Abstract
ABSTRACT: To determine the pathophysiologic significance of pertussis toxin (PT) on the human β -adrenergic system, β -adrenoceptor (β -R)-density and cyclic AMP response of peripheral mononuclear blood cells (MN leukocytes) were studied in children during the paroxysmal stage of natural pertussis infection, after vaccination with pertussis monovaccine, and in controls. Isoprenaline-induced cAMP accumulation, measured in a protein-binding assay, was significantly reduced to about 25-50% in children during the first week of paroxysmal pertussis, compared with controls. In contrast, cAMP accumulation after stimulation of the adenylyl cyclase by forskolin was unaffected. The density and affinity of β -R, estimated by 125I-cyanopindolol- binding studies, were not significantly altered. The suggestion that PT might impair the coupling of the β -R signals to the adenylyl cyclase was confirmed by parallel in vitro studies on MN leukocytes from adults. These cells, when incubated with purified PT, showed a significantly diminished cAMP response to isoprenaline, whereas that to forskolin remained unaffected. As cAMP accumulation in response to prostaglandin E1 and hydrocortisone was also reduced, it appears that PT may directly affect Gproteins serving as signal transducers for several stimulatory receptors. In contrast to the actual disease, in children treated with pertussis monovaccine, cAMP accumulation as well as the β -R were unaffected. It is concluded that in MN leukocytes obtained from children during the natural course of pertussis, as well as after incubation of normal MN leukocytes with PT, the stimulatory signal-transducing system for cAMP generation is inhibited.
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Griese, M., Sideropoulou, O. & Reinhardt, D. Impaired Formation of the Second Messenger cAMP in Mononuclear Blood Cells of Children with Pertussis. Pediatr Res 25, 209–213 (1989). https://doi.org/10.1203/00006450-198902000-00026
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DOI: https://doi.org/10.1203/00006450-198902000-00026
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