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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS025598-01
Application #
3410874
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Cavalcante de Albuquerque, A A; Leal-Cardoso, J H; Weinreich, D (1996) Antigen-induced synaptic plasticity in sympathetic ganglia from actively and passively sensitized guinea-pigs. J Auton Nerv Syst 61:139-44
Weinreich, D; Undem, B J; Taylor, G et al. (1995) Antigen-induced long-term potentiation of nicotinic synaptic transmission in the superior cervical ganglion of the guinea pig. J Neurophysiol 73:2004-16
Christian, E P; Weinreich, D (1992) Presynaptic histamine H1 and H3 receptors modulate sympathetic ganglionic synaptic transmission in the guinea-pig. J Physiol 457:407-30
Weinreich, D; Undem, B J; Leal-Cardoso, J H (1992) Functional effects of mast cell activation in sympathetic ganglia. Ann N Y Acad Sci 664:293-308
Undem, B J; Myers, A C; Weinreich, D (1991) Antigen-induced modulation of autonomic and sensory neurons in vitro. Int Arch Allergy Appl Immunol 94:319-24
Myers, A C; Undem, B J; Weinreich, D (1991) Influence of antigen on membrane properties of guinea pig bronchial ganglion neurons. J Appl Physiol 71:970-6
Undem, B J; Hubbard, W C; Christian, E P et al. (1990) Mast cells in the guinea pig superior cervical ganglion: a functional and histological assessment. J Auton Nerv Syst 30:75-87
Myers, A C; Undem, B J; Weinreich, D (1990) Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia. Am J Physiol 259:L403-9
Undem, B J; Myers, A C; Barthlow, H et al. (1990) Vagal innervation of guinea pig bronchial smooth muscle. J Appl Physiol 69:1336-46
Christian, E P; Undem, B J; Weinreich, D (1989) Endogenous histamine excites neurones in the guinea-pig superior cervical ganglion in vitro. J Physiol 409:297-312

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