Stimulation of pepsinogen secretion in permeable isolated gastric glands

Rabbit isolated gastric glands were treated with digitonin so that stimulation of pepsinogen secretion could be studied in a permeable system. Criteria for permeabilization were the release of lactate dehydrogenase in response to digitonin as well as the finding that calcium stimulation and spermine inhibition required the presence of digitonin. Other evidence confirmed that digitonin directly permeabilized chief cells. Pepsinogen secretion was elicited from digitonin-treated gastric glands by a number of agents, including calcium, vanadate, cholecystokinin octapeptide (CCK-OP), 8-bromo-adenosine 3',5'-cyclic monophosphate, and forskolin. Spermine was found to inhibit secretion stimulated by each of these agents only in the presence of digitonin, suggesting an intracellular site of spermine action. We concluded that spermine inhibition of secretion could be used as a marker of secretion elicited from permeable chief cells. The ability to stimulate pepsinogen secretion by such agents as CCK-OP and forskolin suggests that stimulus-secretion coupling is virtually intact even in permeable chief cells. We felt that this preparation should offer unusual opportunities for investigating the mechanisms involved in the intracellular regulation and activation of pepsinogen secretion.