Abstract

Several lines of evidence support the concept that Bordetella pertussis-induced histamine hypersensitivity in mice represents a malfunction in beta-adrenergic receptors of the autonomic nervous system. In this study mouse platelets were used as an in vitro test for such receptor dysfunction. It was found, to our knowledge for the first time, that platelets of normal mice were subject to the aggregative action of adenosine diphosphate (ADP) with the response pattern resembling that reported for cells of certain other species. These "normal" platelets were not aggregated by epinephrine, norepinephrine, or isoproterenol (isuprel). However, pretreatment with these catecholamines potentiated the platelet response to ADP. Potentiation by norepinephrine was suppressed in the presence of dibenzyline (an alpha-receptor antagonist); blockade of beta-type receptors with propranolol reduced isuprel enhancement. An extract of B. pertussis influenced aggregation initiated by a combination of ADP and isuprel in a way quite similar to propranolol pretreatment. These observations suggested the possible role of adrenergic receptors in at least the enchancement phenomena and, moreover, pointed to those types of experiments which might distinguish a receptor disturbance. Platelets derived from pertussis-vaccinated mice were more responsive to ADP than were those from normal animals. This alteration appeared to be a property of the cells and not of the suspending medium. ADP-initiated aggregation was also enhanced in the presence of epinephrine and norepinephrine. However, pretreatment with isuprel did not have the same effect as noted for normal donor platelets. These results point to a disturbance at the beta-adrenergic receptor level and lend support to the concept of beta-blockade in pertussis-treated mice.

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