NH(2)-terminal modification of a channel-forming peptide increases capacity for epithelial anion secretion.
NH(2)-terminal modification of a channel-forming peptide increases capacity for epithelial anion secretion.
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通道形成肽的 NH(2) 末端修饰可增加上皮阴离子分泌的能力。
DOI:
10.1152/ajpcell.2001.280.3.c451
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发表时间:
2001
期刊:
影响因子:
--
通讯作者:
Schultz,BD
中科院分区:
文献类型:
--
作者:
Broughman,JR;Mitchell,KE;Sedlacek,RL;Iwamoto,T;Tomich,JM;Schultz,BD
A synthetic, channel-forming peptide, derived from the α-subunit of the glycine receptor (M2GlyR), has been synthesized and modified by adding four lysine residues to the NH2terminus (N-K4-M2GlyR). In Ussing chamber experiments, apical N-K4-M2GlyR (250 μM) increased transepithelial short-circuit current (Isc) by 7.7 ± 1.7 and 10.6 ± 0.9 μA/cm2in Madin-Darby canine kidney and T84 cell monolayers, respectively; these values are significantly greater than those previously reported for the same peptide modified by adding the lysines at the COOH terminus (Wallace DP, Tomich JM, Iwamoto T, Henderson K, Grantham JJ, and Sullivan LP.Am J Physiol Cell Physiol272: C1672–C1679, 1997). N-K4-M2GlyR caused a concentration-dependent increase inIsc(k[1/2]= 190 μM) that was potentiated two- to threefold by 1-ethyl-2-benzimidazolinone. N-K4-M2GlyR-mediated increases inIscwere insensitive to changes in apical cation species. Pharmacological inhibitors of endogenous Cl−conductances [glibenclamide, diphenylamine-2-dicarboxylic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, 4,4′-dinitrostilben-2,2′-disulfonic acid, indanyloxyacetic acid, and niflumic acid] had little effect on N-K4-M2GlyR-mediatedIsc. Whole cell membrane patch voltage-clamp studies revealed an N-K4-M2GlyR-induced anion conductance that exhibited modest outward rectification and modest time- and voltage-dependent activation. Planar lipid bilayer studies yielded results indicating that N-K4-M2GlyR forms a 50-pS anion conductance with ak[1/2]for Cl−of 290 meq. These results indicate that N-K4-M2GlyR forms an anion-selective channel in epithelial monolayers and shows therapeutic potential for the treatment of hyposecretory disorders such as cystic fibrosis.
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DOI:
--
发表时间:
1993
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
Reddy,GL;Iwamoto,T;Tomich,JM;Montal,M
通讯作者:
Montal,M
DOI:
10.1016/s0005-2736(00)00170-x
发表时间:
2000
期刊:
Biochimica et biophysica acta
影响因子:
--
作者:
Mitchell,KE;Iwamoto,T;Tomich,J;Freeman,LC
通讯作者:
Freeman,LC
影响因子:
30.8
作者:
Rozmahel, R;Wilschanski, M;Tsui, LC
通讯作者:
Tsui, LC
影响因子:
3.4
作者:
Tomich,JM;Wallace,D;Henderson,K;Mitchell,KE;Radke,G;Brandt,R;Ambler,CA;Scott,AJ;Grantham,J;Sullivan,L;Iwamoto,T
通讯作者:
Iwamoto,T
DOI:
10.1152/ajpcell.1995.269.2.c451
发表时间:
1995
期刊:
The American journal of physiology.
影响因子:
--
作者:
Schwiebert,EM;Gruenert,DC;Guggino,WB;Stanton,BA
通讯作者:
Stanton,BA