Peptone stimulates CCK-releasing peptide secretion by activating intestinal submucosal cholinergic neurons.

Abstract

In this study we tested the hypothesis that peptone in the intestine stimulates the secretion of the CCK-releasing peptide (CCK-RP) which mediates CCK secretion, and examined the enteric neural circuitry responsible for CCK-RP secretion. We used a "donor-recipient" rat intestinal perfusion model to quantify the CCK-RP secreted in response to nutrient stimulation. Infusion of concentrated intestinal perfusate collected from donor rat perfused with 5% peptone caused a 62 Ϯ 10% increase in protein secretion and an elevation of plasma CCK levels to 6.9 Ϯ 1.8 pM in the recipient rat. The stimulatory effect of the intestinal washings was abolished when the donor rats were pretreated with atropine or hexamethonium but not with guanethidine or vagotomy. Mucosal application of lidocaine but not serosal application of benzalkonium chloride which ablates the myenteric neurons in the donor rats also abolished the stimulatory action of the intestinal washings. Furthermore, treatment of the donor rats with a 5HT 3 antagonist and a substance P antagonist also prevented the secretion of CCK-RP. These observations suggest that peptone in the duodenum stimulates serotonin release which activates the sensory substance P neurons in the submucous plexus. Signals are then transmitted to cholinergic interneurons and to epithelial CCK-RP containing cells via cholinergic secretomotor neurons. This enteric neural circuitry which is responsible for the secretion of CCK-RP may in turn play an important role in the postprandial release of CCK. (

Diazepam-binding inhibitor mediates feedback regulation of pancreatic secretion and postprandial release of cholecystokinin

“…After a 5-hour diversion of bile-pancreatic juice, infusion of peptone resulted in a 5-fold increase in luminal DBI immunoreactivity. These data are consistent with our previous observation that peptone in the duodenum acts by stimulating the luminal secretion of CCK-RP, which in turn stimulates CCK release (9,14). DBI immunostaining and in situ hybridization studies in the rat confirmed that it is widely distributed in the villi of the upper intestine (22).…”

“…Pancreatic protein outputs were compared using ANOVA (total degrees of freedom, 71; F = 267.03; *P < 0.01). Plasma CCK levels were compared using Student's t test, *P < 0.01. and have shown that after a 5-hour diversion of bile-pancreatic juice, the intestinal perfusates collected from the donor rat did not contain significant amounts of CCK-RP (9). This is consistent with our current observation: after a 5-hour diversion of bile-pancreatic juice, luminal DBI immunoreactivity fell to basal levels and plasma CCK fell to 0.6 pM.…”

“…In a separate group of rats, perfusates were obtained after a 2-hour and a 5-hour diversion of bile-pancreatic juice. In previous studies, we used the donor-recipient rat model to demonstrate that peptone and oleic acid stimulate pancreatic protein secretion and CCK release in a manner that parallels the changes in luminal CCK-RP levels (9,14). To demonstrate that nutrient stimulates DBI secretion, 5% peptone was perfused for 1 hour after a 5-hour diversion of bile-pancreatic juice when plasma CCK concentrations had returned to basal levels.…”

“…However, dietary protein in the intestine competes for trypsin and prevents protease-induced feedback inhibition of CCK release. The resulting increase of active CCK-RP induces the release of CCK and stimulates pancreatic enzyme secretion, which has been proposed to be the major mechanism by which intact proteins stimulate CCK release in rats (9). To further evaluate if proteins such as casein in the intestine could prevent the inactivation of DBI 33-50 by proteases, we investigated the action of DBI 33-50 in the presence of casein in a rat model without bile-pancreatic juice diversion.…”

Identification of a protein hydrolysate responsive G protein-coupled receptor in enterocytes

“…The indirect involvement of G proteincoupled receptors (GPCRs) in these sensing events in which the release of their ligands is directly induced by luminal nutrients is well characterized. For example, free fatty acids directly induce the release of peptide YY (3), which in turn activates neuropeptide Y (NPY) receptors, or protein hydrolysate induces the release of CCK (12,42,48), which in turn activates the receptor CCK 1 R (63). The role of GPCRs as sensors that can directly respond to changes in luminal contents is not well defined.…”