Ethanol-Nicotine Interactions at alpha-Bungarotoxin-Insensitive Nicotinic Acetylcholine Receptors in Rat Cortical Neurons

1999 ◽  
Vol 23 (3) ◽  
pp. 439-445 ◽  
Author(s):  
William Marszalec ◽  
Gary L. Aistrup ◽  
Toshio Narahashi
2001 ◽  
Vol 59 (4) ◽  
pp. 732-743 ◽  
Author(s):  
Takashi Mori ◽  
Xilong Zhao ◽  
Yi Zuo ◽  
Gary L. Aistrup ◽  
Kiyonobu Nishikawa ◽  
...  

2016 ◽  
Vol 310 (9) ◽  
pp. C748-C754 ◽  
Author(s):  
JianGang Wang ◽  
YaLi Wang ◽  
FangLi Guo ◽  
ZhiBo Feng ◽  
XiangFang Wang ◽  
...  

The roles of nicotine on Ca2+ oscillations [intracellular Ca2+ ([Ca2+]i) oscillation] in rat primary cultured cortical neurons were studied. The spontaneous [Ca2+]i oscillations (SCO) were recorded in a portion of the neurons (65%) cultured for 7–10 days in vitro. Application of nicotine enhanced [Ca2+]i oscillation frequency and amplitude, which were reduced by the selective α4β2-nicotinic acetylcholine receptors (nAChRs) antagonist dihydro-β-erythroidine (DHβE) hydrobromide, and the selective α7-nAChRs antagonist methyllycaconitine citrate (MLA, 20 nM). DHβE reduced SCO frequency and prevented the nicotinic increase in the frequency. DHβE somewhat enhanced SCO amplitude and prevented nicotinic increase in the amplitude. MLA (20 nM) itself reduced SCO frequency without affecting the amplitude but blocked nicotinic increase in [Ca2+]i oscillation frequency and amplitude. Furthermore, coadministration of both α4β2- and α7-nAChRs antagonists completely prevented nicotinic increment in [Ca2+]i oscillation frequency and amplitude. Thus, our results indicate that both α4β2- and α7-nAChRs mediated nicotine-induced [Ca2+]i oscillations, and two nAChR subtypes differentially regulated SCO.


Marine Drugs ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 49
Author(s):  
William Kem ◽  
Kristin Andrud ◽  
Galen Bruno ◽  
Hong Xing ◽  
Ferenc Soti ◽  
...  

Nereistoxin (NTX) is a marine toxin isolated from an annelid worm that lives along the coasts of Japan. Its insecticidal properties were discovered decades ago and this stimulated the development of a variety of insecticides such as Cartap that are readily transformed into NTX. One unusual feature of NTX is that it is a small cyclic molecule that contains a disulfide bond. In spite of its size, it acts as an antagonist at insect and mammalian nicotinic acetylcholine receptors (nAChRs). The functional importance of the disulfide bond was assessed by determining the effects of inserting a methylene group between the two sulfur atoms, creating dimethylaminodithiane (DMA-DT). We also assessed the effect of methylating the NTX and DMA-DT dimethylamino groups on binding to three vertebrate nAChRs. Radioligand receptor binding experiments were carried out using washed membranes from rat brain and fish (Torpedo) electric organ; [3H]-cytisine displacement was used to assess binding to the predominantly high affinity alpha4beta2 nAChRs and [125I]-alpha-bungarotoxin displacement was used to measure binding of NTX and analogs to the alpha7 and skeletal muscle type nAChRs. While the two quaternary nitrogen analogs, relative to their respective tertiary amines, displayed lower α4β2 nAChR binding affinities, both displayed much higher affinities for the Torpedo muscle nAChR and rat alpha7 brain receptors than their respective tertiary amine forms. The binding affinities of DMA-DT for the three nAChRs were lower than those of NTX and MeNTX. An AChBP mutant lacking the C loop disulfide bond that would potentially react with the NTX disulfide bond displayed an NTX affinity very similar to the parent AChBP. Inhibition of [3H]-epibatidine binding to the AChBPs was not affected by exposure to NTX or MeNTX for up to 24 hr prior to addition of the radioligand. Thus, the disulfide bond of NTX is not required to react with the vicinal disulfide in the AChBP C loop for inhibition of [3H]-epibatidine binding. However, a reversible disulfide interchange reaction of NTX with nAChRs might still occur, especially under reducing conditions. Labeled MeNTX, because it can be readily prepared with high specific radioactivity and possesses relatively high affinity for the nAChR-rich Torpedo nAChR, would be a useful probe to detect and identify any nereistoxin adducts.


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