Acute withdrawal induced by adenosine A_1-receptor activation in isolated guinea-pig ileum: role of opioid receptors and effect of cholecystokinin

摘要

Objectives In isolated guinea-pig ileum, the mu-opioid acute withdrawal response is under control of several neuronal systems, including the kappa-opioid and the A_1-adenosine systems, which are involved in the mu-withdrawal response inhibitory control. After /i-opioid system stimulation, indirect activation of both kappa-opioid and A_1-adenosine systems is prevented by the peptide cholecystokinin-8 (CCk-8). Guinea-pig ileum exposed to A_1-adenosine agonist (CPA), shows a withdrawal contracture precipitated by the Ai-adenosine antagonist (CPT). We investigated this response. Methods We investigated the involvement of the opioid system in the A_1-adenosine acute withdrawal response in guinea-pig ileum, the potential induced cross-dependence between the A_1 and the opioid system and also the interaction between the CCk-8 and A_1 systems. Key findings We found that in the guinea-pig ileum preparation exposed to CPA, mu- and kappa-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 A_1-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 A_1 system indirectly activates both mu- and kappa-opioid systems; this indirect activation is significantly, albeit not completely, antagonised by CCk-8. Cross dependence between A_1 and opioid systems was also observed.