Epidermal growth factor-urogastrone causes vasodilatation in the anesthetized dog.

Abstract

Epidermal growth factor-urogastrone (EGF-URO) administered intraarterially was a potent dilator in dog femoral (FEM), superior (cephalic) mesenteric (SMA), celiac (CAC), coronary (COR), carotid (CAR), and renal (REN) vascular beds. The effects of EGF-URO, which exhibited tachyphylaxis, could not be attributed either to recirculating EGF-URO or to the secondary release ofother agonists or products ofthe cyclooxygenase pathway. Two vascular beds (FEM, SMA) showed a high maximum responsiveness to EGF-URO (maximum effect lEn,,,i 70% increase in flow) whereas another group (CAC, COR, CAR, and REN) exhibited lower responsiveness (E,, ,,-20%).The ED5o for this effect of EGF-URO was in the range of 0.4 Mpg (FEM, SMA, CAR, and COR) to 0.9 Mig (CAC and REN).In isolated dog COR helical strips, EGF-URO did not exhibit either a direct relaxing or a contractile effect. However, preincubation of strips with EGF-URO caused up to a 66% inhibition of contraction in response to norepinephrine (1 MM), with an EDso for EGF-URO of 1 nM. This action of EGF-URO also showed marked tachyphylaxis. Our data point to a potential role for EGF-URO (and possibly for the structurally related alphatransforming growth factor) in the regulation of blood flow in vivo.

Circulatory effects of a depilatory dose of mouse epidermal growth factor in sheep.

“…It is interesting to note that urogastrone (EGF-URO) was a potent dilator of the superior mesenteric and coeliac arterial beds when given intraarterially in anaesthetized dogs (Gan, MacCannell & Hollenberg, 1987).…”

Reduced ability of transforming growth factor-alpha to induce EGF receptor heterodimerization and downregulation suggests a mechanism of oncogenic synergy with ErbB2

“…TGFa is more widely expressed in normal adult tissues than is EGF, and the two ligands have comparable EGFR binding a nities (Lee et al, 1995). Despite this, TGFa may exert greater mitogenic potency than EGF in vitro (Gabelman and Emerman, 1992) and in vivo (Gan et al, 1987), suggesting that TGFa functions as an EGFR superagonist' in some cells and tissues. Moreover, unlike EGF, TGFa has been widely implicated in the pathogenesis of autocrine growth loops in cancer cells and tumours (Mellon et al, 1996;Muller et al, 1996;Stromberg et al, 1992).…”

Epidermal growth factor-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting tubule cells. Regulation by G protein, calcium, and protein kinase C.

“…In addition, it has been demonstrated to exert effects apparently unrelated to its mitogenicity such as inhibition of gastric acid secretion and vasodilatation (2,3). EGF has been demonstrated to stimulate phospholipase C (PLC) in several cell types, including a hepatocellular carcinoma line (4) and the A43 1 cell (5), a cell line that overexpresses the EGF receptor.…”