Gastric acid secretion contributes to ulcer formation and its control is one of the primary targets of pharmacologic agents employed to promote ulcer healing. Thus, a more thorough understanding of the cellular and molecular mechanisms which control acid secretion will be extremely valuable in future efforts to explain ulcer pathogenesis and treat ulcer pathology. The cytoplasmic tail of the H,K-ATPase n-subunit possesses a tyrosine-based endocytosis motif which is necessary for the re-internalization of the holoenzyme and therefore contributes to the cessation of gastric acid secretion in transgenic animals. However, the mechanism through which this endocytosis signal is silenced to permit prolonged acid secretion during gastric stimulation has yet to be determined. It is proposed that the cytoskeleton that underlies the apical secretory canalicular membrane prevents the Is-subunit's constitutive endocytosis signal from mediating the holoenzyme's internalization. With the utilization of transgenic mice, the role of identified molecular domains in the H,K-ATPase in regulating gastric acid secretion may be elucidated.
NIH ExPorter
NIH ExPorter