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


RESULTS
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.
Marini
Pietro
P
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. p.marini@abdn.ac.uk
Romanelli
Luca
L
Valeri
Daniela
D
Tucci
Paolo
P
Valeri
Pacifico
P
Palmery
Maura
M
D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology*
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D011957:Receptors, Opioid; D018047:Receptors, Purinergic P1; C410885:cholecystokinin 8; D002766:Cholecystokinin