The cellular localization of the cholecystokinin 2 (gastrin) receptor in the stomach.
The role of the gastric acid secretagogues acetylcholine, gastrin and histamine has been debated for decades. Initially, the mast cell was considered the source of acid stimulatory histamine. Later, Håkanson & Owman (1969) showed that the entero-chromaffinlike (ECL) cell produces and stores histamine in several species, including rat and man. Kahlson et al. (1964) showed that food and gastrin stimulated oxyntic mucosal histamine synthesis and release, Berglindh et at. (1976) that histamine and cholinergics but not gastrin induced acid secretion in isolated oxyntic glands and parietal cells, and Rangachari (1995) that acetylcholine or gastrin released histamine in isolated mucosa. These findings suggested that gastrin stimulates acid secretion through release of ECL cell histamine. Studying simultaneous histamine release and acid secretion in isolated oxyntic mucosal cells, we found that gastrin stimulated acid secretion only in preparations releasing histamine. Moreover, in the isolated rat stomach, gastrin stimulated both histamine release and acid secretion. Maximal acid output was higher with histamine than with gastrin, and augmented by acetylcholine but not by gastrin. These findings strongly suggested that gastrin acts by releasing histamine. Finally, a fluorescein-labelled gastrin analogue bound to the ECL cell, not to the parietal or stem cell regions. This is interesting, recalling that gastrin has a potent and specific trophic effect on the ECL cell and only a general effect on all other oxyntic cell types. In conclusion, physiological observations are best explained by localising the CCK2 receptor only to the ECL cell, the other effects of gastrin on the gastric mucosa being secondary to the release of mediators from the ECL cell.
Waldum
Helge L
HL
Norwegian University of Science and Technology, Faculty of Medicine, Department of Intra-abdominal Diseases, Trondheim University Hospital, Trondheim, Norway. helge.waldum@medisin.ntnu.no
Kleveland
Per M
PM
Sandvik
Arne K
AK
Brenna
Eiliv
E
Syversen
Unni
U
Bakke
Ingunn
I
Tømmerås
Karin
K
D000818:Animals; D019861:Enterochromaffin-like Cells / Q000378:metabolism / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology
D011949:Receptors, Cholecystokinin