TISSUE PROTHROMBIN - UNIVERSAL DISTRIBUTION IN SMOOTH-MUSCLE

Immunohistochemical analysis of surgically obtained porcine tissue sam ples reveals ubiquitous staining for prothrombin in organs rich in smo oth muscle content and universal staining of smooth muscle in tissue v asculature. The native character of tissue prothrombin is verified fir st by chromogenic substrate hydrolysis and hirudin inhibition after in cubation of tissue extracts with taipan snake venom and phospholipid. Western analysis of tissue extracts confirms the native zymogen molecu lar weight. In addition, prothrombin purified in good yield from porci ne uterus is activated by Echis carinatus venom which, like taipan ven om, is 4-carboxyglutamic acid-sensitive. After correction for blood (g ross heme) and interstitial fluid (albumin), excess functional prothro mbin is observed in extracts of tissues having abundant smooth muscle. In contrast with factor X, the yield of prothrombin purified from por cine uterus greatly exceeds that attributable to contamination by whol e blood. Northern blot analysis from selected bovine tissues extracted for polyadenylated messenger RNA is equivocal for prothrombin mRNA wi th the exception of liver, which is positive. It is concluded that fun ctionally intact prothrombin is widely distributed among tissues owing to smooth muscle content, although the mechanism of emplacement and p hysiologic significance of prothrombin in these tissues remains unclea r.