Kallikrein stimulates arachidonic acid release and production of prostaglandins from TEA3A1 endocrine thymic epithelial cells.
Using TEA3A1 rat endocrine thymic epithelial cells, we demonstrated that kallikrein (EC 3.4.21.35) not only stimulated the release of arachidonic acid (AA) and its metabolites from TEA3A1 cells but also enhanced the intracellular synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) by approx. 2-fold. The stimulatory effect of kallikrein was dose- and time-dependent and could be blocked by aprotinin, a kallikrein inhibitor. It was found that the phospholipase A inhibitors ONO RS082 [2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid], and mepacrine (6-chloro-9-[(4-dimethylamino)-1-methyl)]amino-2-methoxyacridine; quinacrine) also inhibited the kallikrein-stimulated release of AA and its metabolites. It is suggested that the kallikrein-induced stimulatory effect might be mediated through a phospholipase A2 pathway. The effect of bradykinin was studied and no significant stimulation was observed, even at a high dose (10 micrograms/ml). This suggested that the formation of kinin does not have a role in the kallikrein-induced stimulation of AA release from TEA3A1 cells. Furthermore, the effect of kallikrein was also totally abolished by adding pepstatin A, a known inhibitor of renin, pepsin and cathepsin D which does not inhibit kallikrein itself. This indicates that kallikrein did not act on the phospholipase-like enzyme directly. There is at least one more enzyme, a pepstatin A-inhibitable proteinase, that acts as a mediator for kallikrein-induced regulation of AA release.
Sun
L
L
W. Alton Jones Cell Science Center, Inc., Lake Placid, NY 12946.
Piltch
A
A
Hayashi
J
J
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis*; D004848:Epithelium; D007610:Kallikreins / Q000494:pharmacology*; D010436:Pepstatins / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D051381:Rats; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013950:Thymus Gland / Q000378:metabolism*
D001095:Arachidonic Acids; D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D016718:Arachidonic Acid; D013929:Thromboxane B2; D010741:Phospholipases A; D054467:Phospholipases A2; D007610:Kallikreins; D015232:Dinoprostone; D001920:Bradykinin; C031375:pepstatin