Counting Bungarotoxin Binding Sites of Nicotinic Acetylcholine Receptors in Mammalian Cells with High Signal/Noise Ratios

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

Download Full-text

[3H]nicotine binding sites are associated with mammalian optic nerve terminals

Visual Neuroscience ◽

10.1017/s0952523800001504 ◽

1988 ◽

Vol 1 (2) ◽

pp. 245-248 ◽

Cited By ~ 34

Author(s):

Glen T. Prusky ◽

Max S. Cynader

Keyword(s):

Optic Nerve ◽

Visual System ◽

Nicotinic Acetylcholine Receptors ◽

Binding Sites ◽

Acetylcholine Receptors ◽

Optic Tract ◽

Nerve Fibers ◽

Nerve Terminals ◽

Nicotinic Acetylcholine ◽

Retinotectal Transmission

AbstractThe autoradiographic distribution of [3H]nicotine binding sites was examined in the superior colliculus in normal rats and cats, and in animals in which one or both eyes were removed. [3H]Nicotine binding sites in normal animals were densely concentrated in the superficial layers of the colliculus corresponding to the zone of termination of optic nerve fibers. Following bilateral enucleation, [3H]nicotine binding in the superficial collicular layers was drastically reduced. Unilateral enucleation markedly reduced [3H]nicotine binding sites in the colliculus contralateral to the removed eye, with little effect on the ipsilateral colliculus. These results provide further evidence that nicotinic acetylcholine receptors have a presynaptic location on optic tract terminals and may therefore modulate retinotectal transmission in both the rat and cat visual system.

Download Full-text

The Oncogenic Functions of Nicotinic Acetylcholine Receptors

Journal of Oncology ◽

10.1155/2016/9650481 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 29

Author(s):

Yue Zhao

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Mammalian Cells ◽

Acetylcholine Receptors ◽

Association Studies ◽

Nicotine Addiction ◽

Signal Pathways ◽

Genome Wide Association Studies ◽

Nicotinic Acetylcholine ◽

Lung Cancers ◽

Numerous Cell

Nicotinic acetylcholine receptors (nAChRs) are ion channels that are expressed in the cell membrane of all mammalian cells, including cancer cells. Recent findings suggest that nAChRs not only mediate nicotine addiction in the brain but also contribute to the development and progression of cancers directly induced by nicotine and its derived carcinogenic nitrosamines whereas deregulation of the nAChRs is observed in many cancers, and genome-wide association studies (GWAS) indicate that SNPs nAChRs associate with risks of lung cancers and nicotine addiction. Emerging evidences suggest nAChRs are posited at the central regulatory loops of numerous cell growth and prosurvival signal pathways and also mediate the synthesis and release of stimulatory and inhibitory neurotransmitters induced by their agonists. Thus nAChRs mediated cell signaling plays an important role in stimulating the growth and angiogenic and neurogenic factors and mediating oncogenic signal transduction during cancer development in a cell type specific manner. In this review, we provide an integrated view of nAChRs signaling in cancer, heightening on the oncogenic properties of nAChRs that may be targeted for cancer treatment.

Download Full-text