Gap junctional channels regulate acid secretion in the mammalian gastric gland.
Gap junction channels are regarded as a primary pathway for intercellular message transfer, including calcium wave propagation. Our study identified two gap junctional proteins, connexin26 and connexin32, in rat gastric glands by RT-PCR, Western blot analysis, and immunofluorescence. We demonstrated a potential physiological role of the gap junctional channels in the acid secretory process using the calcium indicator fluo-3, and microinjection of Lucifer Yellow. Application of gastrin (10-7 m) to the basolateral membrane resulted in the induction of uniphasic calcium signals in adjacent parietal cells. In addition, single parietal cell microinjections in intact glands with the cell-impermeant dye Lucifer Yellow resulted in a transfer of dye from the injected cell to the adjacent parietal cell following gastrin stimulation, demonstrating gastrin-induced cell-to-cell communication. Both calcium wave propagation and Lucifer Yellow transfer were blocked by the gap junction inhibitor 18alpha-glycyrrhetinic acid. Our studies demonstrate that functional gap junction channels in gastric glands provide an effective means for rapid cell-to-cell communication and allow for the rapid onset of acid secretion.
Radebold
K
K
Department of Surgery, Yale University School of Medicine, BML 263, 310 Cedar St., New Haven, CT 06510, USA.
Horakova
E
E
Gloeckner
J
J
Ortega
G
G
Spray
D C
DC
Vieweger
H
H
Siebert
K
K
Manuelidis
L
L
Geibel
J P
JP
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D000072259:Connexin 26; D017630:Connexins / Q000032:analysis / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D007546:Isoquinolines / Q000737:chemistry; D008322:Mammals; D008845:Microinjections / Q000379:methods; D008856:Microscopy, Fluorescence; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097002:Gap Junction beta-1 Protein
D002118:Calcium; D000072259:Connexin 26; D017630:Connexins; D007546:Isoquinolines; D000097002:Gap Junction beta-1 Protein; C017475:lucifer yellow