Numerous cell targets for gastrin in the guinea pig stomach revealed by gastrin/CCK B receptor localization

Abstract

The localization of the gastrin/CCKB receptor (GR) has recently become a subject of debate, especially since the publication of evidence for its presence in an unsuspected location, namely in the lamina propria, the submucosal layer of the stomach lining. Knowledge of the receptor localization is important because of the critical role of gastrin secretion and its trophic effects on the gastric epithelium. The present study, which utilizes immunohistochemistry and electron microscopy as primary tools, provides unequivocal data concerning the localization of GR in the guinea pig stomach. GR is expressed in parietal cells, on chief cells, and in previously unreported endocrine cells of the stomach. It is not found in the lamina propria. The predominant localization of the receptor in the endocrine cells is on the membranes of cytoplasmic electron-dense secretory granules. The positioning of these cells in the gastric glands suggests that they may be involved in the uptake of gastrin from the circulation. The distribution of GR implies that it may be involved in the regulation of various processes and may mediate various effects of gastrin in the stomach.

Gastrin stimulates the growth of gastric pit cell precursors by inducing its own receptors

“…For example, they showed less binding to pit cell-specific CTB lectin, although the pit region was extensively elongated. In previous studies, CCKB-Rs were localized in parietal, chief, and ECL cells (28,41). Thus the CCKB-R-positive cells in the lower glands in control mice appear to be a mixture of these cells.…”

“…CCKA-Rs exhibit a 500-to 1,000-fold higher affinity for sulfated analogs of CCK than for gastrin, whereas CCKB-Rs have approximately equal affinity for both sulfated and non-sulfated peptide analogs of CCK and gastrin (32,34,46,47). CCKB-Rs are present in parietal, ECL, and probably somatostatin cells (2,4,23,27,28,41 (2,28). Immunohistochemical studies have also demonstrated the distribution of CCKB-R in the same cell types (41).…”

“…CCKB-Rs are present in parietal, ECL, and probably somatostatin cells (2,4,23,27,28,41 (2,28). Immunohistochemical studies have also demonstrated the distribution of CCKB-R in the same cell types (41). On the other hand, Matsuda et al (23) reported no specific binding of [ 125 I]gastrin to guinea pig gastric epithelial cells in culture, most of which displayed periodic acid-Schiff (PAS)-positive granules, characteristic of pit cells.…”

Cholecystokinin and Gastrin Receptors

“…Binding and functional studies demonstrated that both CCK1R and CCK2R are present on guinea pig chief cells (91, 389). In addition to detection on parietal and chief cells in the guinea pig stomach, CCK2R was also detected on rare unidentified endocrine cells that were negative for gastrin, histamine, secretin, somatostatin, enkephalin, and gastrin-releasing peptide (521). Precise cellular localization of human stomach CCK2R by in situ RT-PCR and immunohistochemistry demonstrated expression in gastric parietal, ECL, and putative precursor cells (261,451).…”

Cytotoxic agents directed to peptide hormone receptors: Defining the requirements for a successful drug

“…Tumors grown in athymic mice were trimmed to pieces not more than 0.5 cm in each dimension and fixed in 4% formaldehyde in PBS for 16 h at 4°C. Fixed specimens were processed to sections and stained with rabbit polyclonal antibodies to CCKBR as described (34).…”