Mechanism of the stimulatory effect of 6-aminohexanoic acid on plasminogen activation by streptokinase or tissue plasminogen activator: the role of chloride.
Studies were conducted on the mechanism of the stimulatory effect of 6-aminohexanoic acid (6-AH) during the in vitro activation of human glutamic plasminogen (Glu-Plg) by streptokinase or by tissue plasminogen activator (t-PA) and the possible role of the addition of physiological concentrations of NaCl to the buffer solution. Enhancement by 6-AH was investigated by measuring the rate of plasmin generation using chromogenic substrate H-D-glu-phe-lys-pNA (S-2403). Control studies using plasmin showed that the addition of 6-AH at concentrations below 20 mM did not significantly affect the initial rate of the amidolytic activity of plasmin with or without the addition of NaCl to 0.05 M Tris buffer (pH 7.4). On the other hand, addition of NaCl to the buffer slowed down the initial rate of activation of Glu-Plg by streptokinase or by t-PA while increasing the percent enhancement by 6-AH when compared with the controls. The ratios of the initial rates of plasmin generation in the presence or in the absence of 6-AH were plotted against the inverse of the volume fraction of Glu-Plg, streptokinase or t-PA after serial dilutions. The results showed that when the activation reactions were performed in 50 mM of Tris buffer (pH 7.4), the enhancements by 6-AH were related to its interaction with streptokinase or t-PA, while using the same Tris buffer containing 0.6 % NaCl, the enhancements by 6-AH were related to its interaction with both Glu-Plg and streptokinase or t-PA. However, upon increasing the NaCl to 0.9%, the results showed that the enhancements by 6-AH of the activation of Glu-Plg by streptokinase or t-PA were related to its interaction with Glu-Plg. The results suggested that changes in the concentrations of NaCl play a regulatory role during the activation process.
Guinn
L
L
Department of Chemistry, Prairie View A&M University, Prairie View, Texas 77446, USA.
Doctor
V M
VM
D015119:Aminocaproic Acid / Q000494:pharmacology*; D002021:Buffers; D002712:Chlorides / Q000502:physiology*; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D013268:Stimulation, Chemical; D013300:Streptokinase / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D002021:Buffers; D002712:Chlorides; D012965:Sodium Chloride; D010958:Plasminogen; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D015119:Aminocaproic Acid