Control of gastric acid secretion in somatostatin receptor 2 deficient mice: shift from endocrine/paracrine to neurocrine pathways.
The gastrin-enterochromaffin-like (ECL) cell-parietal cell axis is known to play an important role in the regulation of gastric acid secretion. Somatostatin, acting on somatostatin receptor type 2 (SSTR(2)), interferes with this axis by suppressing the activity of the gastrin cells, ECL cells, and parietal cells. Surprisingly, however, freely fed SSTR(2) knockout mice seem to display normal circulating gastrin concentration and unchanged acid output. In the present study, we compared the control of acid secretion in these mutant mice with that in wild-type mice. In SSTR(2) knockout mice, the number of gastrin cells was unchanged; whereas the numbers of somatostatin cells were reduced in the antrum (-55%) and increased in the oxyntic mucosa (35%). The ECL cells displayed a reduced expression of histidine decarboxylase and vesicle monoamine transport type 2 (determined by immunohistochemistry), and an impaired transformation of the granules to secretory vesicles (determined by electron microscopic analysis), suggesting low activity of the ECL cells. These changes were accompanied by an increased expression of galanin receptor type 1 in the oxyntic mucosa. The parietal cells were found to respond to pentagastrin or to vagal stimulation (evoked by pylorus ligation) with increased acid production. In conclusion, the inhibitory galanin-galanin receptor type 1 pathway is up-regulated in the ECL cells, and the direct stimulatory action of gastrin and vagal excitation is enhanced on the parietal cells in SSTR(2) knockout mice. We suggest that there is a remodeling of the neuroendocrine mechanisms that regulate acid secretion in these mutant mice.
Zhao
Chun-Mei
CM
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7006, Trondheim, Norway. chun-mei.zhao@ntnu.no
Martinez
Vicente
V
Piqueras
Laura
L
Wang
Lixin
L
Taché
Yvette
Y
Chen
Duan
D
D000818:Animals; D002452:Cell Count; D004759:Enterochromaffin Cells / Q000378:metabolism* / Q000648:ultrastructure; D019004:Galanin / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009490:Neurosecretory Systems / Q000378:metabolism; D019899:Paracrine Communication / Q000502:physiology*; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000648:ultrastructure; D044088:Receptors, Galanin / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D044088:Receptors, Galanin; D017481:Receptors, Somatostatin; C493453:Slc18a2 protein, mouse; C492049:Sstr2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D019004:Galanin; D006640:Histidine Decarboxylase