The long-range goals include elucidation of control mechanisms of gastrointestinal endocrine cell growth and replication. A further goal includes understanding of abnormal physiological or disease states characterized by disturbances in gastrointestinal endocrine function. This study will examine mechanisms of postvagotomy gastrin cell proliferation.
The specific aims are 1) investigation of the relationship between luminal pH and acute postvagotomy hypergastrinemia, 2) study of the relationships of circulating and tissue somatostatin and gastrin production and release early after vagotomy, 3) study of the time course and mechanisms of denervation-caused gastric endocrine cell proliferation, and 4) identification of changes in gastrin and somatostatin secretory responses to known secretagogues during proliferation and after hyperplastic adaptation. The rat will be the experimental animal. The effects of variations in luminal pH on gastrin release after vagotomy will be studied using an in vivo luminal gastric perfusion model. Investigations of somatostatin cell and gastrin cell responses to various secretagogues will employ an in vivo vascular gastric infusion system. Measurements of tissue hormone content, quantitation of DNA, RNA, and protein production, and estimation of mitotic activity by autoradiography will be used to study the mechanisms of gastric endocrine cell proliferation.
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