Regulation of prostaglandin synthesis mediated by thrombin and b2 bradykinin receptors in a fibrosarcoma cell line

The murine fibrosarcoma cell line HSDM1C1 synthesizes prostaglandin E2 in response to thrombin and bradykinin, two products of the coagulation pathway. These physiologic effectors interact with two independent cell-surface receptor systems whose properties we have characterized. HSDM1 C1 cells possess a B2 bradykinin receptor, a type more sensitive to native bradykinin than to related peptides, including Met-Lys- and desArg 9-bradykinin. A period of bradykinin desensitization follows the initial response. Recovery occurs within 1 hr by a process independent of serum factors. The thrombin-mediated pathway differs in several respects. The maximum amount of prostaglandin E2 synthesized is 40% lower. Prolonged desensitization of the thrombin response occurs after an initial exposure; recovery requires at least 3 hr and depends strictly on the presence of serum. Antithrombin III and hirudin, two proteins that specifically inactivate thrombin, act in serum-free medium to relieve thrombin desensitization. Thrombin's prolonged desensitization thus suggests a persistent ligand-receptor association. The expression of receptor-mediated prostaglandin synthesis governed by multiple physiologic effectors in the same cell may reflect environmental conditions, such as the relative proportions of each effector and the presence of exogenous factors that modulate the ligand-receptor interaction.