ANTIGEN DEPOLARIZES GUINEA-PIG BRONCHIAL PARASYMPATHETIC GANGLION NEURONS BY ACTIVATION OF HISTAMINE H-1 RECEPTORS

Studies were carried out to evaluate the mechanism by which neurotrans mission through airway parasympathetic ganglia may be modulated during immediate hypersensitivity reactions. Guinea pigs were passively sens itized by injection of guinea pig serum containing high-titer anti-ova lbumin antibodies. Intracellular recordings were obtained from intrins ic parasympathetic ganglion neurons from the right mainstem bronchus i n vitro. Ovalbumin (10 mu g/ml) elicited a membrane potential depolari zation and changes in membrane resistance in bronchial ganglion neuron s from passively sensitized guinea pigs. Histamine mimicked the depola rizing effect of ovalbumin in a concentration-dependent manner (0.1-10 mu M) and caused a transient increase and decrease in membrane resist ance. Pyrilamine, a histamine H-1-receptor antagonist, inhibited the h istamine-induced membrane depolarization and decrease in resistance. B y contrast, blocking histamine H-2 and H-3 receptors did not inhibit h istamine-induced depolarization. Pyrilamine also reduced the antigen-i nduced depolarization of ganglion neurons, demonstrating a role for hi stamine H-1 receptors in this response. The data provide evidence that the antigen-induced depolarization of airway ganglion neurons is seco ndary to an antigen-antibody interaction on intrinsic mast cells and t he consequential effect of histamine on H-1 receptors. These studies d emonstrate that histamine released during an immediate hypersensitivit y reaction has direct effects on airway parasympathetic nerves.