Inhibitory control of the acute mu-withdrawal response by indirectly activated adenosine A1 and kappa-opioid systems in the Guinea-pig ileum; reversal by cholecystokinin.
In the isolated guinea-pig ileum (GPI), the acute mu-opioid withdrawal response is inhibited by the kappa-opioid system, indirectly activated by the opioid agonist; yet, other inhibitory mechanisms are probably operating. On the other hand, cholecystokinin (CCK-8) strongly enhances the withdrawal response. In this study, we have shown that the adenosine A1 antagonist 8-cyclopenthyl-1,3-dimethylxantine (CPT) increased the withdrawal response in dermorphin/naloxone (NLX) tests but lacked any effect if the withdrawal tests were carried out in presence of CCK-8. In tissue preparations coming from a same animal both CPT and the kappa-opioid antagonist, nor-binaltorphimine (BNI), increased the intensity of the withdrawal responses; the effects of the two antagonists were additive. The intensity of withdrawal contractile responses in presence of CCK-8 was similar to those obtained in presence of the two antagonists. Tissue preparations tested with dermorphin/CCK-8/NLX and then washed out yielded contractile responses when subsequently challenged with CPT, BNI or BNI+CPT, with a percentage markedly higher than the percentage of the response to NLX challenge. BNI+CPT also increased the intensity of the response to NLX challenge. These data suggest that acute exposure of GPI to dermorphin induces the activation of both the adenosine A1 and kappa-opioid systems, which in turns inhibit the mu-withdrawal response. CCK-8 antagonises the inhibitory effect of the indirectly activated systems.
Romanelli
Luca
L
Dipartimento di Fisiologia Umana e Farmacologia Vittorio Erspamer, Università di Roma La Sapienza, P.le A. Moro, 5-00185 Rome, Italy. luca.romanelli@uniroma1.it
Morrone
Luigi Antonio
LA
Amico
Maria Carmela
MC
Palmery
Maura
M
Tucci
Paolo
P
Valeri
Pacifico
P
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D043682:Receptor, Adenosine A1; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C030058:dermorphin; C053907:8-cyclopentyl-1,3-dimethylxanthine; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D002766:Cholecystokinin; D013806:Theophylline