Disease relevance of Bromoacetylcholine

• Since the neuroblastoma-inoculated A/J mice are considered to be comparable to human neuroblastoma, the cytolytic action of bromoacetylcholine and bromoacetate on murine neuroblastoma warrants further studies on patients [1].
• Among all cholinergic blockers tested, only the irreversible cholinergic blockers such as bromoacetylcholine (BrACh), iodoacetylcholine and alphabungarotoxin were effective to inhibit glioma cells (with 50% cytolytic doses of 6.7 x 10(-6)M, 3.0 x 10(-6)M and 7.4 x 10(-5)M respectively) [2].

High impact information on Bromoacetylcholine

• Analysis of the deuterium lineshape obtained at various temperatures from unoriented nAcChoR membranes labeled with deuterated bromoacetylcholine (BAC) showed that the quaternary ammonium group of the ligand is well constrained within the agonist binding site when compared with the dynamics observed in the crystalline solids [3].
• Two classes of agonist binding sites, in the ratio of 4:1 for PC12 cell BgtRs and 3:1 for alpha7/5HT3 BgtRs, were revealed by bromoacetylcholine alkylation of the reduced sites on both PC12 BgtRs and alpha7/5HT3 BgtRs [4].
• Reoxidation takes place at the disulfide located near the nicotinic receptor agonist binding site, inasmuch as reoxidation by these agents prevents affinity alkylation by bromoacetylcholine, and occupation by the competitive antagonist d-tubocurarine prevents reoxidation [5].
• In keratinocyte cell cultures, bromoacetylcholine stopped cell division [6].
• Reduction of the receptor significantly decreased the binding of three of the monoclonal antibodies, but subsequent alkylation with N-ethylmaleimide or the affinity labeling reagent bromoacetylcholine had no additional effect on binding [7].

Anatomical context of Bromoacetylcholine

• Evidence for spare nicotinic acetylcholine receptors and a beta 4 subunit in bovine adrenal chromaffin cells: studies using bromoacetylcholine, epibatidine, cytisine and mAb35 [8].
• Both of these [125I]KBgT binding sites are blocked following pre-treatment of ganglia with the irreversible nicotinic affinity agent bromoacetylcholine [9].
• Stoichiometry of the ligand-binding sites in the acetylcholine-receptor oligomer from muscle and from electric organ. Measurement by affinity alkylation with bromoacetylcholine [10].
• Bromoacetylcholine and acetylcholinesterase introduced via liposomes into motor nerve endings block increases in quantal size [11].
• In enzymatically isolated mucosal cells of rat tracheas, a considerable ChAT activity (21 nmol.mg protein 1.h-1) was detected, blockable by bromoacetylcholine [12].

Associations of Bromoacetylcholine with other chemical compounds

• The nicotinic receptor affinity reagent bromoacetylcholine irreversibly blocks high-affinity toxin binding to PC12 cell membranes that have been treated with dithiothreitol [13].
• After application of the alkylating agent bromoacetylcholine (2 or 100 microM, with 2 microM neostigmine), dithiobis(nitrobenzoic acid) could no longer restore nicotinic function. d-Tubocurarine (300 microM) equally protected against alkylation with bromoacetylcholine (2 microM) after dithiothreitol (2 mM) or NTX treatment [14].
• Treatment of neuroblastoma in mice with bromoacetylcholine and bromoacetate [1].
• Furthermore, the neuroblastoma inhibitory effect of bromoacetylcholine was not affected by atropine [15].
• Since the choline acetyltransferase inhibitor, dimethylaminoethyl chloroacetate, does not inhibit neuroblastoma efficiently in vitro, the potent cytolytic action of bromoacetylcholine is probably not due to its choline acetyltransferase inhibitory action [15].

Gene context of Bromoacetylcholine

• Thus, in HUVEC cultures, ChAT activity amounted to 0.78 +/- 0.15 nmol x mg protein(-1) x h(-1) (n = 3), but was only partially (about 50%) inhibited by the ChAT inhibitor bromoacetylcholine (30 microM) [16].
• Enzymatically isolated human mucosa contained a rather low ChAT-like activity (0.5 nmol.mg protein 1.h-1), not sensitive to bromoacetylcholine [12].
• This 600-fold higher affinity for the receptor than found from physiological studies [Kact congruent to 10 micrometers; Karlin, A. (1973) Fed. Proc. Fed. Am. Soc. Exp. Biol. 32, 1847--1853] can be attributed to a ligand-induced affinity change of the membrane-bound receptor upon preincubation with bromoacetylcholine [17].
• Cytolytic effects of bromoacetylcholine on neuroblastoma in vitro [18].
• ACh synthesis was not inhibited by bromoacetylcholine, a specific inhibitor of choline acetyltransferase (ChAT) [19].

Analytical, diagnostic and therapeutic context of Bromoacetylcholine

• We find that the inhibitory response persists after treatment of the neurons with 1 mM DTT, even if the reduction is followed by alkylation of the receptor with bromoacetylcholine to prevent possible reformation of disulfide bonds [20].
• The nicotinic acetylcholine receptor from Discopyge tschudii electroplax was purified by affinity chromatography on Affi-Gel 401 using bromoacetylcholine as the ligand [21].
• The activity of choline acetyltransferase (ChAt; E.C. 2.3.1.6) measured as the bromoacetylcholine-sensitive portion of the maximal rate of acetylcholine synthesis has been determined in homogenates of nine regions of the heart of control rats and rats sacrificed 72-74 h after bilateral cervical vagotomy [22].

References