Nicotinic receptor channel

Keyser KT, Britto ERG, Schoepfer R, Whiting P Cooper J, Conroy W, Brozozowska-Prechtl A, Karten HJ, Lindstrom J (1993) Three subtypes of a-bungarotoxin-sensitive nicotinic acetylcholine receptors are expressed in chick brain. J Neurosci 13 442-452 Khiroug S, Harkness PC, Lamb PW, Sudweeks S, Khiroug L, Millar NS, Yakel JL (2002) Rat nicotinic ACh receptor al and fil subunits co-assemble to form functional heteromeric nicotinic receptor channels. J Physiol 540 425 34... 

Acetylcholine release. Policosanol produced some interactions in the modulation of the acetylcholine (ACh) release at the mouse neuromuscular junction. Policosanol enhanced to a small extent either the spontaneous or the evoked ACh release. An increase in the rate of the conformational change induced at the nicotinic receptor-channel complex by ACh was also observed L... 

The skin of neotropical frogs of the Dendrobatidae family has been a rich source of bioactive compounds [42] such as the alkaloids epibatidine, batrachotoxins, histrionicotoxin, and indolizidines. The latter have been investigated due to their activity as noncompetitive blockers of the nicotinic receptor channels [43]. Because only small amounts are available and due to their pronounced physiological activity, these alkaloids are important targets for organic synthesis [44]. Since... 

Myasthenia gravis is an autoimmune disease affecting skeletal muscle neuromuscular junctions. In this disease, antibodies are produced against the main immunogenic region found on subunits of the nicotinic receptor-channel complex. 

Yang X, Kuo Y, Devay P, Yu C, Role L. 1998. A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogen-esis. Neuron 20 255-270. 

The pharmacological activity of decahydroquinoline ci5-195A and analogs in neuromuscular preparations appears to involve noncompetitive blockade both of nicotinic receptor-channels and of voltage-dependent sodium and potassium channels (see reviews in Refs. 3 and 5). Recently, both cis- and rra/i5-decahydroquinolines were shown to block ion flux through nicotinic receptor channels in pheochromocytoma cells and to enhance the rate of desensitization of such nicotinic channels (64,82). 

There have been no studies on the biological activity of the above quinolizidine alkaloids. It is expected that they, like the 5,8-disubstituted indolizidines and other lipophilic dendrobatid alkaloids, will be noncompetitive blockers of nicotinic receptor-channels. 

Disubstituted piperidines (and piperideines) from ants have insecticidal activity and, as venom constituents, serve the ant in a defensive, repellant function (149). 2,6-Disubstituted piperidines are potent noncompetitive blockers of nicotinic receptor-channels in neuromuscular preparations (162) and in electric eel electroplax (163). Synthetic 241D was a potent noncompetitive blocker of nicotinic receptor-channels in both electric eel electroplax and pheochromocytoma cells (64). 

Konopka LM, Neel DS, Parsons RL. Clindamycin-induced alteration of ganglionic function. II. Effect of nicotinic receptor-channel function. Brain Res 1988 458(2) 278-84. 

The biological activity of class A alkaloids as non-competitive blockers for nicotinic receptor-channels has been known for years [5] and the attention has now turned to the biological activity of class B alkaloids. 

Granja R, Femandez-Fernandez JM, Izaguirre V, Gonzalez-Garcia C, Cena V. Omega-agatoxin FVA blocks nicotinic receptor channels in bovine chromaffin cells. FEES Lett 1995 362(l) 15-8. 

A radioactive perhydro-derivative of histrionicotoxin (pH]H,2-HTX (10, 92) has proved a very useful tool for investigation of the binding sites for histrionicotoxin in membranes and microsacs from Torpedo electroplax preparations (see Table 12 for references). Its use has not been extended to muscle preparations where the density of nicotinic receptor channel complexes are many fold lower than in Torpedo electroplax. Indeed, no specific binding could be detected in the electroplax of the Egyptian electric fish (Malapterurus electricus) where the density of nicotinic receptors also appear very low (97). In membranes from Torpedo electroplax pH]Hi2-HTX binds to a site with an affinity constant (Kd) of about 0.4 pM. The density of the binding sites for pH]Hi2 HTX is apparently about twice that of the acetylcholine-binding sites in electroplax membranes. The rate of... 

---