Proteinase-activated receptor-2 activation induces uterine contractility in term pregnant rats that is not dependent on mast cell activation and cyclo-oxygenase products

Objectives: This study was undertaken to evaluate the effect of proteinase-activated receptor-2 (PAR-2) activation on the contractility of uterine tissues from term pregnant rats and the role of mast cells and prostaglandins in such an effect. Study Design: Uterine rings from pregnant (day 20-21) Sprague-Dawley rats were used for isometric tension recording in organ chamber experiments (Krebs solution, 5% carbon dioxide in air, 37°C, pH ˜7.4). Responses to the PAR-2 activating peptide SLIGRL (serine-leucine-isoleucine-glycine-arginine-leucine), and to the inactive reverse peptide LRGILS (leucine-arginine-glycine-isoleucine-leucine-serine) were determined after pretreatments with compound 48/80, cromolyn, S[+]-chlorpheniramine maleate, cimetidine, combinations of histamine (H) receptor antagonists with cromolyn or ibuprofen and compared with vehicle. Results SLIGRL significantly augmented contractility of uterine tissues, and this response was not inhibited by compound 48/80, cromolyn, and ibuprofen, as well as by H1- and H2-receptor antagonists, alone or in combination with cromolyn. Conclusion: PAR-2 activation augments uterine contractility in tissues obtained from term pregnant rats, and this effect is independent of mast cell activation or cyclo-oxygenase pathway products. (Am J Obstet Gynecol 2003;188:1498-1503.)