Prostate specific antigen releases a kinin-like substance on proteolysis of seminal vesicle fluid that stimulates smooth muscle contraction

Purpose: We investigated whether purified prostate specific antigen (PSA), a seminal plasma serine protease of the kallikrein enzyme family, is capable of releasing kinin-like peptides from natural substrate glycoproteins in human seminal vesicle fluid. Materials and Methods: An in vivo rat bladder model was used to monitor for release of substances capable of inducing smooth muscle contractions. Purified PSA, seminal vesicle fluid (SVF) from radical prostatectomy specimens, bradykinin, saline and a bradykinin antagonist were injected intravesically into urethane-anesthetized rats, and the resulting bladder contractions were measured. Results: Injection of either PSA or SVF alone did not induce bladder contractions. Injection of a mixture of SVF and PSA preincubated 15 minutes, however, induced strong bladder contractions (23 +/- 7 cm. H2O) that decreased with time (4 +/- 2 cm. H2O, after 90 minutes). Similar contractions were observed after injection of bradykinin (10(-4) M. = 39 +/- 14, 10(-6) M. = 27 +/- 9, 10(-8) M. = 7 +/- 4 cm. H2O). Addition of a bradykinin antagonist to the PSA-SVF mixture prior to injection blocked the observed bladder contractions (23 +/- 7 cm. H2O before, versus 0.3 +/- 1.2 cm. H2O after adding antagonist). Conclusions: We conclude that PSA produces a kinin-like substance by enzymatic cleavage of glycoproteins in human seminal fluid. This substance induces smooth muscle contractions which can be specifically blocked by addition of a bradykinin antagonist.