Modulation of 3H-prostaglandin E2 binding sites in the rabbit gastric mucosa.
The binding of 3H-prostaglandin E2 (PGE2) to rabbit gastric mucosa was investigated. Binding depended on incubation time, temperature and pH, and was saturable and reversible. Scatchard plot analysis revealed a single class of binding sites with a dissociation constant (Kd) of 5.33 +/- 0.21 nM and a maximum number of binding sites (Bmax) of 138.1 +/- 3.4 fmol/mg protein. PGE1 and 16,16-dimethyl PGE2 potently competed with 3H-PGE2 for the binding sites of gastric mucosa, whereas PGA2, PGF2 alpha, 6-keto PGF1 alpha and thromboxane B2 were less potent. The gastric mucosa prepared from the rabbits given indomethacin (5 mg/kg s.c. three times) showed a lower Kd (2.47 +/- 0.19 nM) for 3H-PGE2 than that from untreated one. Treatment with a PGE1 analog, misoprostol (320 micrograms/kg s.c. three times) lowered the Bmax to 74.1 +/- 2.4 fmol/mg protein without any significant effect on the Kd value. It is concluded that rabbit gastric mucosa has specific binding sites for 3H-PGE2 which may be modulated by the levels of PGs in vivo.
Tomoi
M
M
Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Matsuo
M
M
Ono
T
T
Shibayama
F
F
D015064:16,16-Dimethylprostaglandin E2 / Q000378:metabolism; D000527:Alprostadil / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015232:Dinoprostone / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D016595:Misoprostol; D011817:Rabbits; D013696:Temperature
D016595:Misoprostol; D000527:Alprostadil; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin