PcTx1 affords neuroprotection in a conscious model of stroke in hypertensive rats via selective inhibition of ASIC1a

Neuropharmacology
Claudia A McCarthyRobert E Widdop

Abstract

Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and plays a major role in neuronal injury following cerebral ischemia. Evidence that inhibition of ASIC1a might be neuroprotective following stroke was previously obtained using "PcTx1 venom" from the tarantula Psalmopeous cambridgei. We show here that the ASIC1a-selective blocker PcTx1 is present at only 0.4% abundance in this venom, leading to uncertainty as to whether the observed neuroprotective effects were due to PcTx1 blockade of ASIC1a or inhibition of other ion channels and receptors by the hundreds of peptides and small molecules present in the venom. We therefore examined whether pure PcTx1 is neuroprotective in a conscious model of stroke via direct inhibition of ASIC1a. A focal reperfusion model of stroke was induced in conscious spontaneously hypertensive rats (SHR) by administering endothelin-1 to the middle cerebral artery via a surgically implanted cannula. Two hours later, SHR were treated with a single intracerebroventricular (i.c.v.) dose of PcTx1 (1 ng/kg), an ASIC1a-inactive mutant of PcTx1 (1 ng/kg), or saline, and ledged beam and neurological tests were used to assess the severity of symptomatic changes. PcTx1 markedly red...Continue Reading

References

Jun 1, 2000·The Journal of Biological Chemistry·P EscoubasM Lazdunski
Sep 23, 2000·Journal of Neuroscience Methods·J K CallawayP M Delaney
Sep 3, 2002·The Journal of Physiology·Nicola J Allen, David Attwell
Sep 2, 2003·Trends in Neurosciences·Oleg Krishtal
Apr 1, 2006·Toxicon : Official Journal of the International Society on Toxinology·Pierre EscoubasGlenn F King
Aug 8, 2006·Trends in Neurosciences·John A WemmieMichael J Welsh
Nov 28, 2006·Frontiers in Bioscience : a Journal and Virtual Library·Zhi-Gang XiongRoger P Simon
Sep 21, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Giuseppe PignataroRoger P Simon
Apr 4, 2008·Trends in Pharmacological Sciences·Elaine BesanconEng H Lo
Feb 28, 2009·Stroke; a Journal of Cerebral Circulation·Marc FisherUNKNOWN STAIR Group
Feb 28, 2009·Stroke; a Journal of Cerebral Circulation·Claudia A McCarthyRobert E Widdop
Mar 11, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Minghua LiZhi-Gang Xiong
Jul 31, 2010·Neuron·Michael A MoskowitzCostantino Iadecola
Nov 3, 2010·The Journal of Biological Chemistry·Erin N HoaglandCandice C Askwith
Jan 27, 2011·Molecular Neurodegeneration·Trent M WoodruffThiruma V Arumugam
Oct 2, 2012·Annual Review of Entomology·Glenn F King, Margaret C Hardy
Jan 7, 2014·Translational Stroke Research·Zaven O'BryantZhi-Gang Xiong

❮ Previous
Next ❯

Citations

Jan 31, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·V O ZambelliY Cury
Mar 14, 2016·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Shen YangYunlin Liu
Oct 14, 2017·Translational Stroke Research·Yandong RenXiang-Ping Chu
Oct 14, 2017·Molecular Pharmacology·Axel SchmidtStefan Gründer
Nov 1, 2018·Current Medicinal Chemistry·Xinwang YangEng-Ang Ling
Aug 29, 2020·Acta Pharmacologica Sinica·Zheng-Wei LuoHong-Shuo Sun
Mar 13, 2018·Frontiers in Pharmacology·Jessica M de SouzaFabiola M Ribeiro
May 10, 2018·Scientific Reports·Yi LiuJeffrey Schoellerman
Aug 1, 2020·Frontiers in Pharmacology·Dmitry I OsmakovSergey A Kozlov
Oct 17, 2018·International Journal of Molecular Sciences·Mélanie LambertFabrice Antigny
Dec 13, 2018·Neural Regeneration Research·Jamileh DibasAdnan Dibas
Mar 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Irène R ChassagnonGlenn F King
Jan 1, 2021·Biochemical and Biophysical Research Communications·Saige YinXinwang Yang
Jun 15, 2020·Biochemical Pharmacology·Volker HerzigGlenn F King
Aug 29, 2021·Biological Reviews of the Cambridge Philosophical Society·Tim LüddeckeAndreas Vilcinskas

❮ Previous
Next ❯

Related Concepts

Related Feeds

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.