Catecholamines released from the adrenal medulla exert a compensatory, protective effect at beta 2-adrenoceptors against Paf-induced death in mice.
1. The effects of a number of drugs and experimental conditions, which inhibit or stimulate adrenergic function, were evaluated on platelet-activating factor (Paf)-induced death in conscious mice. 2. Adrenalectomy markedly potentiated Paf toxicity, while guanethidine and reserpine did not. However, reserpine, which produced a virtually complete depletion of catecholamines (CA) in cardiac tissue, was not able to reduce adrenal CA by more than 58%. Drugs which release noradrenaline from the adrenergic nerve terminals, such as tyramine and amphetamine, did not protect mice from Paf toxicity, while drugs or conditions which favour the release of CA from the adrenal medulla, such as urethane and cold-induced stress, did. 3. beta 2- and beta 1 + beta 2-adrenoceptor antagonists (ICI 118551, propranolol and nadolol), but not beta 1-antagonists (atenolol, practolol, metoprolol and CGP 20712 A), potentiated Paf toxicity at low doses; beta 2- and beta 1 + beta 2-agonists (salbutamol, fenoterol and isoprenaline), but not beta 1-agonists (prenalterol and tazolol) were potent inhibitors of Paf toxicity. alpha 1- and alpha 2-adrenoceptor agonists and antagonists did not exert significant effects. Propranolol did not appear to enhance the hypotensive action of Paf in pentobarbitone-anaesthetized mice. 4. It is concluded that manipulation of the release of CA from the adrenal medulla, but not from adrenergic nerves, has profound effects on Paf toxicity in mice. A number of considerations support the hypothesis that bronchoconstriction is a major determinant of Paf-induced death in mice.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000315:Adrenalectomy; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D003080:Cold Temperature; D004347:Drug Interactions; D008297:Male; D051379:Mice; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology; D014520:Urethane / Q000633:toxicity
D000305:Adrenal Cortex Hormones; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D010972:Platelet Activating Factor; D011943:Receptors, Adrenergic, beta; D014520:Urethane; D012110:Reserpine