Document Detail

Senktide-induced gerbil foot tapping behaviour is blocked by selective tachykinin NK1 and NK3 receptor antagonists.
MedLine Citation:
PMID:  17920583     Owner:  NLM     Status:  MEDLINE    
Intracerebroventricular (i.c.v.) administration of tachykinin NK(1) receptor agonists induces tapping of the hind legs in gerbils, so-called gerbil foot tapping, which is thought to reflect a fear-related response. The aim of the present study was to examine how ligands selective for NK(1), NK(2) and NK(3) receptors affect the gerbil foot tap response. Agonists selective for NK receptor subtypes were administered i.c.v. and the gerbil foot tap response was monitored. The effect of systemically administered antagonists was also studied. The interaction of ligands with gerbil NK(1) receptors was evaluated using autoradiography on gerbil brain slices with [(3)H]-Sar,Met(O(2))-substance P or [(3)H]GR205171 as radioligand. The effects of ligands on NK(1) and NK(3) receptor-mediated increases in intracellular calcium in vitro were studied in Chinese hamster ovary cells expressing the cloned gerbil receptors. The selective NK(1) receptor agonist ASMSP and the selective NK(3) receptor agonist senktide induced dose-dependent increases in gerbil foot tapping with similar potency. The maximal effect of senktide was approximately 40% of the maximal response evoked by ASMSP. The effects of ASMSP and senktide were blocked by administration of the selective NK(1) receptor antagonist CP99,994 (10 micromol/kg s.c.). The effects of senktide, but not ASMSP, were blocked by administration of the selective NK(3) receptor antagonist SB223412 (50 micromol/kg i.p.). Senktide did not displace NK(1) receptor radioligand binding and was >1000-fold less potent than ASMSP at activating gerbil NK(1) receptors. The selective NK(3) receptor agonist senktide evokes fear-related gerbil foot tapping, an effect which probably involves indirect enhancement of NK(1) receptor signalling.
Monika Sundqvist; Elin Kristensson; Rebecka Adolfsson; Agnes Leffler; Ingela Ahlstedt; Susanna Engberg; Tomas Drmota; Kalle Sigfridsson; Rainer Jussila; Jennie de Verdier; Anna Novén; Anders Johansson; Ingrid Påhlman; Bengt von Mentzer; Erik Lindström
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Publication Detail:
Type:  Journal Article     Date:  2007-09-11
Journal Detail:
Title:  European journal of pharmacology     Volume:  577     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-10-30     Completed Date:  2008-02-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  78-86     Citation Subset:  IM    
AstraZeneca R&D, Mölndal, Sweden.
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MeSH Terms
Behavior, Animal / drug effects*
Brain / metabolism
CHO Cells
Calcium / metabolism
Cloning, Molecular
Dose-Response Relationship, Drug
Injections, Intraventricular
Neurokinin A / analogs & derivatives,  pharmacology
Peptide Fragments / antagonists & inhibitors*,  pharmacology*
Piperidines / pharmacology
Quinolines / pharmacology
Receptors, Neurokinin-1 / antagonists & inhibitors*
Receptors, Neurokinin-2 / antagonists & inhibitors
Receptors, Neurokinin-3 / antagonists & inhibitors*
Substance P / analogs & derivatives*,  antagonists & inhibitors,  pharmacology
Reg. No./Substance:
0/Peptide Fragments; 0/Piperidines; 0/Quinolines; 0/Receptors, Neurokinin-1; 0/Receptors, Neurokinin-2; 0/Receptors, Neurokinin-3; 0/substance P(4-11), beta Ala(4)-Ser(9)-Met(O2)(11)-; 106128-89-6/senktide; 133156-06-6/GR 73632; 136548-07-7/neurokinin A (3-10), lysyl(3)-glycyl(8)-R-lactam-leucine(9)-; 136982-36-0/3-(2-methoxybenzylamino)-2-phenylpiperidine; 174636-32-9/SB 223412; 33507-63-0/Substance P; 7440-70-2/Calcium; 86933-74-6/Neurokinin A

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