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Inhibition by anti‐inflammatory agents of contraction induced by epidermal growth factor‐urogastrone in isolated longitudinal smooth muscle strips from guinea‐pig stomach
Author(s) -
Itoh H.,
Muramatsu I.,
Patel P.,
Lederis K.,
Hollenberg M.D.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11710.x
Subject(s) - endocrinology , medicine , contraction (grammar) , epidermal growth factor , pharmacology , chemistry , receptor
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 > naproxen > ibuprofen > 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 μ m ), 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 μ m ) failed to cause significant inhibition. 5 Preincubation of preparations for 2 h with 1 μ m hydrocortisone, prednisolone or dexamethasone caused an inhibition of EGF‐URO‐induced contraction of approximately 50%. However, steroids lacking either a 17α‐hydroxyl (corticosterone) or an 1lβ‐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 μ m and was maximal at 1 μ m . Cycloheximide (10 μ m ) 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.