Effect of 4-amynopyridine (4AP) and tetraethylamonium (TEA) on the expression of u-opioid acute dependence in guinea pig ileum

Aim: In guinea pig ileum (GPI) the naloxone (NL) precipitated with drawal contraction after a brief exposure to ?-opioid agonists is under the inhibitory control of endogeneous activated systems as k-opioid, adenosine A1, cannabinoid CB1, probably due to the opening of K+ channels. In the present study we aimed to see if 4AP and TEA, known inhibitors of k+ channels, could 1) increase the GPI precipitated contractions when administrated after a ?-opioid agonist dermorphin (D), and 2) prevent the development of dependence when administered before D. Methods: The experimental procedure was that used by Valeri P. et al. (Neuropharmacology 35:377-384, 1996) The GPI prepartions were exposed for 5 min to D (6.10-9M) and then challenged with NL (5,4.10-7 M). In subsequent tests 4AP (1-4 ?M) or TEA (60-360 ?M) were injected 10-5 min. before or 5 min. after D and then with NL. Results: 4AP and TEA increased the amplitude contractions to NL in a dose related way and increased the percentage of responding preparations when injected 10-5 min before or 5min after D. Both 4AP and TEAcontracted the GPI in a dose related way, showing great variability between tissue preparations. These contractions were atropine-and tetrodotoxin-sensitive and under the inhibiting control of the systems that inhibited the NL precipitated contractions. Conclusion: These results indicate that the block by TEA and 4AP of K+ channels overtakes the inhibitory control of endogenous activated systems, but these are poorly influenced by these K+ channel blockers, a behaviour similar that has been observed with the excitatory peptide cholecystokinin.