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

Pietro Marini, Luca Romanelli, Daniela Valeri, Paolo Tucci, Maura Palmery

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 A1-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.
Original languageEnglish
Pages (from-to)622-632
Number of pages11
JournalJournal of Pharmacy and Pharmacology
Volume62
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • acute withdrawl
  • adenosine A1-receptor
  • cholecystokinin
  • guinea-pig ileum
  • indirect activation
  • opioid receptor

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