Studies utilizing a variety of experimental approaches have established the existence of an inhibitory nervous system in mammalian airways which is neither adrenergic nor cholinergic. As the neurotransmitter has not been identified, the system commonly is referred to as the nonadrenergic noncholinergic inhibitory system (NANCIS). The functional significance of this nervous system and its role in the pathophysiology of human airways disease are slowly being uncovered. A role for inflammation in the genesis of human airway hyperactivity also is emerging. However, the influence of the inflammatory process on the airway NANCIS is unknown. Also unknown is the identity of the chemical transmitter utilized by the system for postganglionic transmission. In addition, little is known about the system's basic pharmacological characteristics, save that it is insensitive to a variety of pharmacological antagonists enzymatic interventions. Previous studies in our laboratory have established the functional significance of the NANCIS in the intact cat. Experiments performed in vitro have since confined and extended these findings. The studies outlined in the current proposal will utilize in vivo, in situ, in vitro and analytical techniques to: (I) demonstrate release and determine the nature of the NANCIS chemical transmitter in airways; and (2) examine the role of the airway NANCIS in airway inflammatory disease by assessing whether inflammation per se influences NANCIS function and whether NANCIS activation plays a role in regulating the release of inflammatory mediators and the progression of airways inflammation. It is envisaged that elucidation of the interactions between the NANCIS and airway inflammation will provide new insights into the means by which inflammation is associated with airway hyperactivity. Further, identification of the NANCIS neurotransmitter will provide a foundation for the development of more effective therapeutic agents for the treatment of hyperactive airways disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL027025-10A2
Application #
3338880
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1987-01-01
Project End
1992-11-30
Budget Start
1992-01-22
Budget End
1992-11-30
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Type
Schools of Pharmacy
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Thompson, D C; Altiere, R J (1998) Differential susceptibility of tracheal contraction to nonadrenergic noncholinergic relaxation. J Pharmacol Exp Ther 284:19-24
Lindsay, G; Diamond, L; Thompson, D C et al. (1995) Nitric oxide. Role as a relaxant agonist and transmitter of nonadrenergic noncholinergic inhibitory nerves in guinea pig trachea. Chest 107:125S
Thompson, D C; Diamond, L; Altiere, R J (1992) Atypical presynaptic alpha-adrenoceptor modulation of neurally-mediated cholinergic responses in guinea-pig tracheal smooth muscle. Pulm Pharmacol 5:251-5
Altiere, R J; Diamond, L; Thompson, D C (1992) Omega-conotoxin-sensitive calcium channels modulate autonomic neurotransmission in guinea pig airways. J Pharmacol Exp Ther 260:98-103
Thompson, D C; Altiere, R J; Diamond, L (1990) Nicotinic agonist modulation of feline bronchomotor tone. Clin Exp Pharmacol Physiol 17:83-97
Thompson, D C; Diamond, L; Altiere, R J (1990) Presynaptic alpha adrenoceptor modulation of neurally mediated cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea. J Pharmacol Exp Ther 254:306-11
Thompson, D C; Diamond, L; Altiere, R J (1990) Enzymatic modulation of vasoactive intestinal peptide and nonadrenergic noncholinergic inhibitory responses in guinea pig tracheae. Am Rev Respir Dis 142:1119-23
Thompson, D C; Szarek, J L; Altiere, R J et al. (1990) Nonadrenergic bronchodilation induced by high concentrations of sulfur dioxide. J Appl Physiol 69:1786-91
Thompson, D C; Wells, J L; Altiere, R J et al. (1988) The effect of epithelium removal on non-adrenergic, non-cholinergic inhibitory responses in the isolated central airways of the cat and guinea pig. Eur J Pharmacol 145:231-7
Diamond, L; Altiere, R J; Thompson, D C (1988) The airway nonadrenergic noncholinergic inhibitory nervous system. Chest 93:1283-5

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