In this grant, we propose an in vitro multidisciplinary study if the relationship between mast cells and neurons in autonomic ganglia. It has long been known that mast cells reside in autonomic ganglia, but there is virtually no information available on the function of these cells. We have found that mast cells in superior cervical ganglia isolated from actively sensitized guinea pigs degranulate and release inflammatory mediators (histamine, prostaglandin D2, and sulfidopeptide leukotrienes) upon enduring with specific antigen. Concomitantly, there is a robust and enduring (>3 hours) potentiation of synaptic transmission in these ganglia. To our knowledge, this represents the first demonstration of a direct communication between immunocompetent cells (presumably mast cells) and neurons in peripheral ganglia. This proposal is part of our long-range goal of understanding the role of nerve-associated mast cells in health and disease. To this end, we will combine neurophysiological, immunological and morphological methodologies to increase our understanding if the communication that exists between mast cells and nerves in sympathetic and airway parasympathetic ganglia of the guinea pig. Specifically, studies will be carried out: (1) to define the cellular locus (pre-v.s.postsynaptic) mechanisms underlying antigen induced long-term potentiation of synaptic transmission in the superior cervical ganglion; (2) to characterize the nature of the mediator(s) responsible for these physiological changes; (3) to delineate morphologic, biochemical, and pharmacological features if mast cells within the superior cervical ganglia; and (4) to investigate the influence of mast cell activation and inflammatory mediators on synaptic transmission through airway parasympathetic ganglia. These studies will add to our understanding if the physiology of sympathetic and parasympathetic ganglia. Apart from this intrinsic value, the will also provide insights into the pathophysiology of diseases such as bronchial asthma, where both allergic and neuronal components are thought to be involved.
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