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

Article date: May 1993

By: L.A. Morrone, L. Romanelli, M.C. Amico, P. Valeri, in Volume 109, Issue 1, pages 48-52

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.

Naloxone (10−6m) did not elicit a response in preparations exposed to U‐50,488H (5 × 10−7 M‐2 × 10−6m). However, after exposure to U‐50,488H (5 × 10−7m), naloxone (10−6m) produced a strong contracture if the agonist was washed out 1 min before the addition of the antagonist.

The addition of naloxone (10−6m) to the ileum preparation exposed to U‐50,488H (10−7m or lower) caused a response of similar intensity irrespective of whether the agonist had been washed out.

The selective κ‐opioid antagonist, nor‐binaltorphimine (2.7 × 10−9m and 2.7 × 10−7m), injected before the opioid agonists, prevented the naloxone‐induced contracture after exposure to U‐50,488H (8 × 10−8m) but did not affect the contracture after exposure to morphine (5 × 10−7m).

Nor‐binaltorphimine (2.7 × 10−9m) caused a contraction of the ileum preparation when injected

min after exposure to U‐50,488H (8 × 10−8m) but not after morphine (5 × 10−7m).

The α2‐adrenoceptor agonist, clonidine (3 × 10−8m) and the calcium channel blocker, nifedipine (3 × 10−8m), injected 1 min before naloxone, blocked the ileum contraction to naloxone after exposure to U‐50,488H (8 × 10−8m). 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.

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.

Naloxone (10−6m) did not elicit a response in preparations exposed to U‐50,488H (5 × 10−7 M‐2 × 10−6m). However, after exposure to U‐50,488H (5 × 10−7m), naloxone (10−6m) produced a strong contracture if the agonist was washed out 1 min before the addition of the antagonist.

The addition of naloxone (10−6m) to the ileum preparation exposed to U‐50,488H (10−7m or lower) caused a response of similar intensity irrespective of whether the agonist had been washed out.

The selective κ‐opioid antagonist, nor‐binaltorphimine (2.7 × 10−9m and 2.7 × 10−7m), injected before the opioid agonists, prevented the naloxone‐induced contracture after exposure to U‐50,488H (8 × 10−8m) but did not affect the contracture after exposure to morphine (5 × 10−7m).

Nor‐binaltorphimine (2.7 × 10−9m) caused a contraction of the ileum preparation when injected

min after exposure to U‐50,488H (8 × 10−8m) but not after morphine (5 × 10−7m).

The α2‐adrenoceptor agonist, clonidine (3 × 10−8m) and the calcium channel blocker, nifedipine (3 × 10−8m), injected 1 min before naloxone, blocked the ileum contraction to naloxone after exposure to U‐50,488H (8 × 10−8m). 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.

DOI: 10.1111/j.1476-5381.1993.tb13529.x

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