WITHDRAWAL CONTRACTURES OF GUINEA-PIG ISOLATED ILEUM AFTER ACUTE ACTIVATION OF KAPPA-OPIOID RECEPTORS

The present study was undertaken to investigate firstly whether a brie f exposure for 5 min of guinea-pig isolated ileum to the kappa-opioid agonist, U-50,488H produced a withdrawal contracture on addition of na loxone and secondly to ascertain whether the response was due to the a ctivation of kappa-opioid receptors. Naloxone (10(-6) M) did not elici t a response in preparations exposed to U-50,488H (5 x 10(-7) M-2 x 10 (-6) M). However, after exposure to U-50,488H (5 x 10(-7) M), naloxone (10(-6) M) produced a strong contracture if the agonist was washed ou t 1 min before the addition of the antagonist. The addition of naloxon e (10(-6) M) to the ileum preparation exposed to U-50,488H (10(-7)) M or lower) caused a response of similar intensity irrespective of wheth er the agonist had been washed out. The selective K-opioid antagonist, nor-binaltorphimine (2.7 x 10(-9) M and 2.7 x 10(-7) M), injected bef ore the opioid agonists, prevented the naloxone-induced contracture af ter exposure to U-50,488H (8 x 10(-8) M) but did not affect the contra cture after exposure to morphine (5 x 10(-7) M). Nor-binaltorphimine ( 2.7 x 10(-9) M) caused a contraction of the ileum preparation when inj ected 5 min after exposure to U-50,488H (8 x 10(-8) M) but not after m orphine (5 x 10(-7) M). The alpha2-adrenoceptor agonist, clonidine (3 x 10(-8) M) and the calcium channel blocker, nifedipine (3 x 10(-8) M) , injected 1 min before naloxone, blocked the ileum contraction to nal oxone after exposure to U-50,488H (8 x 10(-8) M). The results demonstr ate that the stimulation of kappa-opioid receptors can induce a simila r dependence in guinea-pig ileum to that produced by activation of mu receptors.