Interaction between calcium and ligand-binding sites of the purified acetylcholine receptor studied by use of a fluorescent lanthanide

Rübsamen, Helga; Hess, George P.; Eldefrawi, Amira T.; Eldefrawi, Mohyee E.

doi:10.1016/0006-291x(76)90009-7

Cited by 61 publications

(14 citation statements)

References 23 publications

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“…It has also been found that cardiac damage may be independent of the extent of AChE inhibition contrary to the high level inhibition of AChE in acute poisoning. Since acetylcholine receptors have a high binding capacity for calcium ions (38), the disorder of cellular morphology may be ascribed to a massive influx of Ca 2+ into the cytoplasm. The results also signify that TS even after two weeks has a potential to raise triglyceride levels, cause myocyte injury and subsequent myocardial injury.…”

Section: Discussionmentioning

confidence: 99%

Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study

Nurulain

Shafiullah

Yasin

et al. 2016

Archives of Industrial Hygiene and Toxicology

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Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under nondiabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD 50 ) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBCAChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition.

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Section: Discussionmentioning

confidence: 99%

Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study

Nurulain

Shafiullah

Yasin

et al. 2016

Archives of Industrial Hygiene and Toxicology

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“…Zinc ions, for instance, modulate the responses of GABAA (Draghun et al, 1990;Smart et al, 1994) and glycine (Laube et al, 1995) receptors to their neurotransmitter. In addition, calcium ions bind to several sites on nicotinic receptors (Chang and Neumann, 1976;Rubsamen et al, 1976aRubsamen et al, ,b, 1978Fairclough et al, 1986) and exert distinct effects on channel properties (Mulle et al, 1992b;Vemino et al, 1994;Amador and Dani, 1995) or on the regulation of channel activation (Mulle et al, 1992a;Vernino et al, 1992;Eisele et al, 1993;Amador and Dani, 1995) and desensitization (Cohen et al, 1974;Heidmann and Changeux, 1979).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, an analysis of the functional a7-V201-5HT3 chimera (Eisele et al, 1993), containing the N-terminal domain of the chick nicotinic a7 receptor subunit (Couturier et al, 1990) joined to the corresponding C-terminal part of the serotonergic 5-hydroxytryptamine (5HT3) receptor (Maricq et al, 1991), reveals that the chimera, like the a7 nicotinic receptor, is potentiated by Ca2+, whereas the 5HT3 receptor is not. Calcium (II) and the fluorescent lanthanide terbium (III), Tb3+, bind to Torpedo nicotinic receptors (Chang and Neumann, 1976;Rubsamen et al, 1976a,b;Fairclough et al, 1986) at sites that resist hydrolysis and are thought to be carried by short polypeptide sequences (Rubsamen et al, 1976a(Rubsamen et al, ,b, 1978 tentatively assumed to be analogous to those of the metal binding sites present in calcium binding proteins (Persechini et al, 1989;Strynadka and James, 1989;Falke et al, 1994). Calcium (II) and the fluorescent lanthanide terbium (III), Tb3+, bind to Torpedo nicotinic receptors (Chang and Neumann, 1976;Rubsamen et al, 1976a,b;Fairclough et al, 1986) at sites that resist hydrolysis and are thought to be carried by short polypeptide sequences (Rubsamen et al, 1976a(Rubsamen et al, ,b, 1978 tentatively assumed to be analogous to those of the metal binding sites present in calcium binding proteins (Persechini et al, 1989;Strynadka and James, 1989;Falke et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor.

et al. 1996

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The divalent cation calcium potentiates the physiological response of neuronal nicotinic receptors to agonists by enhancing ionic current amplitudes, apparent agonist affinity and cooperativity. Here we show that mutations in several consensus Ca2+ binding sequences from the N‐terminal domain of the neuronal alpha 7 nicotinic acetylcholine receptor alter Ca2+ potentiation of the alpha 7‐V201–5HT3 chimera. Mutations E18Q or E44Q abolish calcium‐enhanced agonist affinity but preserve the calcium increase of plateau current amplitudes and cooperativity. On the other hand, mutations of amino acids belonging to the 12 amino acid canonical domain (alpha 7 161–172) alter all features of potentiation by enhancing (D163, S169), reducing (E161, S165, Y167) or abolishing (E172) calcium effects on ionic current amplitudes and agonist affinity. Introduction of the alpha 7 161–172 domain in the calcium insensitive 5‐hydroxytryptamine (5HT3) serotoninergic receptor results in a receptor activated by 5HT and potentiated by calcium. In vitro terbium fluorescence studies with an alpha 7 160–174 peptide further show that mutation E172Q also alters in vitro calcium binding. Data are consistent with the occurrence of distinct categories of regulatory calcium binding sites, among which the highly conserved (alpha 7 161–172) domain may simultaneously contribute to calcium and agonist binding.

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“…There have been several investigations of the binding of divalent cations to the receptor purified from Torpedo electric organs (25,68,(115)(116)(117). Eldefrawi et al found that large amounts of calcium ions are bound to the receptor (115).…”

Section: Ligand Binding and Receptor Functioningmentioning

confidence: 99%

Physical Chemistry of Excitable Biomembranes

Neumann¹,

Bernhardt²

1977

Annu. Rev. Biochem.

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Interaction between calcium and ligand-binding sites of the purified acetylcholine receptor studied by use of a fluorescent lanthanide

Cited by 61 publications

References 23 publications

Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study

Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study

Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor.

Physical Chemistry of Excitable Biomembranes

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