Molecular responses of endothelial tissue to kinins.
The endothelial response to kinin stimulation is the result of a series of complex intracellular reactions involving changes in the intracellular concentration of free calcium ([Ca2+]i) and intracellular pH, enhanced phosphorylation of several proteins via the activation of at least four distinct families of protein kinases, and activation of membrane ion transport systems. Some of the more recent developments in this field suggest that endothelial tyrosine kinases and tyrosine phosphatases as well as serine/threonine phosphatases are also activated in response to bradykinin. In addition, the finding that the mitogen-activated protein kinase (MAP kinase) pathway was tyrosine phosphorylated, and presumably activated, in endothelial cells after an increase in [Ca2+]i has wideranging implications for these cells. Indeed, MAP kinase recognizes many different substrates in the cell, including growth factor receptors, microtubule-associated proteins, specific serine-threonine protein kinases, phospholipase A2, and transcription factors. Further recent studies of interest have underscored the role of endothelium-derived hyperpolarizing factor in addition to nitric oxide and prostacyclin in the coronary vasculature. Indeed, this mediator, which seems to be an endothelium-derived, cytochrome P450-derived metabolite of arachidonic acid, would now appear to represent a substantial constitutive component of the vasodilator response to bradykinin.
Busse
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Zentrum der Physiologie, Klinikum der JWG-Universität, Frankfurt/Main, Germany.
Fleming
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D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001920:Bradykinin / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D010738:Type C Phospholipases / Q000502:physiology
D001685:Biological Factors; D017923:Sodium-Hydrogen Exchangers; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017027:Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D001920:Bradykinin