Role of K+ channels in the expression of dependence by A1 receptor-stimulationin guinea pig ileum (GPI)

Aim: In previous works we have seen that the A1 adenosine acute withdrawal response in GPI is controlled by indirectly activated opioid system leading to a cross-dependence. In the present study we aimed to see if 4-AP and TEA , known inhibitors of K+ channels could: a) Increase the GPI precipitated contractions when administrated with a selective adenosine A1-receptor agonist, b) Determine a contraction to the adenosine A1-receptor antagonist, CPT in naive preparations Methods: The experimental procedure was that used by Valeri et al., (Neuropharmacology, 1996). After a first CPA/CPT test (CPA; 2.9x10-9 M: CPT; 4x10-7 M), GPI preparations were exposed for 5 min to CPA and then challenged with 4-AP (1-4 mM) or TEA (60-240 mM), and 5 min later, with CPT. In subsequent tests the m- and k-opioid antagonist NL (5.4x 10-7M) and BNI (3.4x10-8 M) were added before CPT. In naive GPI preparations 4-AP and TEA were injected before CPT and then before or after NL and BNI. Results: Administrated after or without CPA, 4-AP and TEA increased in a dose-related way the contractile response to CPT. Administration of BNI/NL/CPT after the highest dose of 4-AP elicited a strong contraction to BNI, but not increase the ones to the other antagonists. Conclusion: The K+ channels can play an important role in the expression of dependence, probably due to the ability of these K+ channel blockers to unmasking the constitutive activity of adenosine A1, m- and k-opioid receptor antagonists