P2 purinergic receptor regulation of mucus glycoprotein secretion by rabbit gastric mucous cells in a primary culture.
OBJECTIVE
Physiological regulation of gastric mucus secretion has not been well studied. The present study investigated the effects of adenosine 5'-triphosphate (ATP), a P2 purinergic receptor agonist, and its analogues on gastric mucus secretion using gastric mucous cells in a primary culture.


METHODS
A monolayer culture of gastric mucous cells from adult rabbits were prepared after enzyme digestion. Mucus secretion was estimated from the release of [3H]glucosamine from prelabeled cells. Intracellular calcium concentration ([Ca2+]i) was monitored by a Ca(2+)-sensitive probe, indo-1. Prostaglandin E2 (PGE2) in the media was measured by an enzyme-linked immunoassay.


RESULTS
ATP significantly stimulated mucus secretion by these cells at nontoxic doses in a dose-dependent fashion. The order of potency of ATP analogues stimulating mucus secretion was alpha beta-methylene ATP > ATP > 2-methylthio ATP, whereas adenosine, a P1 purinergic receptor agonist, had no effect. ATP also induced an elevation of [Ca2+]i in a dose-dependent fashion. The efficacy of ATP analogues to increase [Ca2+]i showed a similar potency to their actions on mucus secretion. ATP increased PGE2 at relatively higher concentrations, whereas indomethacin did not block ATP-induced increase of mucus secretion.


CONCLUSIONS
These results suggest that ATP stimulates mucus secretion by gastric mucous cells through P2 purinergic receptors; this appears to be mediated by intracellular calcium not by endogenous PGE2.
Ota
S
S
Second Department of Internal Medicine, University of Tokyo, Japan.
Yoshiura
K
K
Takahashi
M
M
Hata
Y
Y
Kohmoto
O
O
Kawabe
T
T
Shimada
T
T
Hiraishi
H
H
Mutoh
H
H
Terano
A
A
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009093:Mucus / Q000378:metabolism; D009994:Osmolar Concentration; D011817:Rabbits; D011983:Receptors, Purinergic / Q000502:physiology*; D013997:Time Factors
D006023:Glycoproteins; D011983:Receptors, Purinergic; C047874:gastric mucus glycoproteins; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium