry. Results: Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor- transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK- A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50%, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density. Conclusions: CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor.

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