Parainfluenza virus infection damages inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves in the guinea-pig.

Allison D Fryer,David B Jacoby

doi:10.1111/j.1476-5381.1991.tb12164.x

Abstract

1. The effect of viral infection on the function of neuronal M2 muscarinic autoreceptors in the lungs was studied in anaesthetized guinea-pigs. 2. Guinea-pigs were inoculated intranasally with either parainfluenza type 3 or with a vehicle control. Four days later the animals were anaesthetized, paralysed and artificially ventilated. Pulmonary inflation pressure, tidal volume, blood pressure, and heart rate were recorded. Both vagus nerves were cut and electrical stimulation of the distal portions caused bronchoconstriction (measured as an increase in pulmonary inflation pressure) and bradycardia. 3. In control animals, pilocarpine (1-100 micrograms kg-1, i.v.) attenuated vagally-induced bronchoconstriction by stimulating inhibitory M2 muscarinic receptors on parasympathetic nerves in the lungs. Conversely, blockade of these receptors with the antagonist gallamine (0.1-10 mg kg-1, i.v.) produced a marked potentiation of vagally-induced bronchoconstriction. These results confirm previous findings. 4. In guinea-pigs infected with parainfluenza virus, pilocarpine did not inhibit vagally-induced bronchoconstriction. Furthermore, gallamine did not potentiate vagally-induced bronchoconstriction to the same degree as in uninfected controls. 5. There was no increase in baseline pulmonary inflation pressure in the infected animals over the controls. Receptors on airway smooth muscle were unchanged by viral infection since large doses of pilocarpine caused equivalent bronchoconstriction in both groups of animals. Gallamine inhibited the vagally-induced fall in heart rate equally in both groups of animals indicating that virus-induced changes in M2 receptor function on pulmonary parasympathetic nerves are not part of a generalized decrease in M2 receptor function. 6. These results demonstrate that the M2 muscarinic receptor-mediated inhibition of acetylcholine release from parasympathetic nerves in the lungs is decreased in animals infected with parainfluenza virus. Loss of this inhibition would result in increased release of acetylcholine from the parasympathetic nerves and may explain virus-induced airway hyperresponsiveness.

Highlights

Viral infections of the lung exacerbate asthma in children and in adults (Frick et al, 1979; Henderson et al, 1979; Welliver, 1983; Little et al, 1978)
6 These results demonstrate that the M2 muscarinic receptor-mediated inhibition of acetylcholine release from parasympathetic nerves in the lungs is decreased in animals infected with parainfluenza virus
In control guinea-pigs, pilocarpine inhibited and gallamine potentiated bronchoconstriction elicited by electrical stimulation of the vagus nerves

Summary

Introduction

Viral infections of the lung exacerbate asthma in children and in adults (Frick et al, 1979; Henderson et al, 1979; Welliver, 1983; Little et al, 1978). In normal subjects viral infection of the lung produces temporary increases in baseline airways resistance (Johanson et al, 1969; Picken et al, 1972; Blair et al, 1976; Hall et al, 1976) and increases bronchial reactivity to a variety of stimuli (Aquilina et al, 1980; Empey et al, 1976; Little et al, 1978). These changes often persist for weeks beyond the period of clinical illness. The bronchoconstrictor response to aerosolized acetylcholine (ACh) is the same in guinea-pigs infected with parainfluenza virus as in sham-infected animals (Dusser et al, 1989)

Methods

Results

Conclusion