Source: UNIV OF CALIFORNIA (VET-MED) submitted to
SST2 RECEPTORS AND REGULATION OF GASTRIC SECRETIONS
Sponsoring Institution
Cooperating Schools of Veterinary Medicine
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0194704
Grant No.
(N/A)
Project No.
CALV-NIH01-CA89140
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
May 15, 2001
Project End Date
Mar 31, 2004
Grant Year
(N/A)
Project Director
Lloyd, K. C.
Recipient Organization
UNIV OF CALIFORNIA (VET-MED)
(N/A)
DAVIS,CA 95616
Performing Department
ANATOMY, PHYSIOLOGY AND CELL BIOLOGY
Non Technical Summary
Food ingestion evokes multiple stimulatory and inhibitory factors that provide levels of acidification of gastric contents suitable for digestion and protection against pathogens while preventing the damaging actions of acid on upper GI mucosa. Conclusions from these studies will lead to a more thorough understanding of how dietary nutrients elicit physiological regulation over gastric acid secretion.
Animal Health Component
25%
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3053840101033%
3053840102033%
3053840103034%
Goals / Objectives
We propose to study the pathway and mediators of the efferent limb of the enterogastric reflex. This project will determine the physiological role of ss2 receptors in enterogastric inhibition of gastric acid secretion.
Project Methods
The central hypothesis for our project is that the efferent limb of the enterogastric reflex is mediated by somatostatin-induced activation of ss2 receptors on gastric G and ECL cells. We will test this hypothesis by determining the extent to which somatostatin activation of sst2 receptors in vivo mediates enterogastric regulation of gastric acid secretion, identifying the cell types involved in the efferent limb of the enterogastric reflex and defining the role of the neural innervation of the stomach in the enterogastric reflex.

Progress 05/15/01 to 03/31/04

Outputs
This is a 3 year project to determine the physiological role of sst2 receptors in enterogastric inhibition of meal-stimulated gastric acid secretion. The central hypothesis to be tested is that the efferent limb of the enterogastric reflex is mediated by somatostatin-induced activation of sst2 receptors on gastric G and ECL cells. Three specific aims were originally included in the proposal. These studies have all continued to support our hypothesis that somatostatin type 2 receptors are a major effector of enterogastric inhibition of meal-stimulated gastric acid secretion. We conclude that this role is mediated through the efferent limb of the reflex.

Impacts
The outcome of these studies will be a better understanding of the regulation of gastric function by intestinal nutrients. These studies may also lead to improved therapies for gastric disorders, including peptic ulcer.

Publications

  • No publications reported this period


Progress 01/01/03 to 12/31/03

Outputs
This project continues to pursue examination of the hypothesis that sst2 receptors mediate enterogastric acid inhibition induced by dietary nutrients. Studies to date have shown that gastrin-mediate and non-gastrin mediated stimulation of gastric acid secretion are inhibited by all intestinal nutrients to varying degrees via sst2 receptors. These studies have been conducted in gastrin knockout mice and in sst2 receptor knockout mice.

Impacts
The outcome of these studies will be a better understanding of the regulation of gastric function by intestinal nutrients. These studies may also lead to improved therapies for gastric disorders, including peptic ulcer.

Publications

  • No publications reported this period


Progress 01/01/02 to 12/31/02

Outputs
This research intends to determine the physiological role of sst2 receptors in the regulation of gastric acid secretion stimulated by a meal. The gastric phase of secretion is the time of greatest acid secretion by the gastric parietal cell. Upon entry of chyme into the upper duodenum from the stomach, afferent signals are elicited from the intestine that cause inhibition of acid secretion. The efferent limb of this process is mediated by somatostatin. Our work utilizes knockout mice with specific deletions of the gastrin and somatostatin type 2 (sst2) receptor to elucidate the mechanism of acid inhibition. So far, we have determined that sst2 receptors mediate all of the inhibitory effect of dietary constituents entering the intestine. Our work continues to determine if this effect is mediate by an inhibition of meal-stimulated gastrin release, gastrin-stimulated histamine release, or both.

Impacts
Our work intends to better understand how the stomach turns on and turns off secretion of stomach acid. Experience tells us that upon eating, acid secretion by the stomach is turned on to aid digestion. What is not so obvious is that once the ingested meal moves through the stomach and into the intestine, acid secretion begins to wane and finally is turned off nearly completely. It is important to understand the mechanisms and pathways by which this stomach acid is ?turned off?, as stomach acid is an important component of the cause of ulcers, and further understanding how to turn stomach acid off will help not only in the development of better drugs but in more efficacious dietary recommendations.

Publications

  • No publications reported this period