Polyamines inhibit myosin phosphatase and increase LC20 phosphorylation and force in smooth muscle
Swärd, K.; Pato, M.D.; Nilsson, B.O.; Nordström, I.; Hellstrand, P.
American Journal of Physiology 269(3 Pt 1): C563-C571
1995
ISSN/ISBN: 0002-9513 PMID: 7573385 Document Number: 451863
The increase in Ca-2+-activated force caused by polyamines in beta-escin-permeabilized guinea pig ileum is shown to be associated with increased myosin 20-kDa light chain (LC-20) phosphorylation and shortening velocity. Myosin LC-20 dephosphorylation with arrested kinase activity was slower in the presence of 1 mM spermine. Smooth muscle phosphatases (SMP-I, -II, -III, and -IV) isolated from turkey gizzard are all active against phosphorylated LC-20, but only SMP-III and -IV dephosphorylate heavy meromyosin (HMM). Spermine inhibited SMP-III activity toward LC-20 but stimulated HMM dephosphorylation, whereas SMP-IV was inhibited with both substrates. In contrast, SMP-I and -II were stimulated by spermine. The relative effects of different polyamines correlated with an increasing number of positive charges. Spermine did not affect binding of SMP-IV to myosin and did not dissociate any of the subunits of the enzyme. Incubation of permeabilized strips with SMP-IV resulted in attenuated responses to Ca-2+, an effect that was opposed by spermine and abolished by microcystin-LR. We conclude that spermine selectively inhibits myosin phosphatase activity and suggest that polyamines function as endogenous myosin phosphatase inhibitors.