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Endogenous Gastric Mediators: Patho‐Physiological Role and Measurements
Publication Name:
Current Protocols in Toxicology
Unit Number:
Unit 21.6
DOI:
10.1002/0471140856.tx2106s45
Online Posting Date:
August, 2010
Abstract
The protocols described in this unit are designed to present the major endogenous gastric mediators involved in the control of gastric acid secretion, namely gastrin and histamine, and in the regulation of gastric motility, which include motilin and ghrelin, under physiological and pathological conditions. The measurement of these mediators in plasma or serum of humans and animals by radioimmunoassay are described and their pathophysiological role is discussed. Curr. Protoc. Toxicol. 45:21.6.1-21.6.24. © 2010 by John Wiley & Sons, Inc.
Keywords: gastrin; histamine; motilin; ghrelin; stomach
Materials
Basic Protocol 1: Measurement of Gastrin Materials
Basic Protocol 2: Measurement of Histamine Materials
NOTE: All above reagents are ready to use except the acylation reagent, which is supplied as a concentrated solution and equalizing reagent is supplied lyophilized, to be reconstituted with distilled water. The histamine RIA kit contains materials for 100 quantitative determinations (including the standards) of histamine.
NOTE: For safety measures and basic radioprotection rules, see
CAUTION: The reagents should be stored at 2° to 8°C. Avoid microbiological contamination of the reagents. Do not use components beyond the expiration date shown on the kit labels. Do not mix various lots of any kit component within an individual assay. Inappropriate handling of the test samples or deviations from the test instructions can affect the result. Basic Protocol 3: Measurement of Motilin Materials
NOTE: The standard size of the RIA kit is sufficient for 125 RIA tubes. The Basic Protocol 4: Measurement of Ghrelin Materials
NOTE: The standard size of the kit is sufficient for 125 RIA tubes. The
NOTE: See
CAUTION: Due to the short half-life of iodine-125 (the tracer used with this kit), it is highly recommended to use the kit as soon as possible after receiving. All solutions should be used on the same day of rehydration. Never store reconstituted kit components as they are unstable. Use of stored reconstituted kit components to perform RIA may yield poor and unacceptable results. When using the ghrelin (human) RIA kit (Phoenix Pharmaceuticals), carefully follow the procedure for utilization of the RIA as described in “General protocol for radio immunoassay kit of peptides”. |
Figures
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Figure 21.6.1 Major luminal and mucosal endocrine (gastrin), paracrine (somatostatin), and neurocrine (GRP, acetylcholine) substances involved in the control of gastric acid secretion. Infection with H. pylori may stimulate gastric acid secretion by inhibiting the D-cell activity or inhibits this secretion by direct impairment of the parietal cells. -
Figure 21.6.2 Neuro-hormonal mechanisms involved in gastric acid secretion during cephalic and gastric phase of gastric acid secretion. -
Figure 21.6.3 Parietal cell with the receptors and intracellular stimulants of its proton pumps activated by histamine (through H2-receptors), Ach (through M3-receptors), and gastrin (through CCK2-receptors). Intracellular mediators of these stimulants are cAMP and Ca 2+ , which activate the protein-kinases resulting in the activation and recruitment of the proton pumps into the intracellular canalicular membrane. -
Figure 21.6.4 Hypergastrinemia, accompanying infection with H. pylori or treatment with potent gastric acid inhibitors, results in growth promotion of the oxyntic mucosa and gastric timorous tissue. -
Figure 21.6.5 Gastric infection with H. pylori and accompanying changes in the release of gastrin, somatostatin, and histamine with subsequent alteration in gastric acid secretion. -
Figure 21.6.6 Cellular and organ regulations of gastric acid secretion by the parietal cells with indication of their receptors and intracellular mediators (A) as well as various gastric substances controlling the activity of the G-cell, D-cells, ECL-cells, and parietal cells (B). -
Figure 21.6.7 Similarities between the amino acid sequence of ghrelin and motilin.
Videos
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