[Alpha-thrombin stimulation of heparin secretion by the peritoneal mast cells in rats].
The interaction of alpha-thrombin with connective tissue-type mast cells (CTMC) purified by Ficoll density gradient centrifugation has been examined. It was demonstrated that exposure of CTMC to polymixin (widely used histamine liberator) (3 mg/ml) induced the release of heparin and histamine. Exposure of CTMC to 10(-11) M alpha-thrombin resulted in increase of heparin secretion by 75.5% in relation to basal level. CTMC which were stimulated by very low concentrations of alpha-thrombin (10(-11)-10(-8) M) can release high level of heparin, but not histamine. We have a suggestion that the thrombin specificity is connected with the additional recognition binding site for high molecular substrates (HMS) distinct from the active centre. Unlike alpha-thrombin which has both the active centre and the recognition site for HMS, beta/gamma-thrombin with catalytic activity but with disrupted recognition site induced the heparin release from mast cells only at higher concentrations than alpha-thrombin. It was revealed that DIP-alpha-thrombin without proteolytic activity was unable to activate mast cells in contrast to alpha-thrombin. We consider that alpha-thrombin induced release of heparin by CTMC account for proteolytic and hormone-like activity enzyme by means of both the active centre and the additional recognition site for HMS.
Umarova
B A
BA
Khlgatian
S V
SV
Strukova
S M
SM
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D010529:Peritoneal Cavity / Q000166:cytology*; D051381:Rats; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000031:analogs & derivatives / Q000494:pharmacology*
D006493:Heparin; D013917:Thrombin; C027962:diisopropylphosphoryl-thrombin
Stimuliatsiia al'fa-trombinom sekretsii geparina peritoneal'nymi tuchnymi kletkami krys.