Characterization of Receptors Regulating Secretory Function in the Fundic Mucosa

: A model for a present view of the major pathways and receptors mediating function in the canine fundic mucosa is depicted in Figure 1. Gastrin has direct actions on the parietal cell and on the somatostatin cell; action on the parietal cell, but not somatostatin cell, is potentiated by histamine. In contrast, gastrin action on the somatostatin cell is potentiated by beta-adrenergic agonists. The potency of H2 blockers against gastrin may reflect blockage by these inhibitors of the stimulatory (parietal cell), but not the inhibitory (somatostatin cell), component of gastrin action, thus shifting the balance of gastrin effects toward the inhibitory side. The profound effects of H2 antagonists on gastrin action may also reflect an effect mediated by histamine release, but this possibility awaits direct confirmation. Cholinergic pathways also have at least dual sites of action: stimulation of the parietal cell, and blockage of the release of the inhibitory transmitter somatostatin. Anticholinergic agents may therefore have a dual acid inhibitory effect by reducing direct parietal cell stimulation and enhancing somatostatin release. There is little doubt that this model will rapidly evolve, but the concept that the pathways mediating acid secretion both converge in parallel at the parietal cell, and act in series to cause the release of paracrine transmitters, is attractive and likely to persist.