Inhibition by anti-inflammatory agents of contraction induced by epidermal growth factor-urogastrone in isolated longitudinal smooth muscle strips from guinea-pig stomach.
1. Epidermal growth factor-urogastrone (EGF-URO) caused a concentration-dependent contractile response of longitudinal muscle strips from the gastric body of the guinea-pig stomach. The contractile response to EGF-URO was monophasic, with tension returning rapidly to baseline. Desensitization was evident in that further addition of EGF-URO to the organ bath did not cause a second contraction. 2. Preincubation with indomethacin, ibuprofen, naproxen and aspirin markedly inhibited the contractions induced by EGF-URO with an order of potency (indomethacin greater than naproxen greater than ibuprofen greater than aspirin) that reflected the ability of these agents to inhibit cyclo-oxygenase. 3. The data indicate that prostanoids mediate the action of EGF-URO in the longitudinal muscle preparation. 4. Auranofin (0.5 to 50 microM), a chrysotherapeutic agent with antiproliferative properties used for treating rheumatoid arthritis, also markedly inhibited the EGF-URO response; however, other gold-containing compounds (aurothioglucose or gold sodium thiomalate at 30 to 100 microM) failed to cause significant inhibition. 5. Preincubation of preparations for 2 h with 1 microM hydrocortisone, prednisolone or dexamethasone caused an inhibition of EGF-URO-induced contraction of approximately 50%. However, steroids lacking either a 17 alpha-hydroxyl (corticosterone) or an 11 beta-hydroxyl (cortisone, deoxycorticosterone, prednisone) substituent did not inhibit the contraction caused by EGF-URO. For hydrocortisone, the inhibitory effect was half-maximal at 0.2 microM and was maximal at 1 microM. Cycloheximide (10 microM) blocked the inhibitory action of hydrocortisone and potentiated the contractile action of EGF-URO. 6. The ability of a variety of steroidal and non-steroidal anti-inflammatory agents to interfere with the action of EGF-URO in a smooth muscle preparation suggests that these agents may also inhibit the action of EGF-URO mediated by prostanoids in other target tissues. 7. The data also point to a potential role for EGF-URO in regulating gastric motility.
Itoh
H
H
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Alberta, Canada.
Muramatsu
I
I
Patel
P
P
Lederis
K
K
Hollenberg
M D
MD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001310:Auranofin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006168:Guinea Pigs; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009288:Naproxen / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013256:Steroids; D001310:Auranofin; D009288:Naproxen; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D003513:Cycloheximide; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin