Tachykinin NK1 and NK2 receptors mediate the non-cholinergic bronchospastic response to capsaicin and vagal stimulation in guinea-pigs.
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.
Boni
P
P
Pharmacology Departments, Istituto Farmacobiologico Malesci S.p.A., Firenze, Italy.
Ballati
L
L
Evangelista
S
S
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001986:Bronchial Spasm / Q000503:physiopathology*; D002211:Capsaicin / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D007327:Insufflation; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C062618:substance P, Sar(9)-Met(O2)(11)-; C064218:neurokinin A (4-10), beta-Ala(8)-; C090951:MEN 10627; D013373:Substance P; D015288:Neurokinin A; D002211:Capsaicin; C066892:CP 96345