Withdrawal contractures of guinea-pig isolated ileum after acute activation of kappa-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 kappa-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 kappa-opioid receptors. 2. Naloxone (10(-6) M) did not elicit 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 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 kappa-opioid antagonist, nor-binaltorphimine (2.7 x 10(-9) M and 2.7 x 10(-7) M), injected before the opioid agonists, prevented the naloxone-induced contracture after exposure to U-50,488H (8 x 10(-8) M) but did not affect the contracture after exposure to morphine (5 x 10(-7) M). 5. Nor-binaltorphimine (2.7 x 10(-9) M) caused a contraction of the ileum preparation when injected 5 min after exposure to U-50,488H (8 x 10(-8) M) but not after morphine (5 x 10(-7) M). 6. The alpha 2-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 naloxone after exposure to U-50,488H (8 x 10-8 M). The results demonstrate that the stimulation of Kappa-opioid receptors can induce a similar dependence in guinea-pig ileum to that produced by activation of micro receptors.
Institute of Pharmacology and Pharmacognosy, University of Rome La Sapienza, Italy.
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Morrone
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Romanelli
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Amico
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Valeri
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D009543:Nifedipine; D003000:Clonidine