Haemophilus influenzae-induced decreases in lung beta-adrenoceptor function and number coincide with decreases in spleen noradrenaline.
In the guinea-pig intraperitoneal administration of the Gram-negative bacterium Haemophilus influenzae induces a decrease of beta-adrenoceptor number and results in impairment of beta-adrenoceptor function in the peripheral and central airways, respectively. In the present study, the time-course of these events was studied and compared with changes in catecholamines in plasma, in organs involved in immunoregulation (spleen, thymus), and in the heart and the lung. The number of beta-adrenoceptor binding sites in peripheral lung tissue and beta-adrenoceptor function in isolated tracheal spirals were significantly decreased 3 and 4 days after administration of H. influenzae (24-33%). No significant changes were observed at day 1 and day 8. The effects on tracheal beta-adrenergic receptor function were characterized by a decrease of maximal relaxation only, whereas EC50-values were not affected. These data are indicative of an effect on the functional coupling of the receptors to the biochemical events leading to smooth muscle relaxation. No changes were observed in catecholamine concentrations in the lung, heart, and the thymus after H. influenzae-treatment. Plasma noradrenaline, though, was significantly increased at day 1 after H. influenzae. At day 8 plasma noradrenaline had returned to control levels. Interestingly, the effect on spleen noradrenaline was opposite to the effect seen in plasma. A significant decrease in spleen noradrenaline was observed after H. influenzae at days 1, 3, and 8, with a maximum of 42% at day 1. It is suggested that the decrease in spleen noradrenaline may have a causal relationship with the changes in lung beta-adrenoceptors.
Engels
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F
Institute for Veterinary Pharmacology, Pharmacy, and Toxicology, Department of Pharmacology, Faculty of Veterinary Sciences, Utrecht, The Netherlands.
Folkerts
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G
van Heuven-Nolsen
D
D
Nijkamp
F P
FP
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D006168:Guinea Pigs; D006193:Haemophilus influenzae / Q000276:immunology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000378:metabolism* / Q000503:physiopathology; D013154:Spleen / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D002217:Carbachol; D007545:Isoproterenol; D009638:Norepinephrine