Overexpression of glycine-extended gastrin maintains acid secretion and prevents the development of preneoplasia in the stomach via reducing parietal cell lost in transgenic mice

Abstract

Background: CCK is one of the most abundant neurotransmitter peptides expressed in the brain. CCK-A receptor (R) is expressed in specific brain regions such as the amygdala, nucleus tractns solitarius, posterior nucleus accumbens, ventral tegmental area, hypothalamus, substantia nigra, hippocampus, area postrema, and raphe nucleus, whereas CCKBR is widely distributed throughout the central nervous system. Several reports including phamaacological studies have shown that the CCK-BR is involved in anxiety, while CCKAR has been implicated in satiety and behavior. However, the cross-reactivity of each antagonist could not be excluded in those studies, moreover, the expression patterns of these receptors o~,erlap in the brain/Aims: We recently generated the CCK-AR(-/-), BR(-/) and CCK-AR(-/-)BR(-/.) mice. Here we have examined the anxiety-related behavior of these mutant mice during the elevated plus-maze test. Methods: The animals were handled for 3 m/n/day for 3 days prior to the test. In each test, the following parameters were measured over a period of 5 rain (300 s); l) the frequency of entry into the open and enclosed arms of the maze (with an arm entry defined as the placing of all four paws into an arrd); 2) the proportion of time spent in the open and enclosed arms; and 3) the number of partial entries (the placing of only two paws) into the open arms. Results: CCK-AR(-/-) mice showed a significantly higher frequency/of open-arm entries than wild-type and CCK-BR(-/-) mice, whereas % open-arm entry values in CCK-AR(-/-) mice did not differ from those in wildtype mice. By contrast, CCK-BR(-/-) mice showed significantly lower % open-arm entry values and spent significantly less time in the openarms than wild-type and CCK-AR(-/-) mice. Although the frequency of open-arm entries for CCK-BR(-/-) mice was not significantly different from that for wild-type mice, it was significantly lower than that for CCK,AR(-/-) mice. The % open-arm entry values for CCK-BR(-/-) was significantly lower than those fdr wild-type and CCK-AR(-/-) mice. The time,/spent in the enclosed-arfns differed significantly among the four genotypes, and was significantly higher for both CCK-BR(-/-) arid CCKAR(-/-)BR(-/-) mice than for CCK-AR(-/-) and wild-type mice. Conclusions: A lack of CCKBR increases the anxiety-related behavior of the mouse in the elevated plusmaze. The discrepancy between previous pharmacological studies tflaf administration of a CCK-BR ligand induces anxiety and our resuh should be further investigated.