Comparative effects of atrial polypeptide and neurohormone C on the interaction of factor Xa with antithrombin III.
The effects of atrial polypeptide and neurohormone C upon the interaction of human factor Xa (FXa) and human antithrombin III (ATIII) were followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. A pattern of bands consisting of a 1 degree duplex complex (FXaalpha-ATIII band of 109 kDa, FXabeta-ATIII band of 104 kDa), a 2 degree duplex complex (alpha band of 99 kDa, beta band of 95 kDa), a 3 degree duplex complex (alpha band of 66 kDa, beta band of 62 kDa), modified ATIII (ATIIIM, 58 kDa), native ATIII (55 kDa), FXaalpha (52 kDa), FXabeta (47 kDa), and a FXa degradation product (FXagamma, 35 kDa) was detected and quantitated. Preincubation of FXa, ATIII, or mixtures thereof with atrial polypeptide produced a shift from FXaalpha-ATIII to FXabeta-ATIII complexes and increases in both ATIIIM and FXagamma, reflecting degradation of the 1 degree and 2 degree complex to form the 3 degree complex. Atrial polypeptide appeared to promote FXa-ATIII complex formation when preincubated with ATIII, or when added within 1 min to FXa/ATIII mixtures. However, when atrial polypeptide was preincubated with FXa, inhibition of the 1 degree complex formation was suggested. Upon incubation of FXa, ATIII, or mixtures thereof with neurohormone C, there was an increase in total complex formation, a decrease in ATIIIM, a decrease in FXagamma, and little change in the ratio of free FXaalpha to FXabeta, or the ratio of FXaalpha-ATIII to FXabeta-ATIII complexes. Therefore, neurohormone C may act to suppress hydrolysis or proteolytic actions of excess FXa on FXa-ATIII complexes, or autolytic activity of FXa, to the level of FXagamma via an, as yet, unknown mechanism. Additionally, neurohormone C retards the hydrolysis of the FXa-ATIII complexes which form free FXa and ATIIIM. Hence, the role of atrial polypeptide in mixtures with ATIII and in mixtures with FXa is quite contrasting, and may reflect mechanistic effects of the atrial polypeptide molecule, as well as tissue-specific reactions.
Coggin
Martin H
MH
Department of Biological Sciences, Bowling Green State University, Bowling Green, OH 43403, USA.
Srapionian
Rima M
RM
Brecher
Arthur S
AS
Galoyan
Armen A
AA
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D015951:Factor Xa / Q000378:metabolism*; D006325:Heart Atria / Q000737:chemistry; D006801:Humans; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*
D007028:Hypothalamic Hormones; D010455:Peptides; C022043:neurohormone C; D000990:Antithrombin III; D015951:Factor Xa