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

Abstract

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 mu-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 A(1)-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.