The longterm goal of this program is to describe the sequence of cellular reactions which lead to the secretion of hydrochloric acid by the gastric mucosa with emphasis on those reactions which serve as the major controlling steps. Recent interest in this area derives from the success of antisecretory agents in the clinical management of ulcer disease and the appreciation of the important role of proton transport in various biological processes. The current proposal seeks to extend previous observations concerning the cellular control of acid secretion so as to provide a more detailed understanding of the control mechanisms. Projects will utilize the recently developed preparations of isolated gastric glands and digitonin-permeabilized cells as well as the more traditional amphibian gastric mucosa as in vitro models. A combination of modern biophysical, biochemical, and morphological techniques will be used to investigate selected aspects of cellular control mechanisms. The major areas to be investigated include: 1) regulation of histamine H2-receptor; 2) the role of protein kinases, specifically the cAMP-dependent and calcium/phospholipid-dependent enzymes; 3) the basic mechanisms involved in the morphological transition of the parietal cell which occurs with stimulation; 4) the relationship between mitochondrial metabolism and proton transport; and 5) the effects of omeprazole, an H-KATPase inhibitor, on ion transport mechanisms. These areas are identified as important regulatory sites, the investigation of which are timely and promises a high rate of progress towards the longterm goal.
| Miller, M D; Hersey, S J (1996) Differential effects of GTP gamma S on acid and pepsinogen secretion by permeable gastric glands. Am J Physiol 270:G962-8 |
| Hersey, S J; Sachs, G (1995) Gastric acid secretion. Physiol Rev 75:155-89 |
| Shin, J M; Kajimura, M; Arguello, J M et al. (1994) Biochemical identification of transmembrane segments of the Ca(2+)-ATPase of sarcoplasmic reticulum. J Biol Chem 269:22533-7 |
| Reuben, M; Rising, L; Prinz, C et al. (1994) Cloning and expression of the rabbit gastric CCK-A receptor. Biochim Biophys Acta 1219:321-7 |
| Besancon, M; Shin, J M; Mercier, F et al. (1993) Membrane topology and omeprazole labeling of the gastric H+,K(+)-adenosinetriphosphatase. Biochemistry 32:2345-55 |
| Tang, L H; Miller, M D; Goldenring, J R et al. (1993) Partial agonism by gastrin for a cholecystokinin receptor mediating pepsinogen secretion. Am J Physiol 265:G865-72 |
| Scott, D R; Helander, H F; Hersey, S J et al. (1993) The site of acid secretion in the mammalian parietal cell. Biochim Biophys Acta 1146:73-80 |
| Jackson, R T; Hersey, S J (1991) Interaction of cocaine with nasal mucosa. Arch Otolaryngol Head Neck Surg 117:975-9 |
| Hersey, S; Tang, L; Pohl, J et al. (1990) Pepsinogen secretion in vitro. Methods Enzymol 192:124-39 |
| Perez, A; Blissard, D; Sachs, G et al. (1989) Evidence for a chloride conductance in secretory membrane of parietal cells. Am J Physiol 256:G299-305 |
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