Different modes of interaction of bradykinin with prostaglandins in pain and acute inflammation.
A mode of interaction of bradykinin with prostaglandins (PGs) in pain were compared with that in acute inflammation. When pain production was measured as an increase in reflex hypertensive response of the lightly anesthetized dogs after intrasplenic injection of bradykinin, the response was dependent to the doses (0.3-5 nmol) of bradykinin and that by the small doses (0.1-1 nmol) was blocked by intrasplenic infusion of indomethacin (0.54 mumol/min). The response to the threshold dose of bradykinin (0.3 nmol), which was suppressed during the indomethacin infusion, was potentiated by simultaneous injection of exogenous PGs. Order of the potency was PGI2 greater than PGH2 greater than PGE2 = TXA2 much greater than PGD2. Thus, it is clear that bradykinin induced pain through the generation of one of prostaglandins. On the other hand, the activity of bradykinin in plasma leakage was potentiated by simultaneous injection of PGE2, when tested in rabbit skin. In rat carrageenin-induced pleurisy, plasma prekallikrein was activated and high molecular weight (HMW) kininogen, not low molecular weight (LMW) kininogen, was consumed in the pleural cavity in the entire course of the pleurisy. Bradykinin played a role in plasma exudation in the pleurisy, because the plasma leakage was markedly inhibited in the rats, in which prekallikrein and HMW kininogen in plasma were depleted by intravenous bromelain. PGE2 was found in the pleural exudate, but the contribution of PGE2 itself to the plasma exudation seems to be only 10%. On the basis of the bradykinin release in the pleural cavity, once the PGE2 release was superimposed, the maximal plasma leakage was observed, indicating that PGE2 was released independently from bradykinin, and potentiated the plasma leakage by bradykinin.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D001963:Bromelains / Q000494:pharmacology; D004285:Dogs; D006973:Hypertension / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D010146:Pain / Q000503:physiopathology*; D011453:Prostaglandins / Q000494:pharmacology*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects; D012867:Skin / Q000187:drug effects
D011453:Prostaglandins; D001963:Bromelains; D001241:Aspirin; D001920:Bradykinin