Summary
In the guinea-pig intraperitoneal administration of the Gram-negative bacterium Haemophilus infuenzae induces a decrease of β-adrenoceptor number and results in impairment of β-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 β-adrenoceptor binding sites in peripheral lung tissue and β-adrenoceptor function in isolated tracheal spirals were significantly decreased 3 and 4 days after administration of H. infuenzae (24–33%). No significant changes were observed at day 1 and day 8. The effects on tracheal β-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. infuenzae-treatment. Plasma noradrenaline, though, was significantly increased at day 1 after H. infuenzae. 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. infuenzae 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 β-adrenoceptors.
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References
Barnes PJ (1986) Neural control of human airways in health and disease. Am Rev Resp Dis 134:1289–1314
Bartell TE, Busse WW (1980) Effect of Bordetella pertussis vaccination in mice and the isolated tracheal response to isoprenaline. Allergy 35:291–296
Besedovsky H, del Rey A, Sorkin E, Da Prada M, Keller HH (1979) Immunoregulation mediated by the sympathetic nervous system. Cell Immunology 48:346–355
Boushey HA, Holtzman MJ, Sheller JR, Nadel JA (1980) Bronchial hyperreactivity. Am Rev Resp Dis 121:389–413
Buckner CK, Clayton DE, Ain-Shoka AA, Busse WW, Dick EC, Shult P (1981) Parainfluenza 3 infection blocks the ability of a β-adrenergic receptor agonist to inhibit antigen-induced contraction of guinea pig isolated airway smooth muscle. J Clin Invest 67:376–384
Carswell H, Nahorski SR (1983) β-Adrenoceptor heterogeneity in guinea-pig airways: comparison of functional and receptor labelling studies. Br J Pharmacol 79:965–971
Chuang D-M, Costa E (1979) Evidence for internalization of the recognition site of β-adrenergic receptors during receptor sub-sensitivity induced by (−)-isoproterenol. Proc Natl Acad Sci USA 76:3024–3028
Constatine JW (1965) The spirally cut tracheal strip preparation. J Pharm Pharmacol 17:384–385
De Lean A, Munson PJ, Rodbard R (1978) Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol 235:E97-E102
Del Rey A, Besedovsky HO, Sorkin E, Da Prada M, Bondiolotti GP (1982) Sympathetic immunoregulation: difference between high- and low-responder animals. Am J Physiol 242: R30-R33
Engels F, Oosting RS, Nijkamp FP (1987) Dual effects of Haemophilus influenzae on guinea pig tracheal β-adrenergic receptor function: involvement of oxygen-centered radicals from pulmonary macrophages. J Pharmacol Exp Ther 241:994–999
Felten DL, Felten SY, Carlson SL, Olschowka JA, Livnat S (1985) Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 135:755s-765s
Folkerts G, Nijkamp FP (1985) Haemophilus influenzae induces a potentiated increase in guinea-pig pulmonary resistance to histamine. Eur J Pharmacol 119:117–120
Haas H, Morris JF, Samson S, Kilbourn JP, Kim PJ (1977) Bacterial flora of the respiratory tract in chronic bronchitis: comparison of transtracheal, fiberbronchoscopic, and oropharyngeal sampling methods. Am Rev Resp Dis 116:41–47
Johansson L-H, Persson H, Rosengren E (1986) β2-Adrenoceptor selectivity in four series of β-adrenoceptor agonists. Eur J Pharmacol 130:97–103
Landy M, Sanderson RP, Jackson AL (1965) Humoral and cellular aspects of the immune response to the somatic antigen of Salmonella enteritidis. J Exp Med 122:483–504
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Lüderitz O, Galanos C, Rietschel ET (1982) Endotoxins of Gram-negative bacteria. Pharmacol Ther 15:383–402
May JM, Abel PW, Minneman KP (1985) Binding of agonists and antagonists to β-adrenoceptors in rat vas deferens: relationship to functional response. Naunyn-Schmiedeberg's Arch Pharmacol 331:324–333
Möller G (1965) 19S Antibody production against soluble lipopolysaccharide antigens by individual lymphoid cells in vitro. Nature 207:1166–1168
Morrison DC, Ryan JL (1979) Bacterial endotoxins and host immune responses. Adv Immunol 28:293–450
Moyle WR, Lee EY, Bahl OP, Garfink JE, Rodbard D (1977) New method for quantifying ligand binding based on measurement of an induced response. Am J Physiol 232: E274-E285
Norris AA, Eyre P (1981) Impairment of pharmacological modulation of airways smooth muscle by a respiratory pathogen. J Pharm Pharmacol 33:470–472
Norris AA, Eyre P (1982) Pharmacological abnormality in bronchial asthma and the role of respiratory pathogens. Medical Hypotheses 8:199–205
Nijkamp FP (1985) Hyperreactivity, inflammation and the β-adrenoceptor. In: Bonta IL, Bray MA, Parnham MJ (eds) Handbook of inflammation, vol 5, Elsevier Science Publishers, Amsterdam, pp 335–354
Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci USA 51:660–672
Schreiner A, Bjerkestrand G, Digranes A, Halvorsen FJ, Kommedal TM (1978) Bacteriological findings in the transtracheal aspirate from patients with acute exacerbations of chronic bronchitis. Infection 6:54–56
Schreurs AJM, Terpstra GK, Raaymakers JAM, Nijkamp FP (1980a) The effects of Haemophilus influenzae vaccination on anaphylactic mediator release and isoprenaline-induced inhibition of mediator release. Eur J Pharmacol 62:261–268
Schreurs AJM, Terpstra GK, Raaymakers JAM, Nijkamp FP (1980b) Effects of vaccination with Haemophilus influenzae on adrenoceptor function of tracheal and parenchymal strips. J Pharmacol Exp Ther 215:691–696
Schreurs AJM, Nijkamp FP (1982a) Haemophilus influenzae induced loss of lung β-adrenoceptor binding sites and modulation by changes in peripheral catecholaminergic input. Eur J Pharmacol 77: 95–102
Schreurs AJM, Versteeg DHG, Nijkamp FP (1982b) Involvement of catecholamines in Haemophilus influenzae induced decrease of β-adrenoceptor function. Naunyn-Schmiedeberg's Arch Pharmacol 320:235–239
Schreurs AJM, Verhoef J, Nijkamp FP (1983) Bacterial cell-wall components decrease the number of guinea pig lung β-adrenoceptors. Eur J Pharmacol 187:127–132
Schreurs AJM, Nijkamp FP (1984) Bronchial hyperreactivity to histamine induced by Haemophilus influenzae vaccination. Agents and Actions 15: 211–215
Snavely MD, Motulsky HJ, Moustafa E, Mahan LC, Insel PA (1982) β-Adrenergic receptor subtypes in the rat renal cortex. Selective regulation of β1-adrenergic receptors by pheochromocytoma. Circ Res 51:504–513
Szentivanyi A (1968) The beta adrenergic theory of the atopic abnormality in bronchial asthma. J Allergy 42:203–232
Tsujimoto G, Manger WM, Hoffman BB (1984) Desensitization of β-adrenergic receptors by pheochromocytoma. Endocrinology 114:1272–1278
Van der Gugten J, Palkovits M, Wijnen HJLM, Versteeg DHG (1976) Regional distribution of adrenaline in rat brain. Brain Res 107:171–175
Van Heuven-Nolsen D, De Wildt DJ, Nijkamp FP (1985) Disturbed adrenergic regulation of coronary flow in the guinea-pig heart after endotoxin. Eur J Pharmacol 118: 341–345
Van Heuven-Nolsen D, Folkerts G, De Wildt DJ, Nijkamp FP (1986) The influence of Bordetella pertussis and its constituents on the beta-adrenergic receptor in the guinea pig respiratory system. Life Sci 38:677–685
Vigholt Sorensen E, Nielsen-Kudsk F (1986) Single and combined myocardial pharmacodynamics of xamoterol, isoprenaline and g-strophanthin in the isolated rabbit heart. Eur J Pharmacol 125:363–371
Zaagsma J, Oudhof R, van der Heijden PJCM, Plantje JF (1979) Subheterogeneity of β-adrenoceptors in the pulmonary and the cardiac system of the guinea pig. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: Basic and clinical frontiers, Pergamon Press, New York, pp 435–437
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Engels, F., Folkerts, G., van Heuven-Nolsen, D. et al. Haemophilus influenzae-induced decreases in lung β-adrenoceptor function and number coincide with decreases in spleen noradrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 336, 274–279 (1987). https://doi.org/10.1007/BF00172678
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DOI: https://doi.org/10.1007/BF00172678