Acute withdrawal induced by adenosine A1-receptor activation in isolated guinea-pig ileum: Role of opioid receptors and effect of cholecystokinin

Objectives In isolated guinea-pig ileum, the μ-opioid acute withdrawal response is under control of several neuronal systems, including the κ-opioid and the A1-adenosine systems, which are involved in the μ-withdrawal response inhibitory control. After μ-opioid system stimulation, indirect activation of both κ-opioid and A 1-adenosine systems is prevented by the peptide cholecystokinin-8 (CCk-8). Guinea-pig ileum exposed to A1-adenosine agonist (CPA), shows a withdrawal contracture precipitated by the A1-adenosine antagonist (CPT). We investigated this response. Methods We investigated the involvement of the opioid system in the A1-adenosine acute withdrawal response in guinea-pig ileum, the potential induced cross-dependence between the A1 and the opioid system and also the interaction between the CCk-8 and A1 systems. Key findings We found that in the guinea-pig ileum preparation exposed to CPA, μ- and κ-opioid antagonists increased the withdrawal response to CPT. Tissues exposed to CPA showed a contractile response to the opioid receptor antagonist naloxone only after complete removal of the A1-agonist. In the presence of CPA, the response to CCk-8 was inhibited while a significant increase in CPT response intensity was observed. Conclusions In guinea-pig ileum, stimulation of the A1 system indirectly activates both μ- and κ-opioid systems; this indirect activation is significantly, albeit not completely, antagonised by CCk-8. Cross dependence between A1 and opioid systems was also observed. © 2010 Royal Pharmaceutical Society of Great Britain.