One characteristic feature of asthma and chronic bronchitis is an extreme sensitivity of the airways to a large number of physical and pharmacological stimuli. These stimuli set off a chain of events resulting in the constriction of the airways. The fact that atropine dilates the airways of some patients suggests that activity in the vagal motor pathway is elevated and possibly that endogenous substances, released from the lung in asthma and pulmonary anaphylaxis, alter transmission in airway ganglia. contributing to increased smooth muscle tone and mucous gland secretion. However, we will not understand how the alternations in the autonomic nervous system lead to chronic disease of the airway until we understand the basic electrophysiology and morphology of its nerves and ganglion cells. In this study, we propose to systematically investigate these electrical and morphological properties. Since the upper and lower airmways respond to stimuli in a similar fashion, we propose to concentrate this investigation on the trachea, where nerves and ganglion cells are more accessible to study. First, we will examine the structure of nerves and ganglion cells comprising the tracheal plexus. We will examine ganglion cells stained for acetylcholinesterase, identify catecholamine-containing elements and sensory neurons, and determine the distribution of mast cells. Next, we will impale ganglion cells from all areas of the tracheal plexus and determine passive and active properties and responses to vasoactive intestinal peptide, substance P, histamine, and bradykinin, and other substances that are likely modulators of ganglionic transmission. Finally, we will label individual cells with horseradish peroxidase or lucifer yellow and examine the cell's soma, dentrites, and axons. Our experiments will be carried out in the cat and ferret using the isolated tracheal segment preparation and using staining, recording and labeling techniques that have already proven successful in our previous studies. Thus, we propose to make a detailed study of neurons innervating trachael smooth muscles and mucuous glands, examining both morphology and electrophysiology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL027319-05
Application #
3339084
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1982-01-01
Project End
1988-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143