Inhibition of Carrageenin‐Induced Rat Paw Oedema by Catecholamines and Amine‐Depleting Drugs

Abstract

The anti‐inflammatory effects of adrenaline, isoprenaline, noradrenaline, tyramine, reserpine, guanethidine and fibrinolysin® were tested against carrageenin‐induced rat paw oedema. All the substances significantly inhibited the oedema. The inhibition by tyramine enhanced the effect of reserpine. The MAO‐inhibitor iproniazid potentiated the effect of noradrenaline and reduced the effect of reserpine. The in vivo effects of adrenaline, noradrenaline, reserpine and fibrinolysin on parameters of the plasma kinin system were investigated. Neither kininogen nor prekallikrein was influenced by any of the substances tested. The effect of noradrenaline, reserpine and guanethidine on the blood serotonin level was also investigated. Noradrenaline and guanethidine did not influence the serotonin level under experimental conditions which cause a significant reduction in the carrageenin‐induced rat paw oedema. The depletion by reserpine of the serotonin stores did not correlate with the rat paw oedema inhibition values. Nevertheless, a slight reduction in the blood concentration of serotonin after pedal injection of carrageenin might indicate a local release of the amine. Finally, plasminogen was estimated by a caseinolytic procedure in the plasma of rats injected with noradrenaline. Noradrenaline inhibited the rat paw oedema, but no reduction of the plasminogen level was observed. It was concluded that normal catecholamine stores rather than normal serotonin stores, and the application to the blood platelet serotonin, seemed essential for the development of carrageenin‐induced rat paw oedema. The fact that pretreatment with catecholamines inhibited the development of oedema might suggest that the same pathway of biochemical events is involved in the inflammatory process and in the preventive mechanism, the inhibition then reflecting an acute activation and depletion of a factor later in the sequence.

Dextran‐induced Lowering of Parameters of the Kallikrein‐kinin System in Rat Plasma: Significance of Monoamine‐depleting Agents

“…It is generally accepted that serotonin is the most important mediator in the fully developed anaphylactoid reaction induced by dextran in the rat, and it is also well established that reserpine in the doses used in the present work will deplete endogenous stores both of catecholamines and of serotonin in the rat. Under the chosen experimental conditions guanethidine, on the other hand, will mainly deplete catecholamines (Cass & Spriggs 1961;Arntzen & Briseid 1973). Taking these facts into consideration, the extents of the anaphylactoid reaction observed in the present work in rats pretreated with one or another of the two monoamine depletors provide strong evidence that catecholamines are not essential for the reaction, but indicate the significance of serotonin.…”

Prekallikrein Activator and Kallikrein in Acetone‐ and Kaolin‐activated Rat Plasma

“…Plasminogen-jiree rat ciirated plasma (RCPL-P). Freshly prepared RCPL was passed through a lysine-Sepharose 4 B column (Deutsch & Mertz 1970;March et al 1974) as described by Briseid et al (1978a).…”

“…Acetone-and kaolin-activated rat plasma (RP-Kall) was prepared from RCPL or RCPL-P as described by Briseid et al (1978a), with the modification that the preparation was incubated at 37O for 1 hour after evaporation in vacuo and before kaolin was added.…”

“…Determinations of prekallikrein activator (PKA) and kallikrein (K) were carried out as described by Briseid et al (1978a). The activities refer to ml RCPL or RCPL-Pin RP-Kall.…”

“…Determinaiion of PKA at 00 in kaolin-activated plasma was carried out according to Laake & Vennered( 1973a & b). Determination of caseinolytic activity was carried out by the methodofJacobsen(l964),asdescribed by Arntzen & Briseid (1973).…”