beta-escin and tautomycin

Phosphatase inhibitors microcystin-LR, tautomycin, and okadaic acid caused contraction and increased 20-kDa myosin light chain (MLC20) phosphorylation in Ca(2+)-free solutions in both phasic and tonic smooth muscle permeabilized with beta-escin, and inhibited the heavy meromyosin (HMM) phosphatase activity of smooth muscle homogenates with the same potency sequence: microcystin-LR greater than tautomycin greater than okadaic acid. The sensitivity to all three inhibitors was significantly higher, the half-times of relaxation and dephosphorylation were 4-6 times longer, and the HMM phosphatase and MLC20 kinase activity/smooth muscle cell wet weight was 2.0- and 1.9-fold lower in the tonic, femoral artery, than in the phasic, ileum or portal vein, smooth muscle. Preincubation with 0.2 microM inhibitor-2 decreased the HMM phosphatase activity by 35% in the ileum and by 60% in the femoral artery. The results suggest that the HMM phosphatases of smooth muscle have properties common to type 1 protein phosphatases, but are inhibited only partially by high concentrations of inhibitor-2, and that the lower HMM phosphatase activity of tonic smooth muscle may contribute to its greater sensitivity to phosphatase inhibitors and its slower rate of relaxation.

Topics: Animals; Antifungal Agents; Calcium; Cations, Divalent; Escin; Ethers, Cyclic; Guinea Pigs; In Vitro Techniques; Marine Toxins; Microcystins; Microscopy, Electron; Muscle Contraction; Muscle, Smooth; Muscle, Smooth, Vascular; Myosin-Light-Chain Phosphatase; Okadaic Acid; Peptides, Cyclic; Phosphoprotein Phosphatases; Phosphorylation; Pyrans; Rabbits; Spiro Compounds