THROMBIN-MEDIATED EVENTS IMPLICATED IN MAST-CELL ACTIVATION

It has been suggested that mast cells contain receptors for thrombin b ecause binding of thrombin to peritoneal mast cells (PMCs) results in heparin release, Peritoneal mast cell responsiveness to different thro mbin forms was examined by measuring ion conductance, intracellular pH , the concentration of cyclic guanosine monophosphate (cGMP), and rele ase of histamine, Several types of receptors for thrombin are suggeste d by the results, which demonstrate that: (1) PMCs responded to alpha- thrombin and diisopryopyl-phosphoryl-alpha-thrombin (DIP-alpha-thrombi n), but not to gamma-thrombin, by activation of Na/H exchange in react ions involving protein kinase C and by a simultaneous elevation in cel l conductance and capacitance; (2) the initial 1-nmol/L alpha-thrombin -induced acidification of PMC cytoplasm was absent in Ca-free medium, and higher doses of alpha-thrombin induced a biphasic reaction (acidif ication preceeded alkalinization); and (3) PMC stimulation by alpha-th rombin at low concentrations (< 1 nmol/L) resulted in increase of cGMP and simultaneous decrease of histamine release, whereas thrombin conc entrations > 1 mu mol/L induced the acceleration of histamine release.