EPIDERMAL GROWTH FACTOR STIMULATES CONTRACTION AND ATTENUATES COLD-INDUCED CONTRACTION IN NEWBORN LAMB MIDDLE CEREBRAL ARTERY (MCA): ROLE FOR PROTEIN TYROSINE KINASE. • 466

Previous studies suggest that protein tyrosine kinase (PTK)-dependent mechanisms modulate cold-induced contractile behavior of MCA. Epidermal growth factor (EGF) has been well known to initiate cellular responses via its ligand-induced activation of PTK activity intrinsic to the EGF receptor. Therefore, to further evaluate the role of PTK in the cold-induced contraction(CIC), we examined, using tissue bath technique, the effect of EGF on contractile properties of newborn lamb MCA. EGF (human recombinant) in concentrations of 1, 5, 10, and 90 nM caused a transient, dose-dependent increase in isometric force. The peak contraction amounted to 11±2, 21±2, 25±5%, and 19±1% of the maximal response to 120 mM KCl, respectively (p<0.05). This EGF-induced contraction was abolished following pretreatment with of genistein (20 μM), an inhibitor of PTK. Preliminary experiments further indicate that pretreatment with EGF (90 nM× 30′) caused a lack of responsiveness to subsequent EGF (10 nM) challenge and attenuated the contractile response to reduction of bath temperature (CIC[reduction of bath temperature from 37°C to 25°C and 17°C] = 68±12% and 95±6% KCl vs 30±7% and 76±9% KCl for control and EGF desensitized preparations, respectively). The data suggest that ligand activation of EGF receptor PTK activity stimulates MCA contraction. The finding that prolonged exposure to EGF results in loss of responsivness to EGF and attenuates CIC suggests common signaling mechanisms. These results support the notion that CIC involves PTK-dependent machinery which may form a basis for hypothermia-related cerebrovascular dysfunction. {Supported by American Heart Association national council,#95009270}

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Wagerle, L., Kim, S. & Russo, P. EPIDERMAL GROWTH FACTOR STIMULATES CONTRACTION AND ATTENUATES COLD-INDUCED CONTRACTION IN NEWBORN LAMB MIDDLE CEREBRAL ARTERY (MCA): ROLE FOR PROTEIN TYROSINE KINASE. • 466. Pediatr Res 39, 80 (1996). https://doi.org/10.1203/00006450-199604001-00486

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