title: A1-adenosine acute withdrawal response and cholecystokinin-8 induced contractures are regulated by Ca(2+)- and ATP-activated K(+) channels.
abstract: In isolated guinea-pig ileum (GPI), the A1-adenosine acute withdrawal response is under the control of several neuronal signalling systems, including the μ/κ-opioid and the cannabinoid CB1 systems. It is now well established that after the stimulation of the A1-adenosine system, the indirect activation of both μ/κ-opioid and CB1 systems is prevented by the peptide cholecystokinin-8 (CCk-8). In the present study, we have investigated the involvement of the Ca(2+)/ATP-activated K(+) channels in the regulation of both acute A1-withdrawal and CCk-8-induced contractures in the GPI preparation. Interestingly, we found that: (a) the A1-withdrawal contracture is inhibited by voltage dependent Ca(2+)-activated K(+) channels, Kv, while it is enhanced by the voltage independent Ca(2+)-activated K(+) channels, SKCa; (b) in the presence of CCk-8, the inhibitory effect of the A1 agonist, CPA, on the peptide induced contracture is significantly enhanced by the voltage independent Ca(2+)-activated K(+) channel, SKCa; and (c) the A1-withdrawal contracture precipitated in the presence of CCk-8 is controlled by the ATP-sensitive potassium channels, KATP. Our data suggest, for the first time, that both Ca(2+)- and ATP-activated K(+) channels are involved in the regulation of both A1-withdrawal precipitated and CCk-8 induced contractures.
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cascio
authors.affiliation: Department of Human Physiology and Pharmacology 'Vittorio Erspamer', University of Rome "La Sapienza", Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Valeri
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Tucker
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. Electronic address: p.marini@abdn.ac.uk.
authors.forename: Pietro
authors.initials: P
authors.lastname: Marini
mesh_terms: 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* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D054086:KATP Channels; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D043682:Receptor, Adenosine A1; D011957:Receptors, Opioid; C410885:cholecystokinin 8; D002766:Cholecystokinin
keywords: A1-acute withdrawal; A1-adenosine receptor; Adenosine triphosphate-activated potassium channels; Calcium-activated potassium channels; Cholecystokinin-8; Guinea-pig ileum