Effects of calmodulin antagonists on sodium-dependent high-affinity choline uptake.
The effects of calmodulin (CaM) antagonists were investigated on the sodium-dependent high-affinity choline uptake (SDHACU) as assessed by the specific binding of [3H]hemicholinium-3 ([3H]HCh-3) and high-affinity [3H]choline uptake. Potassium depolarization caused a significant 2-fold increase in the specific binding of [3H]HCh-3 in slices of rat striatum in vitro. CaM antagonists, including trifluoperazine (TFP), W-5, W-7, promethazine and haloperidol, dose-dependently inhibited potassium depolarization-stimulated [3H]HCh-3 binding with IC50s of 20, 40, 70, 30 and 48 (microM), respectively. Scatchard analysis revealed that the inhibitory effect of TFP resulted from a decrease in Bmax but no change in Kd of [3H]HCh-3 binding. Potassium depolarization of slices also stimulated high-affinity [3H]choline uptake, which was completely inhibited by 10 microM TFP. These results are discussed in relation to the regulatory mechanisms of SDHACU.
Yamada
K
K
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Saltarelli
M D
MD
Coyle
J T
JT
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002794:Choline / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006426:Hemicholinium 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000502:physiology*
D002147:Calmodulin; D006426:Hemicholinium 3; D011189:Potassium Chloride; D012964:Sodium; D002794:Choline