Inhibition of acid formation in rabbit parietal cells by prostaglandins is mediated by the prostaglandin E2 receptor.
The affinities of seven natural and synthetic prostaglandins [PGE2; 16,16-dimethyl PGE2; iloprost (stable prostacyclin analogue); PGF2 alpha; PGD2; BW245c (stable PGD2 analogue); and U46619 (stable thromboxane analogue)] to the PGE2 binding site of rabbit gastric mucosa were determined by measuring [3H]PGE2 displacement from its high-affinity plasma membrane binding sites. In parallel, the potency of each prostaglandin in inhibiting acid generation in vitro was determined by measuring the inhibition of histamine-stimulated [14C]aminopyrine accumulation in rabbit parietal cells prepared by enzymatic dispersion and enriched by counterflow elutriation. All seven prostaglandins displaced [3H]PGE2 and inhibited histamine-stimulated [14C]aminopyrine accumulation in a concentration-dependent manner. For all tested prostaglandins, the IC50 values were in excellent agreement for both variables measured. It is concluded that (a) a PGE2 receptor is localized on the parietal cell and mediates inhibition of acid formation by all prostaglandins and (b) the different in vitro antisecretory potencies of prostaglandins can be attributed to their different affinities to this PGE2 receptor.
Seidler
U
U
Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Federal Republic of Germany.
Beinborn
M
M
Sewing
K F
KF
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015232:Dinoprostone / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000502:physiology*; D018078:Receptors, Prostaglandin E
D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D000632:Aminopyrine; D006632:Histamine; D015232:Dinoprostone