Duodenase Activates Rat Peritoneal Mast Cells Via Protease-Activated Receptors of Type 1
A. M. Makarova1 #, T. S. Zamolodchikova2, L. D. Rumsh2 and S. M. Strukova1
#Phone: (495) 939-14-16; fax: (495) 138-09-92; e-mail: Makarova_am@mail.ru
1 Faculty of Biology, Moscow State University, Vorob’evy gory, Moscow, 119899, Russia; 2 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia
Received: June 22, 2006; in final form: September 12, 2006
Abstract. It was found that duodenase, a serine protease from the bovine duodenum, activates rat peritoneal mast cells (PMC) in vitro presumably via protease-activated receptors (PARs). Like thrombin (a serine protease from the blood coagulation system) and the PAR1 agonist peptide (PAR1-AP), duodenase was shown to accelerate the secretion of β-hexosaminidase (a marker of cell degranulation) by PMC in a dose-dependent manner. The blockage of the proteolytic activity of duodenase toward the substrate Tos-Gly-Pro-Lys-pNA by the soybean Bauman-Birk protease inhibitor substantially reduced (by 40%) the ability of duodenase to stimulate the secretory activity of PMC. Pretreatment of PMC with duodenase decreased the β-hexosaminidase secretion induced by thrombin and PAR1-AP by 35 and 41.7 %, respectively, and abolished the antiinflammatory effect of activated protein C. At the same time, pretreatment of PMC with duodenase did not affect the secretion of β-hexosaminidase induced by compound 48/80, a nonspecific degranulator of mast cells. Duodenase, unlike PAR1-AP (30–100 μM), in a broad concentration range (10–100 nM) did not induce aggregation of human platelets, but suppressed the platelet aggregation elicited by PAR1-AP.
Key words: duodenase; inflammation; mast cells; PAR1 agonist peptide; protease-activated receptors; thrombin
Russian Journal of Bioorganic Chemistry 2007, 33(5): 482-487