Amylin, released from the gastric fundus, stimulates somatostatin and thus inhibits histamine and acid secretion in mice.
OBJECTIVE
Amylin, a peptide that displays 50% homology with calcitonin gene-related peptide (CGRP), is colocalized with somatostatin in endocrine cells of the gastric fundus. The present study was designed to determine the mechanism of action of amylin on gastric exocrine and endocrine secretion.


METHODS
Acid secretion was measured in the isolated mouse stomach by titration. Somatostatin and histamine secretion were measured in rat fundic segments by radioimmunoassay.


RESULTS
In isolated mouse stomach, amylin caused a concentration-dependent decrease in acid secretion. In rat fundic segments, amylin and CGRP each caused a concentration-dependent increase in somatostatin and a decrease in histamine secretion. Changes in histamine secretion induced by amylin reflected changes in somatostatin secretion and could be abolished by addition of somatostatin antibody. Both the somatostatin and the histamine responses to amylin were abolished by the selective amylin antagonist AC187 but were unaffected by the CGRP antagonist CGRP8-37. In contrast, the responses to CGRP were abolished by CGRP8-37 but were unaffected by AC187. AC187 alone decreased somatostatin and increased histamine in fundic segments and increased acid secretion in isolated stomach, indicating that endogenous amylin participates in the regulation of gastric endocrine (somatostatin and histamine) and exocrine (acid) secretion.


CONCLUSIONS
In gastric fundus, release of amylin from somatostatin cells interacts with distinct amylin receptors to enhance somatostatin secretion via an autocrine pathway that leads to inhibition of histamine and acid secretion.
Zaki
Muhammad
M
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, USA.
Koduru
Shashi
S
McCuen
Robert
R
Vuyyuru
Lokesh
L
Schubert
Mitchell L
ML
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004338:Drug Combinations; D005744:Gastric Acid / Q000378:metabolism*; D005748:Gastric Fundus / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism*
D000682:Amyloid; D004338:Drug Combinations; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D010455:Peptides; C058636:calcitonin gene-related peptide (8-37); C087166:AC 187; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide