Discussion: Parietal Cell Secretory Regulation

The maladies of gastric secretion, including peptic ulcer disease, gastritis, and esophageal reflux, represent common and pervasive disorders throughout our population. Investigations during the past two decades have led to remarkable and profound changes in the treatment of acid-peptic disorders. Medical treatments have evolved from gastric resection through the evolution of "physiological" and selectively ablative techniques of vagal denervation. Currently, pharmacological remedies dominate the approach to ulcer disease, gastritis, and esophageal reflux. This evolution in less invasive treatment modalities has developed attendant on a greater understanding of the integrative and cellular physiology of gastric secretion. Nevertheless, while these research initiatives have led to impressive knowledge of cell surface pharmacology of the parietal cell, relatively little characterization of the intracellular mechanisms responsible for stimulation of acid secretion has occurred. Even less is known of the coordinated integrative mechanisms which function to maintain the normal homeostasis of the gastric mucosa. The research described in this section details progress in four areas of relevant gastric mucosal physiology: (1) the neurohormonal regulation of acid secretion, (2) the receptor-dependent regulation of histamine-stimulated acid secretion, (3) the complex mechanisms of second messenger activation mediating acid secretion, and (4) the intricacies of intracellular membrane dynamics within the parietal cell. Each of these areas promises to be a fertile field for future progress in understanding the physiology of gastric secretion.