Endothelin-1 activates phospholipases and channels at similar concentrations in porcine coronary arteries
Sensitivity of endothelin-1 (ET-1)-ion channel interactions has been proposed to exceed that of ET-1-phospholipase activation in vascular smooth muscle. We wanted to determine whether short-circuiting ion channels with staphylococcal alpha-toxin pores would shift the ET-1-force relation to the right as predicted from the above proposal. Medium size porcine coronary arteries (outer diameter 0.7-1.5 mm) were mounted on isometric force transducers. ET-1 concentration response curves were compared between intact rings and those subjected to alpha-toxin treatment with Ca buffered at 0.1 microM. The EC50 for treated rings (1.5 +/- 1.0 nM, n = 5 pigs) was similar to that for intact rings (1.9 +/- 0.4 nM). The Ca sensitivity of the alpha-toxin-treated rings (EC50 = 0.43 +/- 0.08 microM) was similar to that reported by other laboratories for intact and alpha-toxin-treated arteries and was shifted eightfold to the left by a high concentration of ET-1 (10 nM). Measurements of [32P]phosphatidic acid ([32P]PA) levels were used to evaluate phospholipase activity in intact arteries. The time courses for [32P]PA production and contraction were similar in response to high (100 nM) and to low (1 nM) ET-1. Significant increases in both steady-state contraction and [32P]PA occurred over a wide range of ET-1 concentrations tested (0.3-100 nM). Our findings support the concept that ET-1-phospholipase coupling is operative over the whole concentration range that induces contractile responses. It is suggested that both Ca entry and Ca sensitization processes are activated by ET-1 at low concentrations (<EC50) and that both processes contribute significantly to the integrated response.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
1998 |
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| Erschienen: |
1998 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:274 |
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| Enthalten in: |
The American journal of physiology - 274(1998), 6 vom: 15. Juni, Seite C1583-91 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jones, A W [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.08.1998 Date Revised 02.04.2019 published: Print Citation Status MEDLINE |
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| doi: |
10.1152/ajpcell.1998.274.6.C1583 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM09551497X |
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| 245 | 1 | 0 | |a Endothelin-1 activates phospholipases and channels at similar concentrations in porcine coronary arteries |
| 264 | 1 | |c 1998 | |
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| 500 | |a Date Completed 06.08.1998 | ||
| 500 | |a Date Revised 02.04.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Sensitivity of endothelin-1 (ET-1)-ion channel interactions has been proposed to exceed that of ET-1-phospholipase activation in vascular smooth muscle. We wanted to determine whether short-circuiting ion channels with staphylococcal alpha-toxin pores would shift the ET-1-force relation to the right as predicted from the above proposal. Medium size porcine coronary arteries (outer diameter 0.7-1.5 mm) were mounted on isometric force transducers. ET-1 concentration response curves were compared between intact rings and those subjected to alpha-toxin treatment with Ca buffered at 0.1 microM. The EC50 for treated rings (1.5 +/- 1.0 nM, n = 5 pigs) was similar to that for intact rings (1.9 +/- 0.4 nM). The Ca sensitivity of the alpha-toxin-treated rings (EC50 = 0.43 +/- 0.08 microM) was similar to that reported by other laboratories for intact and alpha-toxin-treated arteries and was shifted eightfold to the left by a high concentration of ET-1 (10 nM). Measurements of [32P]phosphatidic acid ([32P]PA) levels were used to evaluate phospholipase activity in intact arteries. The time courses for [32P]PA production and contraction were similar in response to high (100 nM) and to low (1 nM) ET-1. Significant increases in both steady-state contraction and [32P]PA occurred over a wide range of ET-1 concentrations tested (0.3-100 nM). Our findings support the concept that ET-1-phospholipase coupling is operative over the whole concentration range that induces contractile responses. It is suggested that both Ca entry and Ca sensitization processes are activated by ET-1 at low concentrations (<EC50) and that both processes contribute significantly to the integrated response | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Endothelin-1 |2 NLM | |
| 650 | 7 | |a Ion Channels |2 NLM | |
| 650 | 7 | |a Phosphatidic Acids |2 NLM | |
| 650 | 7 | |a Phospholipases |2 NLM | |
| 650 | 7 | |a EC 3.1.- |2 NLM | |
| 650 | 7 | |a Type C Phospholipases |2 NLM | |
| 650 | 7 | |a EC 3.1.4.- |2 NLM | |
| 650 | 7 | |a Calcium |2 NLM | |
| 650 | 7 | |a SY7Q814VUP |2 NLM | |
| 700 | 1 | |a Magliola, L |e verfasserin |4 aut | |
| 700 | 1 | |a Waters, C B |e verfasserin |4 aut | |
| 700 | 1 | |a Rubin, L J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The American journal of physiology |d 1945 |g 274(1998), 6 vom: 15. Juni, Seite C1583-91 |w (DE-627)NLM000012386 |x 0002-9513 |7 nnns |
| 773 | 1 | 8 | |g volume:274 |g year:1998 |g number:6 |g day:15 |g month:06 |g pages:C1583-91 |
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