Tachykinin NK1 and NK2 receptors mediate the non‐cholinergic bronchospastic response to capsaicin and vagal stimulation in guinea‐pigs

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Abstract
1. The antibronchospastic activity against acetylcholine, capsaicin, electrical vagal stimulation and the selective tachykinin agonists ([beta Ala8]NKA-(4-10) and [Sar9]SP sulfone) of a novel NK2 receptor antagonist, MEN10,627 and/or the known NK1 receptor antagonist (+/-)-CP96,345 was studied in anaesthetized guinea-pigs. 2. MEN10,627 (0.1 mumol kg-1 i.v.) and (+/-)-CP96,345 (3 mumol kg-1 i.v.) selectively reduced the bronchospasm induced by NK2 and NK1 tachykinin receptor agonists, respectively, without affecting the other tachykinin receptor agonist- or acetylcholine-induced bronchospastic response. 3. MEN10,627 (0.1 mumol kg-1 i.v.), in a dose-dependent manner, reduced the non-cholinergic response induced by bilateral stimulation of the vagi or by intravenous capsaicin. 4. The administration of (+/-)-CP96,345 (3 mumol kg-1 i.v.) alone did not affect these responses but, when administered in association with the NK2 antagonist, (+/-)-CP96,345, was able to potentiate its inhibitory effect. 5. It is concluded that both NK1 and NK2 receptors are involved in the non-cholinergic bronchoconstriction induced by capsaicin or by stimulation of the vagi, although the NK2 receptor contribution is prominent.