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We examined the cholecystokinin (CCK)-B/gastrin receptor, H[sup +] /K[sup +] -ATPase and somatostatin gene expression, the histology and immunohistochemistry of gastrin and somatostatin of the stomach, plasma gastrin levels, and gastric acid secretion in naturally occurring CCK-A receptor gene knockout (Otsuka Long-Evans Tokushima fatty, OLETF) rats. The CCK-B/gastrin receptor, H[sup +] /K[sup +] -ATPase and somatostatin mRNAs were determined by Northern transfer analysis. The gastric acid secretion and the plasma gastrin level were measured in vivo. The levels of CCK-B/gastrin receptor mRNA in the forestomach and the glandular stomach in OLETF rats were 2-fold higher than those of control rats, although those of H[sup +] /K[sup +] -ATPase and somatostatin mRNAs were not different. Histological examination revealed thickening of the fundic mucosa, and hyperplasia and hypertrophy of parietal cells, although immunohistochemistry of gastrin and somatostatin revealed no significant difference from the control rats. Gastric acid secretion stimulated by gastrin or histamine was enhanced, whereas the fasting plasma gastrin level was not significantly different from that in control rats. The overexpression of CCK-B/gastrin receptor mRNA and the hyperfunction of parietal cells were observed in rats without CCK-A receptor gene expression. [ABSTRACT FROM AUTHOR]

Expressions of the cholecystokinin (CCK)-A and -B receptor genes in human duodenum, pancreas and gallbladder were examined by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization. The autoradiographic study of CCK-A and -B receptors in the human duodenum and pancreas was examined in vitro. To determine the subtypes to CCK receptors in the pancreas or duodenum, we studied the abilities of CCK-A and -B receptor agonists (CCK-8 and gastrin) and antagonists (loxiglumide, L-364,718 and L-365,260) to inhibit binding of [sup 125] I-CCK-8. CCK-A receptor mRNA was not expressed in the human pancreas, but was expressed in the gallbladder and duodenum, although it was expressed in the pancreas by RT-PCR. CCK-B receptor mRNA was expressed in the pancreas, but not in gallbladder and duodenum. Using autoradiography, high concentrations of CCK-A receptors were detected in the duodenal mucosa, although in the pancreas only CCK-B receptors were detected by this method. These results suggest that localization of CCK-A receptor in human duodenum provides a biochemical and morphological basis for some physiological functions of CCK. [ABSTRACT FROM AUTHOR]

Abstract: We have characterized the regulation of human SH-2 containing inositol 5′-phosphatase 2 (SHIP2) gene expression. First, the transcription initiation sites and the sequence of the 5′ upstream region of human SHIP2 gene were elucidated. Next, the minimal promoter of the human SHIP2 gene was identified by reporter gene assays in HL60 cells and differentiated human subcutaneous white adipocytes. An Sp1 element proximal to the transcription initiation site was indispensable for full promoter activity and bound specifically by Sp1 and Sp3 proteins. These findings suggest that human SHIP2 gene expression, like other housekeeping genes, is controlled by the Sp-family of transcription factors. [Copyright &y& Elsevier]