The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in anesthetized guinea pigs. Guinea pigs were injected intraperitoneally with saline (control group) or ovalbumin (10 mg/kg) on days 1, 3, and 5. One group of sensitized animals was challenged on days 20-25 with aerosolized ovalbumin for 5 min/day (challenged group), while another group of the sensitized animals was not challenged (sensitized group). On day 26 the animals were anesthetized, paralyzed, tracheostomized, and artificially ventilated. Pulmonary inflation pressure (Ppi), 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 Ppi) and bradycardia. In the control group, pilocarpine (1-100 μg/kg iv) 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 iv) produced a marked potentiation of vagally induced bronchoconstriction. These results confirm previous findings. In the challenged guinea pigs, pilocarpine did not inhibit vagally induced bronchoconstriction. Furthermore, gallamine did not potentiate vagally induced bronchoconstriction to the same degree as in the controls. In the group of animals that was sensitized but not challenged, the potentiation of vagally induced bronchoconstriction by gallamine was identical to the controls. There was no increase in baseline Ppi in the sensitized or challenged animals compared with the controls. In the heart, gallamine inhibited vagally induced bradycardia equally in both groups of animals, indicating that, in antigen-challenged animals, changes in M2- receptor function on parasympathetic nerves in the lungs are not part of a generalized decrease in M2-receptor function. These results demonstrate that M2-muscarinic receptor-mediated inhibition of acetylcholine release from parasympathetic nerves in the lungs is not altered in sensitized animals but is decreased in sensitized animals that have been challenged with antigen. Loss of this inhibition would result in increased release of acetylcholine from the parasympathetic nerves and may explain airway hyperresponsiveness after antigen challenge.
- airway resistance
- neuromodulator receptors
- parasympathetic nervous system
- respiratory hyperreactivity
- respiratory hyperresponsiveness
ASJC Scopus subject areas
- Physiology (medical)