|Budget Amount *help
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2000: ¥6,500,000 (Direct Cost: ¥6,500,000)
Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the peptide are present in rat stomach, but its cellular source has yet to be determined. Using two different antibodies against the N- and C-terminal regions of rat ghrelin, we identified ghrelin-producing cells in the gastrointestinal tracts of rats and humans by right and electron microscopic immunohistochemistry and in situ hybridization combined with immunohistochemistry. Ghrelin-immunoreactive cells, which are not enterochromaffin-like cells, D cells, or enterochromaffin cells, accounted for about 20% of the endocrine cell population in rat and human oxyntic glands. Rat ghrelin was present in round, compact, electron-dense granules compatible with those of X/A-like cells whose hormonal product and physiological functions have not previously been clarified. The loc
alization, population, and ultrastructural features of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cells. Ghrelin also was found in enteric endocrine cells of rats and humans. Using two RIAs for the N- and C-terminal regions of ghrelin, *** determined its content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fundus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findings provide clues to additional, as yet undefined, physiological functions of this novel gastrointestinal hormone.
Visceral sensory information is transmitted to the brain through the afferent vagus nerve. Ghrelin, a peptide primarily produced in the stomach, stimulates both feeding and growth hormone secretion from the pituitary. However, how stomach-derived ghrelin exerts these central actions is still unknown. Here we determined the role of the gastric afferent vagal nerve in ghrelin's functions.
Blockade of the gastric vagal afferent abolished ghrelin-induced feeding, growth hormone secretion, and activation of NPY-producing and GHRH-producing neurons. Ghrelin receptors were synthesized in vagal afferent neurons in the nodose ganglion and transported to the afferent terminals. Ghrelin suppressed firing of the vagal afferent, whereas CCK stimulated it. This study indicates that the gastric vagal afferent is the major pathway conveying ghrelin's signals for starvation and growth hormone secretion to the brain. Less