Effect of Urogastrone in the Zollinger-Ellison Syndrome

Elder, J. B.; Gillespie, Iain; Ganguli, P. C.; Delamore, W.I; Gregory, H.

doi:10.1016/s0140-6736(75)90842-9

Cited by 36 publications

(16 citation statements)

References 24 publications

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“…EGF is also reported to induce vasodilatation in a number of vascular beds (femoral, mesenteric, coronary, and renal) in anesthetized dogs and EGF (gg/kg) sheep (5,25,27). In clinical studies, partially purifed EGF extracted from human urine (urogastrone) was administered to modulate gastric acid secretion; no significant changes in cardiovascular parameters were described (18)(19)(20)(21). In addition to the vasoactive properties of EGF, a number of other nonmitogenic responses have been described, such as effects on plasma calcium concentrations (28,29) and inhibition of renin secretion (30).…”

Section: Discussionmentioning

confidence: 99%

“…The potential therapeutic effects of EGF have been of interest for a number of years. Partially purified EGF preparations extracted from human urine (referred to as urogastrone) have been administered to humans as early as the mid-1970s to modulate gastric acid secretion (18)(19)(20)(21). Using gene transfer techniques to deliver a gene encoding the secreted form of vascular endothelial cell growth factor, the first human study attempting to accelerate new blood vessel growth is ongoing (22), and studies exploring the therapeutic benefit of genes for basic fibroblast growth factor in animal models are underway (23).…”

mentioning

confidence: 99%

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Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

Keiser¹,

Ryan²

1996

Proc. Natl. Acad. Sci. U.S.A.

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The therapeutic application of growth factors to human disease has become closer to reality with the advent of faster means of synthesizing these molecules and novel drug delivery strategies. Epidermal growth factor (EGF) belongs to a large family of molecules with the ability to modulate growth. Purified extracts of EGF have been used clinically to modulate gastrointestinal secretion of hormones and accelerate healing. EGF is also reported to have both vascular smooth muscle contractile and relaxing activity. Cardiovascular studies were performed with the bioactive 48-amino acid fragment of human EGF in rodents and primates to determine the effects of EGF on blood pressure and heart rate in conscious animals. Intravenous infusion of EGF induced an initial pressor response in rats followed by a prolonged decrease in blood pressure. In contrast, in monkeys, EGF had dose-related blood pressure-lowering effects only; significant hypotension was observed at doses ranging from 3 to 300 ,lg/kg i.v. Hypotension was associated with modest tachycardia.in both species. To our knowledge, this is the first report of hemodynamic effects of EGF in primates, and it clearly documents that the mitogenic role of growth factors such as EGF is but one aspect of their physiology.In addition to the well-recognized mitogenic activity of growth factors, there is an increasing understanding of their vasoactive effects. Epidermal growth factor (EGF) belongs to a large family of molecules with the ability to modulate growth (1, 2). EGF is also reported to have both vascular smooth muscle contractile and relaxing activity in vitro (3-6). Berk et al. (4) reported that EGF produced contractions in isolated rat aorta that were roughly 40% of the maximal response to angiotensin; time to peak tension was relatively short (2-3 min). In contrast, Namiki and Akatsuka (7) reported that EGF relaxed isolated rat aortic strips; Muramatsu et al. (6) reported similar findings in isolated canine mesenteric arteries. Divergent results have also been obtained from in vivo studies. Gan et al. (8) reported that EGF had no effect on regional hemodynamics in anesthetized rats; however, regional bed vasodilatation was observed in the anesthetized dog (5). Thus, there is remarkable species heterogeneity in the vasoactive properties of EGF.A number of growth factors are receiving increased attention as potential therapeutic agents. EGF, hepatocyte growth factor, and insulin-like growth factor are reported to protect against or ameliorate renal ischemic injury in a variety of models (9-13), although these effects show some species variation (14). EGF is also reported to accelerate gastric ulcer healing and inhibit gastric acid secretion (15-17). The potential therapeutic effects of EGF have been of interest for a number of years. Partially purified EGF preparations extracted from human urine (referred to as urogastrone) have been administered to humans as early as the mid-1970s to modulate gastric acid secretion (18)(19)(20)(21). Using gene transfer techni...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

Keiser¹,

Ryan²

1996

Proc. Natl. Acad. Sci. U.S.A.

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“…It is common knowledge that glucocorticoids and nonsteroidal anti-inflammatory drugs, including Ind, are ulcerogenic whereas EGF has historically been used in the treatment of gastric ulcers in Zollinger-Ellison syndrome (26). Effects of Ind are mediated through prostaglandin down-regulation and disturbed vascular circulation.…”

Section: Discussionmentioning

confidence: 99%

Hydrocortisone and Indomethacin Negatively Modulate EGF-R Signaling in Human Fetal Intestine

et al. 2007

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Concomitant use of hydrocortisone and the nonspecific cyclo-oxygenase (COX)-inhibitor indomethacin increases the risk for intestinal perforations in preterm infants. We determined whether this was associated with insufficient epidermal growth factor receptor (EGF-R) signaling. We tested the effect of EGF, hydrocortisone, and indomethacin on its activation, cell proliferation and migration, COX-2 expression, and prostaglandin E 2 (PGE 2 ) production. Human small intestine epithelial cell line FHsInt74 and EGF-Rdeficient mice [EGF-R (-/-)] were used as models. The data revealed that EGF-R signaling had a bimodal positive effect on fetal enterocyte: 1) it increased cell proliferation and migration synergistically with hydrocortisone and 2) up-regulated COX-2 mRNA expression and subsequent PGE 2 production. Correlating with this, COX-2 protein expression was down-regulated in EGF-R (-/-) intestine. Despite a positive effect on cell proliferation with EGF, hydrocortisone blunted the stimulatory effect of EGF on COX-2 expression and PGE 2 production. Addition of indomethacin even further inhibited the EGF-stimulated PGE 2 synthesis. The data suggest that concomitant use of indomethacin and hydrocortisone on preterm infants, who physiologically synthesize only low levels of EGF-R ligands, may lead to intestinal problems related to failure in cytoprotective and regenerative events.

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“…It is a potent inhibitor of gastric acid secretion (15) and promotes epithelial cell proliferation both in vitro and in vivo (16 (18). Synthetic oligodeoxynucleotides were prepared by a solid-phase method (19).…”

mentioning

confidence: 99%

Synthesis and secretion of human epidermal growth factor by Escherichia coli.

Oka¹,

Sakamoto²,

Miyoshi³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

145

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A synthetic gene for human epidermal growth factor (hEGF) was joined to a sequence encoding the signal peptide of Escherichia coli alkaline phosphatase. This hybrid gene was placed under the control of the alkaline phosphatase gene (phoA) promoter in a recombinant plasmid, which was used to transfect E. coli. The hybrid protein that was expressed in host cells under conditions of phosphate limitation was processed accurately during the secretion process, and mature hEGF was recovered in the periplasmic fraction. On the other hand, no EGF was detected in the periplasmic space when the synthetic hEGF gene was not accompanied by the phoA signal sequence.

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Effect of Urogastrone in the Zollinger-Ellison Syndrome

Cited by 36 publications

References 24 publications

Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

Hydrocortisone and Indomethacin Negatively Modulate EGF-R Signaling in Human Fetal Intestine

Synthesis and secretion of human epidermal growth factor by Escherichia coli.

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