The small intestine actively secretes HCO-3 and actively reabsorbs HCO-3 (or secretes H+). These processes are important in the normal function of the small intestine and in pathophysiological circumstances such as diarrhea. Nevertheless, the underlying ion transport events are unresolved and the intercellular and extracellular control mechanisms are not known. Moreover, the transporting cells responsible have not been identified. A subpopulation of mucosal cells in the jejunum of the urodele (Amphiuma) has been found to contain acid vesicles when exposed to the fluorescent stain acridine orange (AO). pH and K+ sensitive microelectrodes will be employed to measure the ion content of the vesicles and cytoplasm of the secretory cells of in vitro intestinal segments. Hypotheses regarding the cellular mechanisms of acid secretion will be tested. Scanning and transmission electron microscopy will be used along with AO flurosescence to determine the morphology of the secretory cells and their associated vesicles and to distinguish whether the changes in acid secretion result from changes in acid storage of H+ transport. The identity of the cells responsible for the enhanced acid secretion caused by catecholamines such as epinephrine will be determine and the ion transport events induced by catecholamines including, apparently, Na-H exchange studied in detail. The effect of cholinergic agents to reduce acid secretion will be examined. The ability of cholinergic agonists to stimulate HCO-3 secretion in the duodenum and adrenergic agents to block the effect will be documented using the pH stat technique. The effect of these agents on Na and C1 transport will be determined. The possibility that methacholine acts through elevation of cyclic AMP will be examined. These studies will provide the first electrophysiological and morphological analysis of an identified acid secretory cell in the intestinal mucosa. Whether the catecholamine-driven acid secretion is from the same or a different cell will be determined. The ion transport mechanisms responsible for spontaneous and epinephrine-stimulated acid secretion will be determined.
