Abstract

MISLE, AJ et al. G-Protein-Dependent Antagonists Binding In M3 mAchR from Tracheal Smooth Muscle. AVFT [online]. 2001, vol.20, n.2, pp.143-151. ISSN 0798-0264.

The M3 and M2 mAchR subtypes were located in plasma membranes fractions from bovine tracheal smooth muscle (BTSM). Native mAchRs from BTSM were studied by using [3H]QNB binding. Receptor heterogeneity was expressed for muscarinic agonists and antagonists being the high affinity states sensitive to GTPgS. We showed that GTPgS effects seem to be mediated by PTX sensitive Gi/o proteins. Antagonist mAchR heterogeneity towards 4-DAMP (M3) and pirenzepine (M1) was detected. However, M2 antagonists as methoctramine and AF-DX 116 did not show such responses either in the presence or absence of GTPgS. Through 4-DAMP alkylation of the M3 mAchR subtype, a M2 subtype prevailed, which exhibits GTPgS-dependent agonist binding whereas antagonist binding was GTPgS-insensitive. Thus, antagonists binding receptor heterogeneity here described is due to the M3 mAchR subtype showing two affinity states, one being regulated by Gi/o-proteins.

Keywords : Muscarinic agonists; Muscarinic antagonists; Pertussis toxin; GTPgS; Tracheal smooth muscle.