Interaction of heparin with myosin ATPase: possible involvement with the hemorrhagic activity and a correlation with antithrombin III high affinity-heparin molecules.
Up to 50% of [35S]-heparin molecules prepared from rat skin bind to rabbit muscle myosin ATPase, in a concentration dependent manner, producing a stable complex with a dissociation constant of 3 x 10(-7) M. The [35S]-heparin in the complex has a distinct electrophoretic behaviour and is precipitated by TCA together with myosin. Other [35S]-glycosaminoglycans, namely, heparan sulfate, dermatan sulfate and chondroitin sulfate also prepared from rat tissues are unable to form complexes with the enzyme. Among the sulfated glycosaminoglycans obtained from different sources only heparin is able to displace the bound [35S]-heparin from the ATPase. Heparin with high affinity for antithrombin III, prepared by antithrombin-affinity chromatography, dislodges up to 90% of the bound [35S]-heparin. Furthermore, antithrombin III-high affinity heparin shows a high affinity for myosin ATPase when compared to antithrombin III-low affinity heparin which shows a low affinity for the enzyme. It is also shown that myosin ATPase inhibits the "in vitro" plasma anticoagulant activity of heparin. These are suggestive that the special structure of the heparin molecules needed for the binding to antithrombin and myosin ATPase bears important similarities. The mechanism of the hemorrhagic effect of heparin is discussed in view of these interactions.
Tersariol
I L
IL
Departamento de Bioquímica, Escola Paulista de Medicina, São Paulo, Brazil.
Dietrich
C P
CP
Nader
H B
HB
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000990:Antithrombin III / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology*; D006494:Heparin Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009218:Myosins / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000494:pharmacology; D011485:Protein Binding; D013462:Sulfur Radioisotopes; D014661:Vasoconstriction / Q000187:drug effects*
D006025:Glycosaminoglycans; D006494:Heparin Antagonists; D013462:Sulfur Radioisotopes; D000255:Adenosine Triphosphate; D000990:Antithrombin III; D006493:Heparin; D009218:Myosins