Evidence for prejunctional muscarinic autoreceptors in human and guinea pig trachea.

• DOI: 10.1164/ajrccm.152.3.7663798
• Publication Date: 2013-04-04T21:53:27Z
• Authors: H J Patel; P J Barnes; T Takahashi; S Tadjkarimi; M H Yacoub; M G Belvisi
• Keywords: Methoctramine; Oxotremorine; Autoreceptor; Ipratropium bromide; Muscarinic antagonist

Functional studies suggest the presence of prejunctional muscarinic autoreceptors on cholinergic nerves in human airways. However, these are an indirect method evaluating changes neurally evoked acetylcholine (ACh) release. We have investigated and guinea pig trachea by comparing effects receptor antagonists pirenzepine (M1), methoctramine (M2), 4-DAMP (M3), rispenzepine (M1/M3) neural contractile responses electrical field stimulation (EFS) [3H]ACh The M1, M1/M3, or M3 inhibited EFS-evoked response a concentration-dependent manner (4-DAMP > pirenzepine), whereas facilitated this at low concentrations ( < 3 microM). In ACh release studies, antagonist had no significant effect, pirenzepine, methoctramine, significantly increased trachea. contrast, was agonist oxotremorine M. Methoctramine nonselective ipratropium bromide, but not antagonists, These data autoinhibitory nerve terminals addition, action bromide may limit its use treatment obstructive airways disease.