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Protective activity of ketoprofen lysine salt against the pulmonary effects induced by bradykinin in guinea-pigs
No full textWe investigated the capacity of ketoprofen lysine salt (KLS) to counteract the pulmonary effects of some mediators of airway inflammation. The protective effect of KLS and its R-isomer against bradykinin (BK) induced plasma extravasation in the airways and bronchoconstriction was evaluated in anaesthetized guinea-pigs, in parallel with the capacity of KLS to inhibit the production of thromboxane A2 (TXA2). Moreover, we studied the ability of KLS to modulate leukotriene C4 (LTC4) and acetylcholine (ACH) induced bronchoconstriction and the associated production of TXA2. Nimesulide (NIM) was used as the reference compound. KLS dose-dependently inhibited the bronchoconstriction and the associated production of TXA2 induced by BK, with closely related ID50 values of 31.2 and 34.0 micrograms/kg i.v., respectively. The protection was evident 10 min after KLS administration and, at 100 micrograms/kg i.v., lasted up to 2h, Moreover, KLS dose-dependently inhibited the increase in capillary permeability induced by BK, with a potency (ID50 23.4 micrograms/kg i.v.) slightly higher than that shown against the bronchoconstriction. KLS also prevented the bronchoconstriction and TXA2 production triggered by LTC4, but not ACH induced bronchoconstriction. In all the models studied, KLS was about 10 times more potent than NIM. These data demonstrate the capacity of KLS to counteract the bronchoconstriction induced by BK and LTC4 and to a large extent the airway inflammation induced by BK. Blockade of prostanoid production is likely to account for this protective effect, since the R-isomer of KLS was devoid of significant activity
Protection by two ginkgolides, BN-52020 and BN-52021, against guinea-pig lung anaphylaxis
No full textInterference between the ginkgolides BN-52020 and BN-52021 and the effects of PAF-acether on the cardiovascular and pulmonary functions of guinea-pigs has been studied. BN-52020 (ED50 = 1.1 mg/kg i.v.) and BN-52021 (ED50 = 0.78 mg/kg i.v.) inhibit bronchospasm, hypotension and concomitant generation of TXA2-like activity induced by PAF-acether in anaesthetized guinea-pigs. This protecting activity is specific against PAF-acether since the two ginkgolides do not affect bronchoconstriction, hypotension and TXA2-like activity in the circulating blood due to Histamine, Acetylcholine and LTC4. BN-52021 reduces in a concentration-dependent way the formation of TXB2 caused by PAF-acether in guinea-pig perfused lungs without interference with the effect of Histamine, LTC4 and Arachidonic acid on these tissues. Using actively sensitized (Ovalbumin) guinea-pigs BN-52020 (ED50 = 2.45 mg/kg i.v.) and BN-52021 (ED50 = 1.71 mg/kg i.v.) protect the animals from lethal immunological reaction suggesting that PAF-acether must play a role in the expression of anaphylactic bronchoconstriction and hypotension. The present results indicate that BN-52021 and in a lesser extent BN-52020, which are neither bronchodilators nor cyclooxygenase inhibitors, display a selective antagonistic activity against PAF-acether and may have potential therapeutical implication in asthma
Genotype dependent response of morphine and methionine-enkephalin on the electrically induced contractions of the mouse vas deferens
No full textAnalgesia and locomotor activity are genetically differentiated in C 57 and DBA mice. In fact, DBA strain, unlike C 57, is very sensitive to the analgesic effects of morphine. On the contrary, morphine elicits an increase of locomotor activity only in C 57 mice. We have used this genetic approach to study the in vitro response of vas dererens contractions to morphine and methionine-enkephalin. The results obtained are the following: 1. The percentage of morphine inhibition of the electrically evoked contractions of the longitudinal muscle of the vas deferens is greater in DBA strain, which is sensitive to the analgesic effects of morphine, than in C 57 mice in which morphine exerts a stimulating effect of the locomotor activity; 2. Met-enkephalin has been found to be more active than morphine on the same preparation; 3. The inhibitory effects of Metenkephalin appear to be greater in C 57 than in DBA mice; 4. Different doses of Naltrexone are required to reverse the effects of morphine and Met-enkephalin; 5. Cumulative doses of Met-enkephalin and morphine induce different responses in the vas deferens of C 57 and DBA mice. The results emphasize the usefulness to study analgesic activity in these strains of mice
Anticholinergic agents prevent guinea-pig airway constriction induced by histamine, bradykinin and leukotriene C4: Relationship to circulating TXA2
No full textVarious doses of histamine, bradykinin and leukotriene C4 caused bronchoconstriction in anaesthetized guinea-pigs which were breathing spontaneously or artificially ventilated; there was a simultaneous, dose-related increase in circulating TXA2. The animals were prepared for continuous recording of extracorporeal circulation in order to detect the appearance in the blood of bioassayable levels of TXA2 -like substance. Furthermore, a TXA2 derivative, the mono-O-Me-TXB2, was radioimmunoassayed. Atropine, oxytropium bromide and ipratropium bromide given in mumol doses prevented both the increased airway resistance and the release of TXA2-like substance in the blood Pirenzepine dihydrochloride was the least active of the drugs tested. The protecting activity of anticholinergics and the relationship with their ability to affect TXA2-like substance generation suggest a new site of action for these drugs besides the blockade of muscarinic receptors
Interaction between beta 1 and beta 2 adrenoceptors in the isolated guinea-pig trachea
No full textThe presence of β1 and β2 adrenoceptors is demonstrated in the guinea-pig tracheal smooth muscle and both receptors subserve the same function. The functional relationship between the two β-receptors in the quinea-pig trachea, which is difficult to explain, is discussed in relation to the capacity of β1 receptors to take over their function, if the β2 receptors are completely blocked
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