Sensitization and Desensitization of Mice to Histamine and Serotonin by Neurohumors

Abstract

The urinary elimination pattern of normal mice following the injection of radioactive histamine and serotonin was compared with that of pertussis-treated animals. The absence of gross differences between these two groups suggested that the handling of histamine and serotonin by the body as a whole is not altered in the highly sensitive pertussis-vaccinated mouse. For this reason, it was concluded that the hypersensitivity is the result of a localized hyper-reactivity of the effector cells to normally nontoxic concentrations of histamine and serotonin. Attempts were therefore made to modify the sensitivity with a variety of neurohumoral agents known to react with the receptors of the neuroeffector cells. It was found that acute exposure to progressively increasing amounts of histamine and serotonin desensitized the pertussis-treated animals to these amines and the desensitization persisted for at least 24 hr. Cross-protection was also obtained; complete with histamine pretreatment against serotonin, incomplete with serotonin against histamine. However, desensitization attempts with another toxic amine (agmatine), not known to function as a neurohumor and whose toxicity for mice is not modified by pertussis-sensitization, demonstrated that the resistance of either normal or pertussis-treated mice to the same amine was not altered, nor was this procedure of any apparent value in protecting the latter animals against histamine. The agmatine disparity further emphasized the critical significance of neurohumors in the pertussis-induced sensitive state and led to the administration of various autonomic drugs which were shown to be protective in the pertussis-treated animals. Another such substance, dibenzyline (α-adrenergic blocking agent), was also protective in pertussis-sensitized animals, whereas a β-adrenergic blocking agent, dichloroisoproterenol, duplicated the histamine and serotonin hypersensitivity in normal animals. Based on these observations, the hypothesis is advanced that the pertussis-induced hypersensitivity is the result of a functional imbalance between two types of adrenergic effector systems, i.e., between two types of adrenergic receptors or in the neural pathways leading to them.