Distinct receptors for epidermal growth factor-urogastrone in cultured gastric smooth muscle cells

1991 ◽  
Vol 260 (6) ◽  
pp. G827-G834
Author(s):  
S. G. Yang ◽  
M. D. Hollenberg
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Guinea Pig ◽  
Thymidine Incorporation ◽  
Circular Muscle ◽  
Relative Order ◽  
Binding Affinities ◽  
High Affinity ◽  
Epidermal Growth

We describe a propagable cell strain from guinea pig gastric circular muscle (GCM), which we have characterized in terms of its smooth muscle phenotype and its binding and biological response (thymidine incorporation) to epidermal growth factor-urogastrone (EGF-URO) and transforming growth factor-alpha (TGF-alpha). The binding of 125I-labeled EGF-URO to the GCM cells exhibited high affinity and an appropriate peptide specificity. A curvilinear Scatchard plot of the binding data indicated two classes of high-affinity binding sites (dissociation constants of 0.69 and 4.3 nM) and a maximal binding capacity of 24,000 sites/cell. Binding competition data demonstrated that the binding affinity of TGF-alpha was greater than that of EGF-URO by a factor of 2. These relative binding affinities agreed with the two- to threefold greater potency of TGF-alpha, compared with EGF-URO, for the stimulation of GCM thymidine incorporation. The relative order of binding affinity and biological potency (TGF-alpha greater than EGF-URO) was distinct from the relative order of binding affinities (EGF-URO greater than TGF-alpha) observed using guinea pig liver and human placental membrane preparations. We conclude that the cultured smooth muscle-derived GCM cells possess a receptor subtype that is in accord with contractile bioassay data obtained previously with intact gastric circular muscle strips. This receptor (TGF-alpha greater than EGF-URO) appears distinct from the one previously characterized in nonmuscle tissues.

Contraction of guinea pig trachea by epidermal growth factor – urogastrone

1988 ◽  
Vol 66 (10) ◽  
pp. 1308-1312 ◽  
Author(s):  
P. Patel ◽  
H. Itoh ◽  
K. Lederis ◽  
M. D. Hollenberg
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Guinea Pig ◽  
Muscle Tone ◽  
Induced Response ◽  
Organ Bath ◽  
Smooth Muscle Contractility ◽  
Significant Difference ◽  
Epidermal Growth

To evaluate further the action of epidermal growth factor – urogastrone (EGF–URO) in smooth muscle systems, we examined the effect of the peptide on guinea pig tracheal strips. The cumulative addition of EGF–URO to the organ bath resulted in a concentration-dependent tonic contraction without tachyphylaxis. The half-maximal contraction was obtained at 13 ± 3 ng/mL EGF–URO (2 nM). The maximum contraction at 100 ng/mL approached 60% of that induced by 1 μM histamine. No significant difference in the EGF–URO-induced contraction was observed in the presence or absence of a functional epithelium, Preincubation with 1 μM indomethacin for 20 min abolished the action of EGF–URO. The contractile effect of EGF–URO was not affected by yohimbine, propranolol, atropine, tetrodotoxin, and esculetin. However, mepacrine caused inhibition by 37 ± 7% (mean ± SEM for n = 3). Verapamil (10 μM) inhibited the EGF-induced response by 62 ± 5% (mean ± SEM for n = 4); the response was also absent in Ca-free (1 mM EGTA) buffer. However, the response was restored after the readdition of calcium. Our results suggest that EGF–URO can modulate tracheal smooth muscle contractility via a cyclooxygenase product and raise the possibility that EGF–URO might play a role in controlling pulmonary smooth muscle tone in vivo.

scholarly journals Transforming growth factor-beta modulates the high-affinity receptors for epidermal growth factor and transforming growth factor-alpha.

1985 ◽  
Vol 100 (5) ◽  
pp. 1508-1514 ◽  
Author(s):  
J Massagué
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Affinity Labeling ◽  
Tgf Beta ◽  
Semisolid Medium ◽  
High Affinity ◽  
Receptor Structure ◽  
Epidermal Growth

The epidermal growth factor (EGF) receptor mediates the induction of a transformed phenotype in normal rat kidney (NRK) cells by transforming growth factors (TGFs). The ability of EGF and its analogue TGF-alpha to induce the transformed phenotype in NRK cells is greatly potentiated by TGF-beta, a polypeptide that does not interact directly with binding sites for EGF or TGF-alpha. Our evidence indicates that TGF-beta purified from retrovirally transformed rat embryo cells and human platelets induces a rapid (t 1/2 = 0.3 h) decrease in the binding of EGF and TGF-alpha to high-affinity cell surface receptors in NRK cells. No change due to TGF-beta was observed in the binding of EGF or TGF-alpha to lower affinity sites also present in NRK cells. The effect of TGF-beta on EGF/TGF-alpha receptors was observed at concentrations (0.5-20 pM) similar to those at which TGF-beta is active in promoting proliferation of NRK cells in monolayer culture and semisolid medium. Affinity labeling of NRK cells and membranes by cross-linking with receptor-bound 125I-TGF-alpha and 125I-EGF indicated that both factors interact with a common 170-kD receptor structure. Treatment of cells with TGF-beta decreased the intensity of affinity-labeling of this receptor structure. These data suggest that the 170 kD high-affinity receptors for EGF and TGF-alpha in NRK cells are a target for rapid modulation by TGF-beta.

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