Activation of inward current associated with M-potassium current inhibition in m1-muscarinic receptor-transformed NG108-15 cells by KST-5452, a novel cognition enhancer.
The electrophysiological effects of KST-5452 [3-(m-phenoxybenzylidene)-quinuclidine], an M1 muscarinic acetylcholine receptor (muscarinic AChR) binding compound, were studied in NG108-15 neuroblastoma x glioma hybrid cells transfected with m1 muscarinic AChR cDNA. Application of KST-5452 to m1-transformed NGPM1-27 cells elicited a sustained inward current associated with decreased conductance and reduced M-current relaxations at a holding potential of -20 mV. The KST-5452-induced responses were blocked by pirenzepine, suggesting that KST-5452 acts as a potent excitant via M1 muscarinic AChRs in brain neurons.
Kishida
H
H
Biochemical Research Laboratories, Kaneka Corporation, Takasago, Japan.
Yamamoto
K
K
Fuse
Y
Y
Noda
M
M
Higashida
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001597:Benzylidene Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002461:Cell Line, Transformed; D003071:Cognition / Q000187:drug effects*; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D010890:Pirenzepine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011812:Quinuclidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D001597:Benzylidene Compounds; C089332:KST 5452; D015221:Potassium Channels; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D000109:Acetylcholine