Pulmonary anti-anaphylactic activity of clenbuterol tested on actively and passively sensitized guinea-pigs.
Clenbuterol, an adrenergic beta-mimetic agent free of cardiostimulant effects, prevents the release of histamine from isolated rat mast cells. We studied its anti-anaphylactic activity in guinea-pigs and compared it with that of isoprenaline. At doses inactive against the bronchoconstriction caused by 5HT, clenbuterol (3 micrograms/kg) and isoprenaline (0.1-0.3 micrograms/kg) prevented the bronchoconstriction due to 1 mg/kg ovalbumin infused into passively sensitized animals. Clenbuterol and isoprenaline (0.5-1 microM) inhibited by 40% the contractions of superfused parenchyma lung strips from actively sensitized animals, stimulated with 0.3, 1 and 10 micrograms of ovalbumin. When strips from passively sensitized animals were challenged in the organ bath, clenbuterol and isoprenaline (0.01 microM) reduced by 50% the contraction triggered by 10 micrograms/ml of ovalbumin. These concentrations of clenbuterol were ineffective against contractions caused by acetylcholine. Clenbuterol and isoprenaline (0.001-0.01 microM) inhibited the release of histamine and of thromboxane A2 triggered by ovalbumin (0.1, 1 and 10 micrograms) injected into isolated lungs from actively sensitized guinea-pigs indicating that the anti-anaphylactic properties of clenbuterol are independent from its smooth muscle relaxing activity.
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Lagente
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Lefort
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Vargaftig
D000109:Acetylcholine / Q000494:pharmacology; D000707:Anaphylaxis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002976:Clenbuterol / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007114:Immunization; D007116:Immunization, Passive; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism
D004983:Ethanolamines; D012701:Serotonin; D013928:Thromboxane A2; D007545:Isoproterenol; D000109:Acetylcholine; D002976:Clenbuterol