GASTROINTESTINAL SIGNIFICANCE OF GASTRIN REGULATION

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DESCRIPTION (Adapted from the applicant's abstract): This is a proposal to continue studies on the properties and function of the gastrin/CCK-B receptor and a putative receptor for Gly-extended gastrin (G-Gly). During the previous funding period, the PI and his collaborators have shown that the Gly-extended intermediate, an obligatory precursor of amidated gastrin, is stored with gastrin and secreted with it in response to physiological stimuli. Gly-extended gastrin was shown to stimulate cell growth via a separate receptor. The binding of the gastrin/CCK-B receptor and the structural requirements for activation of G proteins were also studied. Several key components of transcriptional regulation of the gastrin/CCK-B receptor gene were identified. The present proposal is designed to extend these studies. The following specific aims will be pursued. 1) elucidate the structural components of the gastrin/CCK-B receptor that are important in determining cell growth and secretion; 2) characterize the structural components of the gastrin/CCK-B receptor gene that are important in determining its expression and function; 3) examine the post-receptor events linked to cell growth mediated by Gly-extended gastrin; and 4) further characterize the receptor for Gly-extended gastrin and clone its corresponding cDNA.