Copresence of prostaglandin EP2 and EP3 receptors on gastric enterochromaffin-like cell carcinoid in African rodents.
OBJECTIVE
Prostaglandins (PGs) have important roles in the regulation of gastric acid secretion. The aim of this study was to examine the possible presence of PG receptors on the gastric enterochromaffin-like (ECL) carcinoid of Mastomys natalensis, which might be a useful model of normal ECL cells.


METHODS
A [3H]PGE2 binding experiment was performed by using the ECL tumor membrane, and intracellular signal transduction was studied in the cells. In addition, Northern blot analysis using EP2 and EP3 receptor complementary DNAs was conducted.


RESULTS
[3H]PGE2 specifically bound to the tumor cell membrane, and the binding was displaced by various PGs with a potency order of PGE1 = PGE2 > enprostil > PGF2 alpha. Although PGE1 and PGE2 stimulated 5'-cyclic adenosine monophosphate (cAMP) production, neither PGF2 alpha nor enprostil had any effect. On the other hand, all of PGE1, PGE2, PGF2 alpha, and enprostil attenuated the forskolin-induced cAMP production. Moreover, enprostil inhibited histamine release induced by forskolin. However, on pertussis toxin treatment, PGE2 paradoxically enhanced the forskolin-induced increase of cAMP production. Finally, the presence of EP2 and EP3 receptor messenger RNAs was confirmed by RNA blot analysis.


CONCLUSIONS
The ECL carcinoid tumor cells of Mastomys seem to possess two subtypes of PGE receptor: EP2 linked to cAMP production and EP3 coupled with inhibitory guanosine 5'-triphosphate-binding proteins mediating the inhibition of cAMP production.
Naribayashi-Inomoto
Y
Y
Department of Internal Medicine, Kobe University School of Medicine, Japan.
Ding
M
M
Nakata
H
H
Narumiya
S
S
Sugimoto
Y
Y
Honda
A
A
Ichikawa
A
A
Chiba
T
T
Kinoshita
Y
Y
D000818:Animals; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002276:Carcinoid Tumor; D002462:Cell Membrane / Q000737:chemistry; D005576:Colforsin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000096:biosynthesis; D015237:Dinoprost / Q000494:pharmacology; D016620:Enprostil / Q000494:pharmacology; D004759:Enterochromaffin Cells / Q000737:chemistry*; D005260:Female; D006636:Histamine Release; D066298:In Vitro Techniques; D008954:Models, Biological; D009115:Muridae; D011453:Prostaglandins / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000032:analysis*
D011453:Prostaglandins; D018078:Receptors, Prostaglandin E; D005576:Colforsin; D015237:Dinoprost; D000242:Cyclic AMP; D016620:Enprostil; D002118:Calcium