Inhibition by anti‐inflammatory agents of contraction induced by epidermal growth factor‐urogastrone in isolated longitudinal smooth muscle strips from guinea‐pig stomach

Abstract

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 50juM), 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 pM) failed to cause significant inhibition. 5 Preincubation of preparations for 2 h with 1 JM hydrocortisone, prednisolone or dexamethasone caused an inhibition of EGF-URO-induced contraction of approximately 50%. However, steroids lacking either a 17x-hydroxyl (corticosterone) or an 1lI-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 JM and was maximal at 1 pM. Cycloheximide (1O gM) 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.

Detection of functional receptors for the proteinase-activated-receptor-2-activating polypeptide, SLIGRL-NH2, in rat vascular and gastric smooth muscle

“…1E). The concentrations of GS and Indo used were the maximal inhibitory concentrations of these two inhibitors in the gastric LM assay, as determined by concentration -inhibition curves obtained in previous work by us (Itoh et al 1988;Hollenberg 1994;Yang et id. 1993).…”

PKCα Deficiency in Mice Is Associated with Pulmonary Vascular Hyperresponsiveness to Thromboxane A2 and Increased Thromboxane Receptor Expression

“…However, compensative modulation of pulmonary vascular function by PKCι in PKCα -/- mice is unlikely, since pulmonary vascular hyperresponsiveness to U46619 was not reduced in PKCα -/- lungs following PKCι inhibition, as shown in this study. In line with this notion, it has been reported that treatment with the PKCι inhibitor sodium aurothiomalate failed to inhibit adrenaline-induced constriction of rat anterior mesenteric artery and vein [50] as well as epidermal growth factor-urogastrone-evoked contraction in isolated longitudinal smooth muscle strips from guinea-pig stomach [51]. Nevertheless, to our knowledge, this is the first report on the effects of selective PKCι inhibition on pulmonary vasoconstriction focusing on the specific response to U46619 in PKCα -/- lungs, so a potential PKCι-mediated modulation of pulmonary vascular function needs to be further evaluated in future studies.…”

Synergistic actions of epidermal growth factor‐urogastrone and vasopressin in cultured aortic A‐10 smooth muscle cells

“…Additionally, EGF-URO is known to exhibit a number of other biological activities, ranging from the stimulation of cellular calcium flux (Sawyer and Cohen, 1981) t o the modulation of smooth muscle contractility (Muramatsu et al, 1985Gan et al, 1990). In our own work, focused on the action in vitro of EGF-URO in smooth muscle systems, we have observed that in some preparations, derived from both vascular and non-vascular tissues, the contractile action of EGF-URO is entirely due to the production of prostanoids (Muramatsu et al, 1985Itoh et al, 1988;Pate1 et al, 1988). Thus, we have become interested to determine the mechanism(s) whereby EGF-URO stimulates the production of prostanoids in smooth muscle-derived cells; and we have turned our attention to focus on the effects of EGF-URO in smooth muscle-derived cell cultures.…”