Heparin-, dextran sulfate- and protamine-induced release of extracellular-superoxide dismutase to plasma in pigs.
Intravenous heparin has previously been shown to release the high-heparin-affinity fraction C of extracellular-superoxide dismutase (EC-SOD, EC 1.15.1.1) to plasma in man and other mammals. This paper reports on further studies of the phenomena in the pig. A dose-response curve of the effect of heparin revealed that 1000 IU/kg body weight is needed for maximal release of EC-SOD C. This dose is an order of magnitude larger than that needed for the maximal release to plasma of factors such as lipoprotein lipase, hepatic lipase, and diamine oxidase, which are distributed between plasma and endothelium similarly to EC-SOD C. Thus EC-SOD C appears to have an unusually high affinity for endothelial cell-surface sulfated glycosaminoglycans relative to the affinity for heparin. There was no significant difference in releasing potency between unfractionated heparin and heparin subfractions with high or low affinity for antithrombin III. The heparin structure conferring high-affinity binding to antithrombin III is thus not specifically involved in binding to EC-SOD C. The non-biosynthetic compound dextran sulfate 5000 was an order of magnitude more efficient than heparin. Protamine displayed dual effects. Given alone in high dose it released EC-SOD to plasma, probably due to binding to endothelial cell-surface sulfated glycosaminoglycans displacing fraction C of the enzyme. When given after heparin, in a dose just below that expected to neutralize the heparin, protamine reversed the heparin-induced EC-SOD release.
Karlsson
K
K
Department of Clinical Chemistry, Umeå University Hospital, Sweden.
Marklund
S L
SL
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D002850:Chromatography, Gel; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D011479:Protamines / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000097:blood*; D013552:Swine
D003911:Dextrans; D011479:Protamines; D000990:Antithrombin III; D006493:Heparin; D016264:Dextran Sulfate; D013482:Superoxide Dismutase