Interaction among Secretagogues on Pepsinogen Secretion from Rat Gastric Chief Cells.

Abstract

We examined the interaction among secretagogues that stimulate pepsinogen secretion through different pathways in vivo and in vitro. In in vitro study, a combined administration of secretin and carbachol or cholecystokinin octapeptide (CCK-8) to the culture medium of chief cells potentiated pepsinogen secretion. Moreover, the response induced by carbachol or CCK-8 with forskolin was greater than that with secretin. We examined the interaction among receptor-related second mediators, and found that carbachol- or CCK-8-induced intracellular Ca2+ concentration ([Ca2+]i) increase was not affected by secretin or forskolin. Both these substances, however, significantly reduced secretin-induced cAMP production. On the contrary, CCK-8 significantly increased forskolin-induced cAMP production, while carbachol increased it slightly. Calcium ionophore, A23187, or protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), did not alter secretin- or forskolin-induced cellular cAMP production; and the reductive effect of carbachol or CCK-8 on secretin-induced cAMP production was restored by their competitive antagonists, atropine or lorglumide. EC50 of those antagonists was almost the same value as IC50 on pepsinogen secretion and [Ca2+]i increase. These results indicate that secretin-induced cAMP production is interfered with by receptor related agonists like CCK-8 and carbachol. It may be suggested that there is a kind of "cross-talk," between the adenylate cyclase system, that is, the secretin receptor, and carbachol or CCK-8 receptor. The interactions between secretin and other secretagogues (carbachol, CCK-8, tetragastrin and histamine) were examined using the perfused rat stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

Secretin regulates paracellular permeability in canine gastric monolayers by a Src kinase-dependent pathway

“…The potency of secretin for altering TER in these gastric epithelial monolayers indicates activation at a specific secretin receptor. Indirect evidence supports the existence of functional secretin receptors on gastric chief and mucous cells, but not parietal cells (11,20,25,28). To date, only one secretin receptor has been cloned and characterized (34).…”

“…Secretin has well-defined effects on chief cells, stimulating pepsinogen secretion by canine chief cells, rat gastric glands, and purified guinea pig chief cells in vitro (20,25,28). Because chief cells are the major component of canine gastric epithelial monolayer cultures (3) and secretin induces pepsinogen release from these cultures (25), secretin is a candidate to regulate other actions in these gastric cells.…”

Motilin stimulates pepsinogen secretion in Suncus murinus

“…Pepsinogen is secreted in response to a meal but also occurs during the interdigestive state [2]. In vivo and in vitro studies on pepsinogen secretion have demonstrated that acetylcholine and cholinergic agents stimulate pepsinogen secretion and this response is inhibited by cholinergic antagonists [3,4], suggesting that muscarinic cholinergic receptors are directly and strongly associated with the stimulation of chief cells for pepsinogen secretion [1]. In addition, pepsinogen secretion appears to be regulated by several hormones.…”