Fig. 5. Model of the protein tyrosine kinase (PTK)–catalyzed, protein tyrosine phosphorylation–modulated signaling pathways for mediating vascular smooth muscle contraction. Tyrosine phosphorylation of a cascade of enzymes by PTKs causes multiple cell events, including cell growth, division, proliferation, and smooth muscle contraction. Tyrosine-phosphorylated phospholipase Cγ-1 (PLCγ-1) catalyzes phosphatidyl inositol bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG), which is involved in the release of Ca2+from the sarcoplasmic reticulum and activates protein kinase C (PKC), respectively. Tyrosine-phosphorylated p44/p42 mitogen-activated protein kinase (MAPK) by MAPK kinase (MEK) and PTKs catalyzes caldesmon to be phosphorylated and separated from actin, enhancing Ca2+sensitivity. Tyrosine phosphorylation of proteins is dephosphorylated by protein tyrosine phosphatase (PTPh), and the rate of dephosphorylation is decreased by PTPh inhibitors, such as sodium orthovanadate (Na3VO4). The current study demonstrates that isoflurane inhibits protein tyrosine–phosphorylated PLCγ-1–mediated and p42MAPK-mediated smooth muscle contraction. A II = angiotensin II; [Ca2+]i= intracellular calcium concentration; EGF = epidermal growth factor; NE = norepinephrine; PDGF = platelet-derived growth factor.