Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands
Two new polypeptides were isolated and purified from the venom of the snake Dendroaspis angusticeps, which also contains other neuroactive peptides such as Dendrotoxins and Fasciculins. The amino acid composition of the peptides was determined and the first 10 amino acids from the MTX2 N-terminal fr...
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1992
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v20_n2_p237_Jerusalinsky http://hdl.handle.net/20.500.12110/paper_01970186_v20_n2_p237_Jerusalinsky |
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paper:paper_01970186_v20_n2_p237_Jerusalinsky |
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paper:paper_01970186_v20_n2_p237_Jerusalinsky2023-06-08T15:20:34Z Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands muscarinic receptor polypeptide snake venom toxin amino acid composition amino acid sequence animal cell article binding site brain cortex cattle competitive inhibition ligand binding nonhuman priority journal protein isolation rat synaptic membrane Amino Acids Animal Brain Stem Cattle Cell Membrane Cerebral Cortex Chromatography, Gel Chromatography, High Pressure Liquid Chromatography, Ion Exchange Elapid Venoms Kinetics Muscarinic Antagonists Neurotoxins Quinuclidinyl Benzilate Radioligand Assay Rats Receptors, Muscarinic Support, Non-U.S. Gov't Synaptosomes Animalia Bos taurus Bovinae Dendroaspis angusticeps Pantherophis obsoletus Serpentes Two new polypeptides were isolated and purified from the venom of the snake Dendroaspis angusticeps, which also contains other neuroactive peptides such as Dendrotoxins and Fasciculins. The amino acid composition of the peptides was determined and the first 10 amino acids from the MTX2 N-terminal fragment were sequenced. The so-called muscarinic toxins (MTX1 and MTX2) have been shown to inhibit the specific binding of [3H]QNB (0.15 nM), [3H]PZ (2.5 nM) and [3H]oxoM (2 nM) to bovine cerebral cortex membranes by 60, 88 and 82% respectively. In contrast, they caused only a 30% blockade of the [3H]QNB specific binding to similar membrane preparations from the brainstem. The Hill number for the [3H]PZ binding inhibition by the putative muscarinic toxin MTX2 was 0.95 suggesting homogeneity in the behaviour of the sites involved. The data from [3H]oxoM binding gave a Hill number of 0.83. The decreases in the specific binding involved increases in KD for the three different ligands (8-fold for [3H]QNB, 4-fold for [3H]PZ and 3,5-fold for [3H]oxoM) without significant changes in Bmax, except for a slight decrease in the [3H]oxoM binding sites (-19%); such results suggest that there may be a competitive inhibition between the MTXs and these ligands. The Ki for MTX2/[3H]PZ was 22.58 ± 3.52 nM; for MTX2/[3H]oxoM, 144.9 ± 21.07 nM and for MTX2/[3H]QNB, 134.98 ± 18.35 nM. The labelling of MTX2 with 125I allowed direct demonstration of specific and saturable binding to bovine cerebral cortex synaptosomal membranes. In conclusion, the results reported in this study strongly support the hypotheses that the two polypeptides isolated from D. angusticeps venom selectively inhibit specific ligand binding to central muscarinic receptors, in a competitive manner at least for the antagonist [3H]PZ and that the MTX2 specifically binds to a central site that is suggested to be a muscarinic receptor of the M1 subtype. © 1992. 1992 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v20_n2_p237_Jerusalinsky http://hdl.handle.net/20.500.12110/paper_01970186_v20_n2_p237_Jerusalinsky |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
muscarinic receptor polypeptide snake venom toxin amino acid composition amino acid sequence animal cell article binding site brain cortex cattle competitive inhibition ligand binding nonhuman priority journal protein isolation rat synaptic membrane Amino Acids Animal Brain Stem Cattle Cell Membrane Cerebral Cortex Chromatography, Gel Chromatography, High Pressure Liquid Chromatography, Ion Exchange Elapid Venoms Kinetics Muscarinic Antagonists Neurotoxins Quinuclidinyl Benzilate Radioligand Assay Rats Receptors, Muscarinic Support, Non-U.S. Gov't Synaptosomes Animalia Bos taurus Bovinae Dendroaspis angusticeps Pantherophis obsoletus Serpentes |
| spellingShingle |
muscarinic receptor polypeptide snake venom toxin amino acid composition amino acid sequence animal cell article binding site brain cortex cattle competitive inhibition ligand binding nonhuman priority journal protein isolation rat synaptic membrane Amino Acids Animal Brain Stem Cattle Cell Membrane Cerebral Cortex Chromatography, Gel Chromatography, High Pressure Liquid Chromatography, Ion Exchange Elapid Venoms Kinetics Muscarinic Antagonists Neurotoxins Quinuclidinyl Benzilate Radioligand Assay Rats Receptors, Muscarinic Support, Non-U.S. Gov't Synaptosomes Animalia Bos taurus Bovinae Dendroaspis angusticeps Pantherophis obsoletus Serpentes Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands |
| topic_facet |
muscarinic receptor polypeptide snake venom toxin amino acid composition amino acid sequence animal cell article binding site brain cortex cattle competitive inhibition ligand binding nonhuman priority journal protein isolation rat synaptic membrane Amino Acids Animal Brain Stem Cattle Cell Membrane Cerebral Cortex Chromatography, Gel Chromatography, High Pressure Liquid Chromatography, Ion Exchange Elapid Venoms Kinetics Muscarinic Antagonists Neurotoxins Quinuclidinyl Benzilate Radioligand Assay Rats Receptors, Muscarinic Support, Non-U.S. Gov't Synaptosomes Animalia Bos taurus Bovinae Dendroaspis angusticeps Pantherophis obsoletus Serpentes |
| description |
Two new polypeptides were isolated and purified from the venom of the snake Dendroaspis angusticeps, which also contains other neuroactive peptides such as Dendrotoxins and Fasciculins. The amino acid composition of the peptides was determined and the first 10 amino acids from the MTX2 N-terminal fragment were sequenced. The so-called muscarinic toxins (MTX1 and MTX2) have been shown to inhibit the specific binding of [3H]QNB (0.15 nM), [3H]PZ (2.5 nM) and [3H]oxoM (2 nM) to bovine cerebral cortex membranes by 60, 88 and 82% respectively. In contrast, they caused only a 30% blockade of the [3H]QNB specific binding to similar membrane preparations from the brainstem. The Hill number for the [3H]PZ binding inhibition by the putative muscarinic toxin MTX2 was 0.95 suggesting homogeneity in the behaviour of the sites involved. The data from [3H]oxoM binding gave a Hill number of 0.83. The decreases in the specific binding involved increases in KD for the three different ligands (8-fold for [3H]QNB, 4-fold for [3H]PZ and 3,5-fold for [3H]oxoM) without significant changes in Bmax, except for a slight decrease in the [3H]oxoM binding sites (-19%); such results suggest that there may be a competitive inhibition between the MTXs and these ligands. The Ki for MTX2/[3H]PZ was 22.58 ± 3.52 nM; for MTX2/[3H]oxoM, 144.9 ± 21.07 nM and for MTX2/[3H]QNB, 134.98 ± 18.35 nM. The labelling of MTX2 with 125I allowed direct demonstration of specific and saturable binding to bovine cerebral cortex synaptosomal membranes. In conclusion, the results reported in this study strongly support the hypotheses that the two polypeptides isolated from D. angusticeps venom selectively inhibit specific ligand binding to central muscarinic receptors, in a competitive manner at least for the antagonist [3H]PZ and that the MTX2 specifically binds to a central site that is suggested to be a muscarinic receptor of the M1 subtype. © 1992. |
| title |
Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands |
| title_short |
Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands |
| title_full |
Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands |
| title_fullStr |
Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands |
| title_full_unstemmed |
Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands |
| title_sort |
two polypeptides from dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands |
| publishDate |
1992 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v20_n2_p237_Jerusalinsky http://hdl.handle.net/20.500.12110/paper_01970186_v20_n2_p237_Jerusalinsky |
| _version_ |
1768545597565960192 |