Immunohistochemical localization of CCK1 cholecystokinin receptors in normal and neoplastic human tissues.
BACKGROUND
The biological effects of cholecystokinin (CCK) are mediated by two distinct G protein-coupled receptors, CCK1 and CCK2. Although it is well established that CCK receptors are widely distributed throughout the normal gastrointestinal tract, little is known about their cellular and subcellular localization in human normal and neoplastic tissues.


METHODS
We developed and characterized a novel antipeptide antibody to the carboxyl-terminal region of the human CCK1 receptor. Specificity of the antiserum was demonstrated by 1) detection of a broad band migrating at a relative molecular mass of 85,000-95,000 in Western blots of membranes from CCK1-expressing tumors and CCK1-transfected cells, 2) cell surface staining of CCK1-transfected cells, 3) translocation of CCK1 receptor immunostaining after agonist exposure, and 4) abolition of tissue immunostaining by preadsorption of the antibody with its immunizing peptide. The distribution of CCK1 receptors was investigated in 74 human tumors and their tissues of origin.


RESULTS
The presence of CCK1 receptors was rarely detected in human tumors except for carcinoids, insulinomas, pituitary adenomas, and meningiomas. CCK1 receptors were clearly located at the plasma membrane and uniformly present on nearly all tumor cells. In the gastrointestinal tract, CCK1 receptor immunoreactivity was highly abundant in chief cells of the gastric mucosa, in myenteric ganglion cells, and in myenteric nerve fibers.


CONCLUSIONS
This is the first localization of CCK1 receptors in human formalin-fixed, paraffin-embedded tissues at the cellular level. The overexpression of CCK1 receptors in a subset of human neuroendocrine tumors may provide a molecular basis for efficient targeting of these tumors with radiolabeled CCK analogs.
Schulz
Stefan
S
Department of Pharmacology and Toxicology, Leipziger Strasse 44, 39120 Magdeburg, Germany. Stefan.Schulz@Medizin.Uni-Magdeburg.de
Röcken
Christoph
C
Mawrin
Christian
C
Schulz
Solveig
S
D000595:Amino Acid Sequence; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000737:chemistry*; D043886:Receptor, Cholecystokinin A / Q000032:analysis* / Q000276:immunology; D043887:Receptor, Cholecystokinin B / Q000032:analysis / Q000276:immunology
D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B