Pharmacological characterization of muscarinic receptors in the contractions of isolated bronchi in the horse

We investigated the effects of nonselective muscarinic antagonist (atropine) and of selective muscarinic subtype 1 (M₁), 2 (M₂), 3 (M₃) antagonists (VU0255035, methoctramine, pFHHSiD, respectively) on the contractions evoked by electrical field stimulation (EFS) or by exogenous ACh in isolated horse bronchial muscle. Atropine completely inhibited neurogenic contractions in a concentration‐dependent fashion, whereas selective muscarinic antagonists induced relevant modifications only at the highest concentration tested. Experiments with selective muscarinic antagonists in combination showed that only the simultaneous blockade of M₁/M₃ or M₂/M₃ receptors was able to induce a nearly complete suppression of contractions. The contractions induced by exogenous ACh were competitively antagonized only by atropine (pA₂ = 9.01 ± 0.05). M₃ selective antagonist, up to 10⁻⁶ m , caused a moderate concentration‐dependent rightward shift of ACh curve (pA₂ = 7.96 ± 0.10). These data show that M₃ muscarinic receptors possess a central role in mediating cholinergic contraction of horse bronchi, while M₁ and M₂ receptors seem to have a cooperative role. Selective muscarinic antagonists seem unlikely to be useful against bronchoconstriction associated with airway diseases in horses. Conversely, compounds with selectivity for both M₁ and M₃ receptors could be as effective as traditional anticholinergics and induce fewer cardiac side effects.