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  • Title: Contractile actions of epidermal growth factor-urogastrone in isolated smooth muscle preparations from guinea pig stomach: structure-activity relationships and comparison with the effects of human transforming growth factor-alpha.
    Author: Hollenberg MD, Muramatsu I, Itoh H, Patel P, Yang SG, Lederis K.
    Journal: J Pharmacol Exp Ther; 1989 Jan; 248(1):384-90. PubMed ID: 2783610.
    Abstract:
    In two distinct isolated guinea pig stomach smooth muscle preparations, we have studied the contractile effects of intact human epidermal growth factor-urogastrone (mEGF-URO) and murine epidermal growth factor-urogastrone (mEGF-URO), along with the actions of derivatives (hEGF-URO1-47; mEGF-URO1-47) lacking the C-terminal pentapeptide. The effects of these polypeptides were compared with the actions of human transforming growth factor-alpha (TGF-alpha). In the longitudinal muscle preparation, wherein the contractile actions of agonists were abolished by 1 microM indomethacin, the order of potency was: hEGF-URO = mEGF-URO greater than TGF-alpha greater than hEGF-URO1-47 greater than or equal to mEGF-URO1-47. In this longitudinal muscle preparation, reproducible contractions could be obtained by rinsing the preparation free of agonist and by maintaining intermittent dose intervals of 1 hr or more. In contrast, in the circular muscle preparation, all agonists elicited a contractile effect that was present in the presence of 1 microM indomethacin. In this indomethacin-treated preparation, when an intermittent dosing regimen was used, repeated exposure to either human or murine EGF-URO caused a persistent desensitization. However, in the indomethacin-treated circular muscle preparation, repeated exposure to TGF-alpha and hEGF-URO1-47 during an intermittent dosing schedule caused only a low degree of persistent desensitization. In the indomethacin-treated circular muscle preparation, the order of potency for the contractile effect was: TGF-alpha = hEGF-URO1-47 greater than or equal to hEGF-URO.(ABSTRACT TRUNCATED AT 250 WORDS)
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