Possible role of potassium channels in mu-receptor-mediated inhibition and muscarinic autoinhibition in acetylcholine release from myenteric plexus of guinea pig ileum.
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-aminopyridine (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.
Nishiwaki
H
H
Department of Veterinary Pharmacology, College of Agriculture, Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai, Japan.
Saitoh
N
N
Nishio
H
H
Takeuch
T
T
Hata
F
F
D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000145:classification / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
D000701:Analgesics, Opioid; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001030:Apamin; D009270:Naloxone; D019789:Tetraethylammonium; D009020:Morphine; C064719:iberiotoxin; D001285:Atropine; D015761:4-Aminopyridine; D000109:Acetylcholine; D005905:Glyburide