Is There Loss of a Protective Muscarinic Receptor Mechanism in Asthma: Conclusion

Is There Loss of a Protective Muscarinic Receptor Mechanism in Asthma: ConclusionContractile actions of histamine are mediated directly via stimulation of Hx-histamine receptors on airway smooth muscle and, in part, indirectly via stimulation of vagal reflex causing release of acetylcholine at the parasympathetic nerve endings. Inhibition of histamine-induced bronchoconstriction by the anticholinergic agent, ipratropium bromide, in our normal subjects is consistent with this concept. Thus, it is possible that suppression of histamine-induced bronchoconstriction by prior methacholine exposure in normal subjects may be mediated via prejunctional inhibitory muscarinic receptors. It is interesting to note that muscarinic receptor blockade with ipratropium and muscarinic receptor stimulation with methacholine caused an equivalent suppression of histamine-induced bronchoconstriction. The inhibitory action of prior methacholine stimulation on histamine-induced bronchoconstriction was observed after the bronchoconstrictor action of methacholine had dissipated, suggesting that compared to bronchoconstrictor muscarinic receptors (possibly Mx and M3 subtypes) the duration of stimulation of inhibitory muscarinic receptors (possibly M2-subtype) is of a much longer period. buy glucophage online

Our results are consistent with the recent observations of Minette et al who studied the effects of prior muscarinic receptor stimulation with pilocarpine on subsequent bronchoconstrictor responses to SOs, an agent known to cause bronchoconstriction via cholin-efgic reflex. In normal subjects, pretreatment with pilocarpine and not histamine inhibited the S02-induced bronchoconstriction, whereas in the asthmatic group pilocarpine failed to inhibit the bronchoconstrictor effects of S02. Based upon their data, these authors also concluded the presence of feed-back inhibitory muscarinic receptors in normal airway and postulated a defect of these receptors in asthmatic airways.
The clinical significance of this finding is not clear. In normal subjects, it may represent a protective role of the cholinergic system at the level of inhibitory muscarinic receptors, which may modulate local regulation of airway smooth muscle tone. A lack of this suppressive action of muscarinic stimulation in asthmatic subjects may represent the absence of this protective mechanism, which leads us to hypothesize a loss of the inhibitory muscarinic receptor (“autoreceptor”) mechanism in bronchial asthma.


Category: Asthma

Tags: Asthma, Methacholine, muscarinic receptor