Distinctive actions of epidermal growth factor-urogastrone in isolated smooth muscle preparations from guinea pig stomach: differential inhibition by indomethacin.
ABSTRACT Epidermal growth factor-urogastrone (murine EGF-URO) caused concentration-dependent contractile responses in preparations of longitudinal and circular smooth muscle derived from guinea pig stomach. The actions of EGF-URO in these two preparations were distinguished in terms of the ability of indomethacin to block EGF-URO-mediated contraction completely in the longitudinal muscle preparation but not in the circular muscle preparation. The EC50 for EGF-URO was 2 to 5 nM in the longitudinal muscle preparations and 20 to 50 nM in the indomethacin-treated circular muscle preparation. The action of EGF-URO in the longitudinal preparation also was inhibited by ibuprofen, aspirin and by anti-inflammatory steroids possessing an 11-beta-hydroxyl; the corresponding steroids lacking the 11-beta-hydroxyl substituent were inactive. In contrast, little or no effect of the anti-inflammatory steroids on the EGF-URO-mediated response was observed in the indomethacin-treated circular muscle preparation. Partial inhibition (about 30%) of the EGF-URO-mediated contraction of the indomethacin-sensitive longitudinal preparation was caused by mepacrine and p-bromophenyl-acylbromide, whereas esculetine, tranylcypromine, prazosin, yohimbine and cyproheptadine had no effect. The action of EGF-URO in both preparations exhibited marked tachyphyllaxis, which could not be attributed either to the production of inhibitory factors or to the disappearance of EGF-URO from the organ bath. The response of both preparations required the presence of extracellular calcium and was inhibited largely (90%, longitudinal preparation) or in part (69%, indomethacin-treated circular preparation) by verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
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ABSTRACT: Summary Increasing evidence indicates that epidermal growth factor and transforming growth factor-α are involved in the maintenance of oesophageal mucosal integrity. However, their cellular origin and the exact localization of their receptor in the oesophagus are still unclear. Therefore, we examined the expression of the two growth factors and their shared receptor in the normal human oesophagus at both mRNA and protein level, by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction. In addition to being expressed in the proliferative compartment of the oesophageal epithelium, the receptor was found in a variety of cells, including smooth muscle cells, submucosal gland cells and the epithelium lining their ducts. Immunohistochemically, the pattern of distribution of epidermal growth factor paralleled that of its receptor. In situ hybridization demonstrated epidermal growth factor mRNA expression in the oesophageal epithelium and submucosal glands. Additionally, amplified transcripts of predicted size were detected by reverse transcription-polymerase chain reaction, thus confirming that authentic transcripts of the growth factor exist in the normal human oesophagus. Transforming growth factor-α mRNA and protein expression, while similar to that of epidermal growth factor, predominated in the more differentiated cell layers of the stratified squamous epithelium. These results demonstrate that the normal oesophagus can synthesize both growth factors. Moreover, the peculiar distribution of these peptides and the concomitant expression of their receptor in multiple cell types suggest that the two growth factors may exert diverse physiological functions in the oesophagus and participate in defence and reparative events following mucosal injury.The Histochemical Journal 01/1997; 29(10):745-758.
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ABSTRACT: A model of gastric ulceration in the rat has been used to determine the expression of four messenger RNAs (mRNAs) encoding peptides considered to play active parts in the healing response. The trefoil peptides, rat spasmolytic polypeptide (rSP) and rat intestinal trefoil factor (rITF), along with epidermal growth factor (EFG) and transforming growth factor alpha (TGFα) were the molecules studied. Ulceration was caused under anaesthesia by brief application of a liquid nitrogen-filled cryoprobe to the gastric serosal surface and RNA expression was monitored over the next 10 days. Each mRNA was quantified by ribonuclease protection assay, and mRNAs encoding rSP and rITF were localized within tissue sections by hybridization in situ with 35S antisense riboprobes. Ulceration induced the very rapid expression of first rSP and then rITF mRNA, whereas the mRNAs encoding EGF and TGFα increased at later times, with maxima recorded at 3 and 6 days, respectively. Hybridization in situ detected extensive rSP mRNA expression in the regenerative epithelia. The pronounced, but temporally different patterns of mRNA induction after ulceration suggest that the trefoil peptides may fulfil different and more ummediate roles than the more ‘traditional’ healing proteins EGF and TGAα.The Journal of Pathology 03/1995; 175(4):405 - 414. · 7.59 Impact Factor
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ABSTRACT: Contractility of smooth muscle within mammalian urogenital organ systems has an established role in physiological/pathophysiological functioning of the component structures. Our aim was to examine the direct effect of epidermal growth factor (EGF) on smooth muscle tone as well as its indirect effects in regulatinga1-adrenoceptor-mediated contraction of the prostate, the vas deferens and renal arteries. Tissues were mounted isometrically, under controlled conditions, and changes in tension in response to treatment with phenylephrine (PE) with or without pretreatment with EGF were recorded on a physiological recorder via force transducers. In the rabbit prostate, EGF potentiated the magnitude of contraction to PE. The potentiation appeared to be dependent on cyclo-oxygenase products. In the human prostate, EGF potentiated the contractile response to PE. EGF had no effect on the PE-induced contraction of the rabbit renal artery and vas deferens. EGF alone did not alter smooth muscle tone in any of the above-mentioned tissues. The main finding of this study is the difference in the regulation by EGF of thea1-adrenoceptor-mediated response in smooth muscle of the prostate, from that by the vas deferens and renal artery. The reasons for this difference in response remain to be elucidated. This study may form the basis for further investigation into receptor transregulation and its relevance to symptomatic benign prostatic hyperplasia (BPH).Urological Research 01/1997; 25. · 1.59 Impact Factor