Laboratory  of  John G. Forte

Department of Cell & Molecular Biology,  University of California, Berkeley
 
  GASTROENTEROLOGY, Vol. 73(4 pt 2):941-55, Oct 1977
 

Ultrastructural changes in oxyntic cells associated with secretory function: a membrane-recycling hypothesis

  
  Trudy M. Forte, Terry E. Machen, and John G. Forte
Donner Laboratory and Department of Physiology-Anatomy, University of California, Berkeley, California 		 
Abstract: Morphological changes accompanying stimulation of acid secretion in oxyntic cells of various animals is now well documented. The major ultrastructural observation is that active secretion is paralleled by an increase of secretory plasma membrane area and a decrease in the cytoplasmic smooth membrane components. These qualitative observations have been corroborated by stereological studies of Helander and Hirschowitz on the dog oxyntic cell, which indicate that at maximal stimulation there is a 10-fold increase in surface membrane density together with a 50% decrease in cytoplasmic tubulovesicles. Similar results were obtained for frog and mouse oxyntic cells. These earlier studies on qualitative and quantitative changes of membrane components associated with the process of HCl secretion were primarily carried out under steady state conditions, that is, in the nonsecreting phase (either before stimulation or after removal of stimulus) and in the maximally secreting phase. In the present ultrastructural study, we have assessed the time course of events which occur in piglet gastric mucosa after the addition of histamine as well as after removal of the secretagogue. Early time points after the onset of acid secretion of the return of cells to the resting phase reveal interesting ultrastructural changes normally not seen in the steady state condition.



Excerpt from Discussion: Addition of secretagogue triggers a series of events which within relatively short time spans (3 to 4 min) result in an apparent elaboration of secretory surface. Tubulovesicles migrate to the secretory surface, fuse, and are incorporated into it, thus increasing surface area. Microfilaments and microtubules appear to contribute to this process and may play an essential role in translocation of cytoplasmic membranes to the surface, as well as in mobility and form of the secretory surface itself. At maximal secretion, many microfilaments are detached and centrally located, where they may serve as important cytoskeletal structures, reinforcing the architecture of the elongated microvilli. Upon removal of the secretagogue, the microfilaments are disoriented, thus accounting for the rapid appearance (within 7 min) of condensed canaliculi. The elaborate secretory membranes fold upon one another and adjacent outer membrane leaflets are in close contact forming pentalaminar membrane configurations. These pentalaminar structures are endocytosed into the cell in a massive reversal of membrane flow.


  JOURNAL OF BIOLOGICAL CHEMISTRY, Vol. 256(7):3149-52, Apr 1981
 

Changes in the membrane environment of the (K++ H+)-ATPase following stimulation of the gastric oxyntic cell

  
  J. Mario Wolosin and John G. Forte
Department of Physiology-Anatomy, University of California, Berkeley, California 		 
Abstract: Biochemical evidence is presented for changes in the membrane environment of the (K++H+)-dependent ATPase enzyme of the oxyntic cell following in vivo gastric stimulation of young New Zealand rabbits. The changes are inferred from the marked differences in the sedimentation properties of the (K++H+)-ATPase when obtained from homogenates of either stimulated or nonstimulated (resting) fundic gastric epithelium. Stimulation resulted in a redistribution of K+-ATPase activity that was reduced to less than half in the microsomal pellet and concomitantly increased in the membrane fractions normally associated with nuclei and mitochondria. Density gradient fractionation of the mitochondrial pellet yield a preparation rich in (K++H+)-ATPase. Our studies indicated that the membranes in this preparation are far larger and apparently denser than the microsomal vesicles associated with the nonstimulated state of the cell. The specific nature of the relationship between stimulation and the observed changes is suggested by the lack of change in the distribution of enzymatic activities unrelated to the apical pole of the oxyntic cell. Preliminary, tentative information aimed at identifying the processes responsible for the observed changes is presented.