Indirect evidence from a few recent studies indicates that histamine, serotonin, prostaglandins, acetylcholine and catecholamines may profoundly alter bronchomotor tone by modulating neurotransmitter release via prejunctional receptors on parasympathetic and sympathetic nerve varicosities. We propose to use superfusion techniques in order to obtain direct evidence for presynaptic modulation of neurotransmitter release in isolated canine airways. The effects of various endogenous substances on spontaneous release during basal conditions and on release during nerve stimulation will be investigated. Our findings may have important implications with respect to the normal regulation of bronchomotor tone as well as regulation during disease states when the local environment of nerve terminals may be substantially altered by the release of endogenous substances from surrounding cells. Byssinosis is a disease of textile workers that is characterized by reversible narrowing of airways. We have identified two compounds in aqueous extracts of cotton bracts that may cause bronchoconstriction by mechanisms other than those presently held accountable for this disease. One small molecular weight compound causes powerful contractions of dog, cat, and baboon airways by activating 5-HT receptors. Another compound, a condensed tannin, causes both the release of 5-HT and ADP from platelets and aggregation of these platelets. Both of these events may result in bronchoconstriction. We propose to isolate and identify the bronchoactive and platelet active factors and to determine their mechanism of action. These compounds might well be important in the pathogenesis of byssinosis and characterization of their mechanisms of action could foster new approaches to the management of this disease. Autoantibodies to Beta2-adrenergic receptors have recently been identified in the serum of patients with allergic rhinitis and asthma. We propose to investigate the effect of this antibody on Beta receptor function in canine airways.
| Russell, J A; Bishop, B P; Hyatt, R E (1987) Discharge of abdominal muscle alpha and gamma motoneurons during expiratory loading in cats. Exp Neurol 97:179-92 |
| Russell, J A; Simons, E J (1985) Modulation of cholinergic neurotransmission in airways by enkephalin. J Appl Physiol 58:853-8 |
| Russell, J A; Kircher, K W (1985) Metabolism of norepinephrine during nerve stimulation in dog trachea. J Appl Physiol 59:1236-41 |
