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Abstract:

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.

Registro:

Documento: Artículo
Título:Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands
Autor:Jerusalinsky, D.; Cerveñansky, C.; Peña, C.; Raskovsky, S.; Dajas, F.
Filiación:Instituto de Biologia Celular, Instituto de Física y Química Biológicas, Facultad de Medicina, Paraguay 2155, 1121 Buenos Aires, Argentina
Instituto de Investigaciones Biológicas Clemente Estable, Av. Italia 3318, 11600 Montevideo, Uruguay
Palabras clave: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
Año:1992
Volumen:20
Número:2
Página de inicio:237
Página de fin:246
DOI: http://dx.doi.org/10.1016/0197-0186(92)90173-O
Título revista:Neurochemistry International
Título revista abreviado:Neurochem. Int.
ISSN:01970186
CODEN:NEUID
CAS:Amino Acids; Elapid Venoms; Muscarinic Antagonists; Neurotoxins; Quinuclidinyl Benzilate, 6581-06-2; Receptors, Muscarinic
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01970186_v20_n2_p237_Jerusalinsky

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Citas:

---------- APA ----------
Jerusalinsky, D., Cerveñansky, C., Peña, C., Raskovsky, S. & Dajas, F. (1992) . Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands. Neurochemistry International, 20(2), 237-246.
http://dx.doi.org/10.1016/0197-0186(92)90173-O
---------- CHICAGO ----------
Jerusalinsky, D., Cerveñansky, C., Peña, C., Raskovsky, S., Dajas, F. "Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands" . Neurochemistry International 20, no. 2 (1992) : 237-246.
http://dx.doi.org/10.1016/0197-0186(92)90173-O
---------- MLA ----------
Jerusalinsky, D., Cerveñansky, C., Peña, C., Raskovsky, S., Dajas, F. "Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands" . Neurochemistry International, vol. 20, no. 2, 1992, pp. 237-246.
http://dx.doi.org/10.1016/0197-0186(92)90173-O
---------- VANCOUVER ----------
Jerusalinsky, D., Cerveñansky, C., Peña, C., Raskovsky, S., Dajas, F. Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands. Neurochem. Int. 1992;20(2):237-246.
http://dx.doi.org/10.1016/0197-0186(92)90173-O