Possible role of potassium channels in mu-receptor-mediated inhibition andmuscarinic autoinhibition in acetylcholine release from myenteric plexus of guinea pig ileum

It is known that mu-agonists inhibit electrical field stimulation (EFS)-evo ked ACh release from longitudinal muscle myenteric plexus (LMMP) preparatio n of guinea pig ileum when muscarinic autoinhibition does not fully work. I n the present study, the possible role of K+ channels in the mechanisms of mu-agonists-induced inhibition and autoinhibition of ACh release was studie d. In the presence of atropine, which blocks the autoinhibition, non-select ive K+ channel blockers, tetraethylammonium (TEA) and 4-aminopyridine (4-AP ), reversed the inhibitory effect of mu-agonists, morphine and [D-Ala(2), N -Me-Phe(4), Gly(5)-ol] enkephalin, on EFS-evoked ACh release, but not that of kappa-agonist U-50,488. Apamin, iberiotoxin or glibenclamide did not aff ect the inhibition of ACh release by morphine. On the other hand, in the ab sence of atropine (under the autoinhibition working condition), 4-AP increa sed EFS-evoked ACh release, but atropine did not further increase ACh relea se in the presence of 4-AP. In contrast, although TEA did not affect EFS-ev oked ACh release, atropine increased ACh release in the presence of TEA. Th ese results suggest that the inhibitory effects of mu-agonists and muscarin ic autoinhibition on the ACh release are associated with activation of diff erent 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 as sociated with 4-AP- but not TEA-sensitive K+ channels.