WIN 17317-3 : novel nonpeptide antagonist of voltage-activated K+ channels in human T lymphocytes
We report the in vitro biological characterization of WIN 17317-3 (1-benzyl-7-chloro-4-n-propylimino-1,4-dihydroquinoline hydrochloride), a novel inhibitor of voltage-activated (n-type) K+ channels in human T lymphocytes. WIN 17317-3 inhibits 125I-charybdotoxin binding to n-type K+ channels with an IC50 value of 83 +/- 4 nM. WIN 17317-3 demonstrates competitive inhibition of 125I-charybdotoxin binding by increasing its dissociation constant without changing the total number of channels bound and by having no effect on its dissociation rate constant. WIN 17317-3 inhibits whole-cell, n-type K+ currents with characteristics indicative of open channel block and has an IC50 value of 335 nM. The compound is 150-fold selective for n-type K+ channels, compared with Ca(2+)-activated, charybdotoxin-sensitive K+ channels in smooth muscle. In purified CD4+ T lymphocytes activated with either anti-CD3 plus phorbol ester or anti-CD3 plus anti-CD28, WIN 17317-3 decreases interleukin-2 production with EC50 values of 0.8 microM and 1 microM, respectively. WIN 17317-3 is a novel, potent, and selective nonpeptide n-type K+ channel antagonist that inhibits interleukin-2 production in human T lymphocytes.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1995 |
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| Erschienen: |
1995 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:48 |
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| Enthalten in: |
Molecular pharmacology - 48(1995), 1 vom: 23. Juli, Seite 98-104 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hill, R J [VerfasserIn] |
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| Themen: |
115422-61-2 |
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| Anmerkungen: |
Date Completed 30.08.1995 Date Revised 17.11.2004 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM075189151 |
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| 100 | 1 | |a Hill, R J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a WIN 17317-3 |b novel nonpeptide antagonist of voltage-activated K+ channels in human T lymphocytes |
| 264 | 1 | |c 1995 | |
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| 500 | |a Date Completed 30.08.1995 | ||
| 500 | |a Date Revised 17.11.2004 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We report the in vitro biological characterization of WIN 17317-3 (1-benzyl-7-chloro-4-n-propylimino-1,4-dihydroquinoline hydrochloride), a novel inhibitor of voltage-activated (n-type) K+ channels in human T lymphocytes. WIN 17317-3 inhibits 125I-charybdotoxin binding to n-type K+ channels with an IC50 value of 83 +/- 4 nM. WIN 17317-3 demonstrates competitive inhibition of 125I-charybdotoxin binding by increasing its dissociation constant without changing the total number of channels bound and by having no effect on its dissociation rate constant. WIN 17317-3 inhibits whole-cell, n-type K+ currents with characteristics indicative of open channel block and has an IC50 value of 335 nM. The compound is 150-fold selective for n-type K+ channels, compared with Ca(2+)-activated, charybdotoxin-sensitive K+ channels in smooth muscle. In purified CD4+ T lymphocytes activated with either anti-CD3 plus phorbol ester or anti-CD3 plus anti-CD28, WIN 17317-3 decreases interleukin-2 production with EC50 values of 0.8 microM and 1 microM, respectively. WIN 17317-3 is a novel, potent, and selective nonpeptide n-type K+ channel antagonist that inhibits interleukin-2 production in human T lymphocytes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Interleukin-2 |2 NLM | |
| 650 | 7 | |a Iodine Radioisotopes |2 NLM | |
| 650 | 7 | |a Potassium Channel Blockers |2 NLM | |
| 650 | 7 | |a Potassium Channels |2 NLM | |
| 650 | 7 | |a Quinolines |2 NLM | |
| 650 | 7 | |a Scorpion Venoms |2 NLM | |
| 650 | 7 | |a WIN 17317-3 |2 NLM | |
| 650 | 7 | |a Charybdotoxin |2 NLM | |
| 650 | 7 | |a 115422-61-2 |2 NLM | |
| 700 | 1 | |a Grant, A M |e verfasserin |4 aut | |
| 700 | 1 | |a Volberg, W |e verfasserin |4 aut | |
| 700 | 1 | |a Rapp, L |e verfasserin |4 aut | |
| 700 | 1 | |a Faltynek, C |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, D |e verfasserin |4 aut | |
| 700 | 1 | |a Pagani, K |e verfasserin |4 aut | |
| 700 | 1 | |a Baizman, E |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, S |e verfasserin |4 aut | |
| 700 | 1 | |a Guiles, J W |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular pharmacology |d 1965 |g 48(1995), 1 vom: 23. Juli, Seite 98-104 |w (DE-627)NLM000021156 |x 1521-0111 |7 nnns |
| 773 | 1 | 8 | |g volume:48 |g year:1995 |g number:1 |g day:23 |g month:07 |g pages:98-104 |
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