Thrombin-Mediated Events Implicated in Mast Cell Activation

Abstract

It has been suggested that mast cells contain receptors for thrombin because binding of thrombin to peritoneal mast cells (PMCs) results in heparin release. Peritoneal mast cell responsiveness to different thrombin forms was examined by measuring ion conductance, intracellular pH, the concentration of cyclic guanosine monophosphate (cGMP), and release of histamine. Several types of receptors for thrombin are suggested by the results, which demonstrate that: (1) PMCs responded to α-thrombin and diisopryopyl-phosphoryl-α-thrombin (DIP-a-thrombin), but not to γ-thrombin, by activation of Na/H exchange in reactions involving protein kinase C and by a simultaneous elevation in cell conductance and capacitance; (2) the initial 1-nmol/L α-thrombin-induced acidification of PMC cytoplasm was absent in Ca-free medium, and higher doses of α-thrombin induced a biphasic reaction (acidification preceeded alkalinization); and (3) PMC stimulation by α-thrombin at low concentrations (< 1 nmol/L) resulted in increase of cGMP and simultaneous decrease of histamine release, whereas thrombin concentrations > 1 μmol/L induced the acceleration of histamine release.

Keywords:

Peritoneal mast cells - histamine - cGMP - α-thrombin - protein kinase C