TACHYKININ NK1 AND NK2 RECEPTORS MEDIATE THE NONCHOLINERGIC BRONCHOSPASTIC RESPONSE TO CAPSAICIN AND VAGAL-STIMULATION IN GUINEA-PIGS

1 The antibronchospastic activity against acetylcholine, capsaicin, el ectrical vagal stimulation and the selective tachykinin agonists ([bet a Ala(8)]NKA-(4-10) and [Sar(9)]SP sulfone) of a novel NK2 receptor an tagonist, MEN10,627 and/or the known NK1 receptor antagonist (+/-)-CP9 6,345 was studied in anaesthetized guinea-pigs. 2 MEN10,627 (0.1 mu mo l kg(-1) i.v.) and(+/-)-CP96,345 (3 mu mol kg(-1) i.v.) selectively re duced the bronchospasm induced by NK2 and NK1 tachykinin receptor agon ists, respectively, without affecting the other tachykinin receptor ag onist- or acetyl-choline-induced bronchospastic response. 3 MEN10,627 (0.1-3 mu mol kg(-1) i.v.), in a dose-dependent manner, reduced the no n-cholinergic response induced by bilateral stimulation of the vagi or by intravenous capsaicin. 4 The administration of(+/-)-CP96,345 (3 mu mol kg(-1) i.v.) alone did not affect these responses but, when admin istered in association with the NK2 antagonist, (+/-)-CP96,345, was ab le to potentiate its inhibitory effect. 5 It is concluded that both NK 1 and NK2 receptors are involved in the non-cholinergic bronchoconstri ction induced by capsaicin or by stimulation of the vagi, although the NK2 receptor contribution is prominent.