• Our data support the interaction of α-CTx RgIA at the α10/α9 rather than the α9/α10 nAChR subunit interface, and may facilitate the development of selective ligands with therapeutic potential. (aspetjournals.org)
  • Bionomics has a long-standing collaboration with MSD to identify novel α7 nAChR PAMs suitable for the treatment of cognitive disorders that address the limitations seen with nAChR agonists, such as lack of selectivity against related ligand-gated ion channels, desensitization of the receptor with sustained exposure, and an inverted U-shaped dose response function," said Spyros Papapetropoulos, M.D., Ph.D., President and CEO of Bionomics. (bionomics.com.au)
  • Activation of nicotine/nAChR signaling is associated with lung cancer risk and drug resistance. (tmu.edu.tw)
  • We focused on nAChR pathways activated by nicotine and its downstream signaling involved in regulating apoptotic factors of mitochondria and drug resistance in lung cancer. (tmu.edu.tw)
  • The nAChR subtype mediating nicotine-induced dilation in isolated porcine basilar arterial rings denuded of endothelium was therefore examined pharmacologically and immunohistochemically. (aspetjournals.org)
  • Results from using an in vitro tissue bath technique indicated that relaxation induced by nicotine (100 μM) was blocked by preferential α 7 -nAChR antagonists (methyllycaconitine and α-bungarotoxin) and nonspecific nAChR antagonist (mecamylamine) in a concentration-dependent manner, but was not affected by dihydro-β-erythroidine (a preferential α 4 -nAChR antagonist). (aspetjournals.org)
  • BERTRAND, D. Functional interactions of varenicline and nicotine with nAChR subtypes implicated in cardiovascular control. (bvsalud.org)
  • However, mutations of these residues had little or no effect on toxin block of the α9α10 nAChR. (aspetjournals.org)
  • In contrast, mutations of homologous residues in the opposing nAChR subunits (α10 Ε197, P200 and α9 T61, D121) resulted in 19- to 1700-fold loss of toxin activity. (aspetjournals.org)
  • Researchers are searching for other genetic changes, including mutations in other subunits of nAChR, that may underlie the condition. (medlineplus.gov)
  • We previously showed that α-conotoxin (CTx) RgIA, one of the few α9α10 selective ligands identified to date, is 300-fold less potent on human vs. rat α9α10 nAChR. (aspetjournals.org)
  • The original lead molecule BNC375, a Type I α7 nAChR PAM, showed a robust and sustained dose-dependent efficacy over a broad dose range and across multiple cognitive animal models. (bionomics.com.au)
  • This result suggested that activation of α7 nAChR partially reversed the expression level of PSD95 protein in the hippocampus of APP/PS1_DT mice. (aging-us.com)
  • In some cases, a gene other than those that make up the nAChR are involved. (medlineplus.gov)
  • Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. (nih.gov)
  • The CHRNA4 gene provides instructions for making one part (subunit) of a larger protein called a neuronal nicotinic acetylcholine receptor (nAChR). (medlineplus.gov)
  • Both influx of calcium through the α 7 nicotinic acetylcholine receptor (nAChR) channel as well as the binding of intracellular G proteins were involved in the effect of PNU120596 on intracellular calcium. (aspetjournals.org)
  • of a larger protein called a neuronal nicotinic acetylcholine receptor (nAChR). (nih.gov)
  • However, the specific neuronal nicotinic acetylcholine receptor (nAChR) subtypes responsible for these effects are not clearly understood. (nih.gov)
  • [ 1 , 2 ] Although the chief target of the autoimmune attack in most cases is the skeletal muscle nicotinic acetylcholine receptor (nAChR), other antigenic targets that are components of the neuromuscular junction (NMJ) have also been implicated. (medscape.com)
  • To date, 11 members of the neuronal nAChR family have been identified and cloned from vertebrate genomes (for review, see Lindstrom, 1996 ). (jneurosci.org)
  • Of the nine different nAChR subunits identified in the mammalian brain, the homomeric α 7 nAChR ( α 7) is one of the most abundant, present in both neuronal and non-neuronal cells and expressed in regions of the brain such as the hippocampus and cortex. (aspetjournals.org)
  • NMR structures of the alpha7 nAChR transmembrane domain. (nih.gov)
  • Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) for alpha4beta2 nAChR subtype. (nih.gov)
  • Each nAChR protein is made up of a combination of five subunits, usually two alpha (α) and three beta (β) subunits. (medlineplus.gov)
  • Many different combinations are possible, and the characteristics of each nAChR protein depend on which subunits it contains. (medlineplus.gov)
  • In the brain, nAChR proteins most commonly consist of two α4 subunits and three β2 subunits. (medlineplus.gov)
  • Because nicotine exerts its effects on the brain primarily by interacting with nAChR channels, researchers have studied the subunits of these channels to see if genetic changes influence tobacco dependence. (medlineplus.gov)
  • Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants. (nih.gov)
  • Association of nAChR gene haplotypes with heavy alcohol use and body mass. (cdc.gov)
  • CHRNA4 mutations make nAChR channels more sensitive to the neurotransmitter acetylcholine, allowing the channels to open more easily than usual. (medlineplus.gov)
  • Cigarettes and other forms of tobacco contain nicotine, a drug that interacts with nAChR channels in the brain to produce a feeling of heightened well-being and alertness. (medlineplus.gov)
  • These results suggest a functional dissociation between nAChR neural substrates within the VTA that mediate the bivalent motivational properties of nicotine and further suggest that nicotine may produce its motivational effects through a glutamatergic mechanism. (nih.gov)
  • Taken together, these behavioral indicators of nAChR activation suggest that in mixtures, neonicotinoids could interfere with nAChR signaling despite their low affinity for the nAChR. (frontiersin.org)
  • In preclinical models, pathogenic nAChR variants cause a gain of function mutation with sensitivity to acetylcholine antagonists and agonists. (nih.gov)
  • The presence of the inactivating mutation was established by polymerase chain reaction and genomic sequencing, and the lack of α4 nAChR function was confirmed in primary fibroblasts isolated from the α4 KO mice. (nih.gov)
  • The nAChR channel opens in response to the binding of agonist (activation) but also becomes refractory to activation in the course of prolonged exposure to nicotinic agonists (desensitization). (jneurosci.org)
  • Our results show that BDNF, acting on the tyrosine kinase TrkB receptor, induces a rapid decrease of α7 nAChR-mediated responses in hippocampal interneurons of the CA1 stratum radiatum. (jneurosci.org)