Ballati L, Evangelista S, Maggi C A, Manzini S
Pharmacology Department, Istituto Farmacobiologico Malesci S.p.A., Firenze, Italy.
Eur J Pharmacol. 1992 Apr 22;214(2-3):215-21. doi: 10.1016/0014-2999(92)90121-j.
Bronchospasm induced by i.v. injection of equieffective doses of acetylcholine, capsaicin or selective tachykinin receptor agonists ([Sar9]SP sulfone or [beta-Ala8]neurokinin A (NKA-4-10)) (for NK1 and NK2 receptors, respectively) was studied in anaesthetized guinea-pigs. The NK1 and NK2 receptor antagonists, (+/-)-CP96,345 (3 mumol/kg i.v.) and MEN 10,376 (3 mumol/kg i.v.), selectively abolished the bronchoconstriction induced by the respective agonist, showing that both NK1 and NK2 receptors mediate bronchoconstriction in guinea-pig airways and that they are activated independently. Capsaicin-induced bronchospasm was inhibited by atropine (1.5 mumol/kg i.v.) and MEN 10,376 (3 mumol/kg i.v.), but unaffected by (+/-)-CP96,345 (3 mumol/kg i.v.). Hexamethonium (79 mumol/kg i.v.), propranolol (17 mumol/kg i.v.) and physostigmine (0.9 mumol/kg i.v.) enhanced the airway constriction induced by acetylcholine, capsaicin, [Sar9]SP sulfone or [beta-Ala8]NKA-(4-10) while guanethidine (67 mumol/kg s.c. for two days) increased only bronchoconstriction induced by capsaicin or the selective NK2 receptor agonist. In hexamethonium-treated animals, MEN 10,376 still abolished the increase in insufflation pressure induced by [beta-Ala8]NKA-(4-10) and reduced the increase elicited by capsaicin. In summary, in anaesthetized guinea pig i.v. capsaicin-induced bronchospasm through activation of postjunctional NK2 (but not NK1) receptors along with activation of cholinergic pathways. This motor response is moderated by the simultaneous stimulation of a sympathetic bronchodilating mechanism(s), possibly through activation of NK2 receptors localized in sympathetic ganglia.
在麻醉的豚鼠中，研究了静脉注射等效剂量的乙酰胆碱、辣椒素或选择性速激肽受体激动剂（分别为[Sar9]SP砜或[β - Ala8]神经激肽A（NKA - 4 - 10），针对NK1和NK2受体）所诱发的支气管痉挛。NK1和NK2受体拮抗剂，（±）- CP96,345（静脉注射3 μmol/kg）和MEN 10,376（静脉注射3 μmol/kg），分别选择性地消除了由相应激动剂诱发的支气管收缩，表明NK1和NK2受体均介导豚鼠气道的支气管收缩，且它们是独立激活的。辣椒素诱发的支气管痉挛被阿托品（静脉注射1.5 μmol/kg）和MEN 10,376（静脉注射3 μmol/kg）抑制，但不受（±）- CP96,345（静脉注射3 μmol/kg）影响。六甲铵（静脉注射79 μmol/kg）、普萘洛尔（静脉注射17 μmol/kg）和毒扁豆碱（静脉注射0.9 μmol/kg）增强了乙酰胆碱、辣椒素、[Sar9]SP砜或[β - Ala8]NKA -（4 - 10）所诱发的气道收缩，而胍乙啶（皮下注射67 μmol/kg，连续两天）仅增加了辣椒素或选择性NK2受体激动剂所诱发的支气管收缩。在六甲铵处理的动物中，MEN 仍然消除了由[β - Ala8]NKA -（4 - 10）诱发的吹入压力增加，并减少了由辣椒素引起的增加。总之，在麻醉的豚鼠中，静脉注射辣椒素通过激活节后NK2（而非NK1）受体以及胆碱能途径诱发支气管痉挛。这种运动反应可能通过激活位于交感神经节的NK2受体，同时刺激交感支气管舒张机制而得到调节。
