Possible Role of Potassium Channels in Mu-receptor-Mediated Inhibition and Muscarinic Autoinhibition in Acetylcholine Release From Myenteric Plexus of Guinea Pig Ileum

抄録

It is known that mu-agonists inhibit electrical field stimulation(EFS)-evoked ACh release from longitudinal muscle myenteric plexus(LMMP)preparation of guinea pig ileum when muscarinic autoinhibition does not fully work.In the present study, the possible role of K⁺ channels in the mechanisms of mu-agonists-induced inhibition and autoinhibition of ACh release was studied.In the presence of atropine, which blocks the autoinhibition, non-selective K⁺ channel blockers, tetraethylammonium(TEA)and 4-amino-pyridine(4-AP), reversed the inhibitory effect of mu-agonists, morphine and [D-Ala², N-Me-Phe⁴, Gly⁵-ol]enkephalin, on EFS-evoked ACh release, but not that of kappa-agonist U-50, 488.Apamin, iberiotoxin or glibenclamide did not affect the inhibition of ACh release by morphine.On the other hand, in the absence of atropine(under the autoinhibition working condition), 4-AP increased EFS-evoked ACh release, but atropine did not further increase ACh release in the presence of 4-AP.In contrast, although TEA did not affect EFS-evoked ACh release, atropine increased ACh release in the presence of TEA.These results suggest that the inhibitory effects of mu-agonists and muscarinic autoinhibition on the ACh release are associated with activation of different types of K⁺ channels in the guinea pig LMMP preparations:the former is associated with 4-AP- and TEA-sensitive K⁺ channels and the latter is associated with 4-AP- but not TEA-sensitive K⁺ channels.