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• W2108482989 abstract "Peptides related to the N-terminal region of calcitonin gene-related peptide (CGRP) were tested for their ability to modulate neuronal nicotinic acetylcholine receptors (nAChRs) of rat cultured chromaffin cells under whole cell patch-clamp conditions. Although CGRP(1-7) and CGRP(2-7) depressed responses mediated by nAChRs, CGRP(1-6), CGRP(1-5), or CGRP(1-4) rapidly and reversibly potentiated submaximal nicotine currents while sparing maximal currents. CGRP(1-3) was inactive. The threshold concentration for the enhancing effect of CGRP(1-6) was 0.1 microM. CGRP(1-5) or CGRP(1-4) were less effective than CGRP(1-6). Coapplication of CGRP(1-6) and of the allosteric potentiator physostigmine (0.5 microM) gave additive effects on nicotine currents. CGRP(1-6) did not enhance responses generated by muscle-type nicotinic receptors of cultured myoblasts or by gamma-aminobutyric acid(A) receptors expressed by human embryonic kidney cells. Molecular dynamics (MD) simulations suggested that CGRP(1-7) exhibited a relatively rigid ring structure imparted by the disulfide bridge between Cys(2) and Cys(7). The circular dichroism (CD) spectrum recorded from the same peptide was in agreement with this result. Shorter peptides, missing such a bridge, exhibited propensity for alpha-helix configuration. Replacing Cys(7) with Ala yielded CGRP(1-7A), a fragment with partial alpha-helix structure and ability to enhance nicotine currents. CD measurements on CGRP(1-6) were compatible with these MD structural findings. Short terminal fragments of CGRP represent a novel class of substances with selective, rapid, and reversible potentiation of nAChRs." @default.
• W2108482989 created "2016-06-24" @default.
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• W2108482989 date "2002-01-01" @default.
• W2108482989 modified "2023-10-03" @default.
• W2108482989 title "A Novel Class of Peptides with Facilitating Action on Neuronal Nicotinic Receptors of Rat Chromaffin Cells in Vitro: Functional and Molecular Dynamics Studies" @default.
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• W2108482989 doi "https://doi.org/10.1124/mol.61.1.43" @default.
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