Inhibitory effect of hemicholinium-3 on presynaptic nicotinic acetylcholine receptors located on the terminal region of myenteric motoneurons

2006 ◽  
Vol 49 (4) ◽  
pp. 327-333 ◽  
Author(s):  
Péter Mandl ◽  
János P. Kiss
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Inhibitory Effect ◽  
Terminal Region ◽  
Nicotinic Acetylcholine

scholarly journals Molecular Regulation of α3β4 Nicotinic Acetylcholine Receptors by Lupeol in Cardiovascular System

2020 ◽  
Vol 21 (12) ◽  
pp. 4329
Author(s):  
Sanung Eom ◽  
Chaelin Kim ◽  
Hye Duck Yeom ◽  
Jaeeun Lee ◽  
Shinhui Lee ◽  
...  
Keyword(s):  
Natural Products ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Animal Experiments ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Nicotinic Acetylcholine ◽  
Electrode Voltage ◽  
Treatment Of Hypertension ◽  
Nicotine Acetylcholine Receptor

Cardiovascular disease (CVD) occurs globally and has a high mortality rate. The highest risk factor for developing CVD is high blood pressure. Currently, natural products are emerging for the treatment of hypertension to avoid the side effects of drugs. Among existing natural products, lupeol is known to be effective against hypertension in animal experiments. However, there exists no study regarding the molecular physiological evidence against the effects of lupeol. Consequently, we investigated the interaction of lupeol with α3β4 nicotinic acetylcholine receptors (nAChRs). In this study, we performed a two-electrode voltage-clamp technique to investigate the effect of lupeol on the α3β4 nicotine acetylcholine receptor using the oocytes of Xenopus laevis. Coapplication of acetylcholine and lupeol inhibited the activity of α3β4 nAChRs in a concentration-dependent, voltage-independent, and reversible manner. We also conducted a mutational experiment to investigate the influence of residues of the α3 and β4 subunits on lupeol binding with nAChRs. Double mutants of α3β4 (I37A/N132A), nAChRs significantly attenuated the inhibitory effects of lupeol compared to wild-type α3β4 nAChRs. A characteristic of α3β4 nAChRs is their effect on transmission in the cardiac sympathetic ganglion. Overall, it is hypothesized that lupeol lowers hypertension by mediating its effects on α3β4 nAChRs. The interaction between lupeol and α3β4 nAChRs provides evidence against its effect on hypertension at the molecular-cell level. In conclusion, the inhibitory effect of lupeol is proposed as a novel therapeutic approach involving the antihypertensive targeting of α3β4 nAChRs. Furthermore, it is proposed that the molecular basis of the interaction between lupeol and α3β4 nAChRs would be helpful in cardiac-pharmacology research and therapeutics.

scholarly journals Cysteine [2,4] Disulfide Bond as a New Modifiable Site of α-Conotoxin TxIB

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 119
Author(s):  
Baojian Zhang ◽  
Maomao Ren ◽  
Yang Xiong ◽  
Haonan Li ◽  
Yong Wu ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Therapeutic Agent ◽  
Inhibitory Effect ◽  
The Other ◽  
Nicotinic Acetylcholine ◽  
Exploitation And Utilization ◽  
Orthogonal Protection ◽  
Activity Loss

α-Conotoxin TxIB, a selective antagonist of α6/α3β2β3 nicotinic acetylcholine receptor, could be a potential therapeutic agent for addiction and Parkinson’s disease. As a peptide with a complex pharmacophoric conformation, it is important and difficult to find a modifiable site which can be modified effectively and efficiently without activity loss. In this study, three xylene scaffolds were individually reacted with one pair of the cysteine residues ([1,3] or [2,4]), and iodine oxidation was used to form a disulfide bond between the other pair. Overall, six analogs were synthesized with moderate isolated yields from 55% to 65%, which is four times higher than the traditional two-step oxidation with orthogonal protection on cysteines. The cysteine [2,4] modified analogs, with higher stability in human serum than native TxIB, showed obvious inhibitory effect and selectivity on α6/α3β2β3 nicotinic acetylcholine receptors (nAChRs), which was 100 times more than the cysteine [1,3] modified ones. This result demonstrated that the cysteine [2,4] disulfide bond is a new modifiable site of TxIB, and further modification can be a simple and feasible strategy for the exploitation and utilization of α-Conotoxin TxIB in drug discovery.

Nicotinic acetylcholine receptors in the patients with Parkinson's disease: 5IA-SPECT

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S586-S586 ◽  
Author(s):  
Kazuo Hashikawa ◽  
Hidefumi Yoshida ◽  
Nobukatsu Sawamoto ◽  
Shigetoshi Takaya ◽  
Chihiro Namiki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine
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