PLASMA-CLEARANCE OF RAT BIKUNIN - EVIDENCE FOR RECEPTOR-MEDIATED UPTAKE

Bikunin is a chondroitin sulphate-containing protease inhibitor with a molecular mass of 25 kDa. It is secreted into the blood by hepatocyte s, and recent observations indicate that it may have an extravascular function. Here we have studied the plasma clearance of bikunin in rats and mice. On intravenous injection, radiolabelled bikunin was found t o have a half-life of 10 min; in rats with ligated renal arteries, the clearance time was twice as long, implying that the kidneys account f or half the uptake. As judged by gel filtration, the size of bikunin i s similar to that of albumin. Autoradiographic analysis of kidneys rem oved 2 min after the injection of radiolabelled bikunin indicated that , despite its size, bikunin is cleared by glomerular filtration. On li gation of the renal arteries, the plasma concentration of bikunin incr eased linearly to at least four times normal. This finding shows that the non-renal uptake system is saturated and therefore presumably rece ptor-mediated. Most of the non-renal uptake of injected bikunin was fo und to occur in non-visceral tissues such as the skin. Analysis of ski n samples by autoradiography after injection of radiolabelled bikunin suggested that bikunin had been transferred from the plasma to the int erstitial space.