Muscarinic control of airway function.
Muscarinic M1, M2, and M3 receptor subtypes have been shown to be involved in the pre- and postjunctional control of airway diameter of various species, including man. In a guinea pig model of allergic asthma, the prejunctional M2 receptor was shown to become dysfunctional already during the early allergic reaction, thereby contributing to exaggerated vagal reflex activity and airway hyperreactivity. Moreover, a deficiency of endogenous nitric oxide was observed after allergen provocation, which may also contribute to an enhanced postjunctional M3 receptor-mediated cholinergic response. Both in human and in animal airway preparations it was shown that enhanced cholinergic contractions are relatively resistent to beta-adrenoceptor-mediated relaxation. The reduced beta-adrenoceptor function may primarily be due to transductional cross-talk between PI metabolism and adenylyl cyclase, including protein kinase C-induced uncoupling of the beta-adrenoceptor from the effector system. Cross-talk between postjunctional M2 receptor-mediated inhibition and beta-adrenoceptor-induced activation of adenylyl cyclase appears to be of minor functional importance, but could be enhanced in allergic asthma due to increased expression of the inhibitory G protein as induced by cytokines.
Zaagsma
J
J
Department of Molecular Pharmacology, University Centre for Pharmacy, Groningen, The Netherlands.
Roffel
A F
AF
Meurs
H
H
D000818:Animals; D001980:Bronchi / Q000502:physiology*; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000209:etiology; D009119:Muscle Contraction; D010716:Phosphatidylinositols / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology*; D015398:Signal Transduction; D014132:Trachea / Q000502:physiology*
D010716:Phosphatidylinositols; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic