Histamine secretion from rat enterochromaffinlike cells.
BACKGROUND
In vivo studies have suggested an important role for gastric enterochromaffinlike (ECL) cells in mediating acid secretion. Direct evidence for this function is lacking and requires a preparation of highly purified ECL cells. This work investigates the possible role and mechanism of histamine release from the ECL cell in the peripheral regulation of acid secretion, using purified ECL cells from rat fundic mucosa.


METHODS
A combination of elutriation and density-gradient centrifugation was used to purify rat fundic ECL cells. Enrichment was determined by the presence of acidic vacuoles containing a V type adenosine triphosphatase, electron microscopy, immunostaining, and histamine content and release.


RESULTS
ECL cells were enriched at least 65-fold with respect to the fundic epithelium. Gastrin (EC50 0.2 nmol/L) and cholecystokinin octapeptide (nonsulfated, EC50 0.04 nmol/L) stimulated histamine release in a time- and dose-dependent manner, suggesting a CCK-B receptor subtype, confirmed by the inhibition of gastrin/CCK stimulation with the CCK-B antagonist L365,260. Somatostatin also inhibited gastrin-mediated histamine release. Single cell imaging showed that gastrin elevated intracellular cytosolic calcium concentration biphasically. Carbachol and the C kinase activator 120-tetradecanoylphorbol-13-acetate also stimulated histamine release. Epinephrine (blocked by propranolol), forskolin, and dibutyryl-5'-cyclic adenosine monophosphate were also effective, implicating a beta-adrenergic pathway. The H3 agonist R-alpha-methyl-histamine inhibited, whereas the H3-antagonist thioperamide potentiated gastrin/CCK stimulated histamine release.


CONCLUSIONS
These in vitro results support a central role for the ECL cell in the peripheral regulation of gastric acid secretion.
Prinz
C
C
Department of Physiology and Medicine, University of California, Los Angeles.
Kajimura
M
M
Scott
D R
DR
Mercier
F
F
Helander
H F
HF
Sachs
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004759:Enterochromaffin Cells / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005755:Gastrins / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013268:Stimulation, Chemical
D005755:Gastrins; D011968:Receptors, Histamine; D013004:Somatostatin; D012844:Sincalide; D002118:Calcium