Tachykinin NK2 receptors and enhancement of cholinergic transmission in the inflamed rat colon: an in vivo motility study

1 In the gastrointestinal tract, tachykinin NK2 receptors are localized bot h on smooth muscle and nerve fibres. NK2 receptor antagonists reduce exagge rated intestinal motility in various diarrhoea models but the site of actio n contributing to this effect is unknown. In this study we investigated the effects of atropine (1.4 mu mol kg(-1), i.v.), hexamethonium (13.5 mu mol kg(-1), i.v.), and nepadutant (0.1 mu mol kg(-1), i.v.), a selective tachyk inin NK2 receptor antagonist, on distension (0.5 and 1 ml)-, or irritation (acetic acid, 0.5 ml of 7.5% v v(-1))-induced motility in the rat distal co lon in vivo. The effects of atropine, hexamethonium or N-(' ())-nitro-L-arg ininemethylester (L-NAME, 1.85 mu mol kg(-1), i.v.) on [beta Ala(8)]NKA(4-1 0) (10 nmol kg(-1), i.v.)-induced colonic contractions were also investigat ed. 2 When the colonic balloon was filled with a subthreshold volume (0.5 ml), the intraluminal instillation of acetic acid triggered a high-amplitude pha sic colonic motility which was partially reduced by nepadutant and suppress ed by either hexamethonium or atropine. Filling of the balloon with 1 ml ev oked reflex (hexamethonium-sensitive), atropine-sensitive phasic colonic mo tility: nepadutant had no significant effect on the distension-evoked motil ity. 3 Neither hexamethonium nor atropine significantly reduced [beta Ala(8)]NKA (4-10)-induced colonic contractions, whereas nepadutant suppressed them. Fo llowing L-NAME pretreatment, [beta Ala(8)]NKA(4-10)-induced colonic contrac tions were inhibited by both atropine and hexamethonium. In hexamethonium-p retreated animals, an atropine-sensitive component of [beta Ala(8)]NKA(4-10 )-induced colonic contractions was also evident. 4 These results indicate that the application of irritants onto the colonic mucosa induces the release of endogenous tachykinins which enhance excitat ory cholinergic mechanisms through the stimulation of NK2 receptors.