Regulation of parasympathetic neurons by mast cells and histamine in the guinea pig heart

The potential interaction between the immune system and the autonomic nervo us system was examined in the cardiac ganglia of guinea pigs. Intracellular voltage recordings were used to determine the effects of mast cell degranu lation on the membrane properties of parasympathetic neurons in animals act ively sensitized to ovalbumin. Stimulation of mast cell degranulation by pe rfusion with ovalbumin (10 mug/ml) produced a depolarization and increase i n the excitability of intracardiac neurons. These effects could be mimicked by histamine application, either by perfusion (10 muM) or by local pressur e application (100 muM, 1-2 S application). In either case, histamine appli cation resulted in a similar membrane depolarization and increase in excita bility. Immunohistochemical experiments demonstrated that histamine-immunor eactive mast cells are located in close proximity to parasympathetic postga nglionic neurons. The histamine response was not due to release of other ne urotransmitters from adjacent nerve terminals and both the depolarization a nd increase in excitability were inhibited by the H-1 antagonist, pyrilamin e (300 nM), and were unaffected by the H-2 antagonist cimetidine (5 muM) in cubation of cardiac ganglion preparations from sensitized animals with pyri lamine prior to ovalbumin perfusion resulted in the inhibition of both the depolarization and increase in excitability. These results demonstrate that mast cell degranulation, and the subsequent release of histamine, results in the stimulation of intracardiac neurons via the activation of H-1 recept ors. Thus, local inflammatory reactions in the cardiac tissue can lead to t he rapid activation of parasympathetic neurons, thereby altering cardiac fu nction. (C) 2001 Elsevier Science B.V. All rights reserved.