TACHYKININS AND REFLEXLY EVOKED ATROPINE-RESISTANT MOTILITY IN THE GUINEA-PIG COLON INVIVO

Distension of a balloon placed in the proximal colon of anesthetized, guanethidine- and naloxone-pretreated guinea pigs elicited a series of long-lasting regular phasic pressure waves which were suppressed by h examethonium. Activity evoked by a low degree of balloon distension wa s largely, but not completely, suppressed by atropine. Further balloon distension in atropine-treated animals enabled us to study the effect of tachykinin receptor antagonists on the atropine-resistant and hexa methonium-sensitive response to distension. The selective tachykinin r eceptor antagonists, (+/-)-CP 96,345 for the NK-1 receptor and L 659,8 77, MEN 10,376 and SR 48,968 for the NK-2 receptor. inhibited with var ying potency the atropine-resistant response to distension. These anta gonists also blocked the contraction of the guinea pig colon produced by the i.v. administration of selective NK-1 and NK-2 receptor agonist s. In vitro experiments. using mucosa-free circular muscle strips from the guinea pig colon, proved the existence of functional NK-1 and NK- 2 receptors in this tissue. We conclude that both NK-1 and NK-2 recept ors participate in the atropine-resistant reflex contractions produced by localized balloon distension of the guinea pig colon in vivo.