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

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 μg 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 incrase 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 bronchconstriction 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 parainfluenze virus. Loss of this inhibition would result in increased release of acetylcholine from the parasympathetic nerves and may explain virus-induced airway hyperresponsiveness.