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.