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Human endothelin subtype a receptor enhancement during tissue culture via de novo transcription

Hansen-Schwartz, Jacob LU ; Nordström, Carl-Henrik LU and Edvinsson, Lars LU (2002) In Neurosurgery 50(1). p.127-133
Abstract
OBJECTIVE: Endothelin (ET) has, since its discovery, increasingly been considered a key player in the pathophysiological processes of cerebral vasospasm in the course of subarachnoid hemorrhage, although it remains unclear how ET is involved. We present data that indicate an inherent capacity of human cerebral arteries to change their sensitivity to ET. METHODS: Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into segments and subjected to organ culture for 48 hours. The vessels were then examined by using in vitro pharmacological methods and molecular biological techniques. RESULTS: After organ culture of the cerebral arteries, both the sensitivity to and potency of ET... (More)
OBJECTIVE: Endothelin (ET) has, since its discovery, increasingly been considered a key player in the pathophysiological processes of cerebral vasospasm in the course of subarachnoid hemorrhage, although it remains unclear how ET is involved. We present data that indicate an inherent capacity of human cerebral arteries to change their sensitivity to ET. METHODS: Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into segments and subjected to organ culture for 48 hours. The vessels were then examined by using in vitro pharmacological methods and molecular biological techniques. RESULTS: After organ culture of the cerebral arteries, both the sensitivity to and potency of ET were enhanced (maximal response, 152 +/- 9%; -log (50% effective concentration), 10.3 +/- 0.3), in comparison with data for fresh cerebral arteries. Contractions were inhibited by both FR139317 (a specific ETA receptor antagonist) and bosentan (a mixed ETA and ETB receptor antagonist), in a manner indicating the sole presence of contractile ETA receptors. An inconsistent dilative response to the selective ETB receptor agonist sarafotoxin 6c was observed; the response was preserved in some segments and abolished in others, and potentiation of the precontraction was observed in yet other segments. No isolated contractile response to sarafotoxin 6c was observed, however. In reverse transcription-polymerase chain reaction assays, both ETA and ETB receptor messenger ribonucleic acid was detected. CONCLUSION: These results demonstrate that human cerebral arteries are capable of enhancing the function of ETA receptors. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pharmacology, polymerase chain reaction, organ culture, vasospasm, intracranial, endothelins, cerebral arteries, endothelin receptors
in
Neurosurgery
volume
50
issue
1
pages
127 - 133
publisher
Congress of Neurological Surgeons
external identifiers
  • wos:000172946900030
  • pmid:11844243
ISSN
0148-396X
language
English
LU publication?
yes
id
4bd68d09-159f-41a1-a9e3-d7eca0e5207a (old id 346354)
alternative location
http://www.neurosurgery-online.com/pt/re/neurosurg/abstract.00006123-200201000-00021.htm
date added to LUP
2007-08-23 12:12:54
date last changed
2016-04-16 03:39:16
@article{4bd68d09-159f-41a1-a9e3-d7eca0e5207a,
  abstract     = {OBJECTIVE: Endothelin (ET) has, since its discovery, increasingly been considered a key player in the pathophysiological processes of cerebral vasospasm in the course of subarachnoid hemorrhage, although it remains unclear how ET is involved. We present data that indicate an inherent capacity of human cerebral arteries to change their sensitivity to ET. METHODS: Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into segments and subjected to organ culture for 48 hours. The vessels were then examined by using in vitro pharmacological methods and molecular biological techniques. RESULTS: After organ culture of the cerebral arteries, both the sensitivity to and potency of ET were enhanced (maximal response, 152 +/- 9%; -log (50% effective concentration), 10.3 +/- 0.3), in comparison with data for fresh cerebral arteries. Contractions were inhibited by both FR139317 (a specific ETA receptor antagonist) and bosentan (a mixed ETA and ETB receptor antagonist), in a manner indicating the sole presence of contractile ETA receptors. An inconsistent dilative response to the selective ETB receptor agonist sarafotoxin 6c was observed; the response was preserved in some segments and abolished in others, and potentiation of the precontraction was observed in yet other segments. No isolated contractile response to sarafotoxin 6c was observed, however. In reverse transcription-polymerase chain reaction assays, both ETA and ETB receptor messenger ribonucleic acid was detected. CONCLUSION: These results demonstrate that human cerebral arteries are capable of enhancing the function of ETA receptors.},
  author       = {Hansen-Schwartz, Jacob and Nordström, Carl-Henrik and Edvinsson, Lars},
  issn         = {0148-396X},
  keyword      = {pharmacology,polymerase chain reaction,organ culture,vasospasm,intracranial,endothelins,cerebral arteries,endothelin receptors},
  language     = {eng},
  number       = {1},
  pages        = {127--133},
  publisher    = {Congress of Neurological Surgeons},
  series       = {Neurosurgery},
  title        = {Human endothelin subtype a receptor enhancement during tissue culture via de novo transcription},
  volume       = {50},
  year         = {2002},
}