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Alpha-thrombin and Trypsin Use Different Receptors to Stimulate Arachidonic Acid Metabolism

Alpha-thrombin and Trypsin Use Different Receptors to Stimulate Arachidonic Acid Metabolism

L Levine

Prostaglandins. 1994 Jun;47(6):437-49.

PMID: 7938615

Abstract:

Rat liver cells (the C-9 cell line) are stimulated to metabolize arachidonic acid by alpha-thrombin, its receptor polypeptide, gamma-thrombin, and trypsin. Prostaglandin (PG) I2 synthesis stimulated by alpha-thrombin is inhibited by dansylarginine N-(3-ethyl-1,5-pentanediyl) amide (DAPA), by hirudin, by the synthetic tyrosine-sulfated dodecapeptide corresponding to residues 53-64 of hirudin (hirugen), by the Tyr(SO3H)63-hirudin fragment 54-65 and by rabbit lung thrombomodulin. Stimulation of arachidonic acid metabolism by the receptor octapeptide, SFLLRNPN, is not affected by DAPA or hirudin. gamma-Thrombin stimulates arachidonic acid metabolism but at 300 to 400-fold higher concentrations. Trypsin stimulates arachidonic acid metabolism. Trypsin's proteolytic activity is required--its ability to stimulate is abolished if it is incubated with Na-p-tosyl-L-lysine chloromethyl ketone (TLCK) or bovine pancreatic trypsin inhibitor. Prior treatment of the rat liver cells with alpha-thrombin blocks subsequent stimulation by alpha-thrombin, but not by trypsin, whereas prior treatment with trypsin blocks subsequent stimulation by trypsin, but not the activity stimulated by alpha-thrombin. Prior treatment of the cells with the serine-proteases, chymotrypsin, pancreatic or neutrophil elastase and thrombocytin from Bothrups atrox venom, block alpha-thrombin's activation of PGI2 production, but not the activity stimulated by trypsin. These findings indicate that alpha-thrombin and trypsin stimulate PGI2 production via different receptors.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP109528496	[Tyr(SO3H)63]-Hirudin Fragment 54-65		109528-49-6	Price

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