Withdrawal contractures of guinea‐pig isolated ileum after acute activation of κ‐opioid receptors

1 The present study was undertaken to investigate firstly whether a brief exposure for 5 min of guinea‐pig isolated ileum to the κ‐opioid agonist, U‐50,488H produced a withdrawal contracture on addition of naloxone and secondly to ascertain whether the response was due to the activation of κ‐opioid receptors. 2 Naloxone (10 −6 m ) did not elicit a response in preparations exposed to U‐50,488H (5 × 10 −7 M‐2 × 10 −6 m ). However, after exposure to U‐50,488H (5 × 10 −7 m ), naloxone (10 −6 m ) produced a strong contracture if the agonist was washed out 1 min before the addition of the antagonist. 3 The addition of naloxone (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 whether the agonist had been washed out. 4 The selective κ‐opioid antagonist, nor‐binaltorphimine (2.7 × 10 −9 m and 2.7 × 10 −7 m ), injected before the opioid agonists, prevented the naloxone‐induced contracture after exposure to U‐50,488H (8 × 10 −8 m ) but did not affect the contracture after exposure to morphine (5 × 10 −7 m ). 5 Nor‐binaltorphimine (2.7 × 10 −9 m ) caused a contraction of the ileum preparation when injected 5 min after exposure to U‐50,488H (8 × 10 −8 m ) but not after morphine (5 × 10 −7 m ). 6 The α 2 ‐adrenoceptor agonist, clonidine (3 × 10 −8 m ) and the calcium channel blocker, nifedipine (3 × 10 −8 m ), injected 1 min before naloxone, blocked the ileum contraction to naloxone after exposure to U‐50,488H (8 × 10 −8 m ). The results demonstrate that the stimulation of K‐opioid receptors can induce a similar dependence in guinea‐pig ileum to that produced by activation of μ receptors.