Hippocampal sst(1) receptors are autoreceptors and do not affect seizures in rats.
Somatostatin-14 (SRIF-14) exerts anticonvulsive effects in several rat seizure models, generally attributed to sst(2) receptor activation. Whereas sst(1) immunoreactivity has been localized to both polymorphic interneurons and principal cells in the rat hippocampus, its potential role as an inhibitory autoreceptor or as a receptor involved in mediating anticonvulsive actions remains unknown. We showed that intrahippocampal administration of the sst(1) antagonist SRA880 (1 microM) induced a robust increase in hippocampal SST-14 levels without affecting gamma-aminobutyric acid levels in conscious rats, indicating that the sst(1) receptor acts as an inhibitory autoreceptor. SRA880 did not affect seizure severity and did not reverse the anticonvulsive action of SRIF-14 (1 microM) against pilocarpine-induced seizures, suggesting that hippocampal sst(1) receptors are not involved in the anticonvulsive effects of SRIF-14.
De Bundel
Dimitri
D
Department of Pharmaceutical Chemistry, Research Group Experimental Neuropharmacology, Drug Analysis and Drug Information, Vrije Universiteit Brussel, Brussels, Belgium.
Aourz
Najat
N
Kiagiadaki
Foteini
F
Clinckers
Ralph
R
Hoyer
Daniel
D
Kastellakis
Andreas
A
Michotte
Yvette
Y
Thermos
Kyriaki
K
Smolders
Ilse
I
D000818:Animals; D017660:Autoreceptors / Q000378:metabolism*; D002853:Chromatography, Liquid; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D008845:Microinjections / Q000379:methods; D018721:Muscarinic Agonists; D010862:Pilocarpine; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013004:Somatostatin / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C488795:1,2,3,4,4a,5,10,10a-octahydro-6-methoxy-1-methylbenz(g)quinoline-3-carboxylic acid 4-(4-nitrophenyl)piperazine amide; D017660:Autoreceptors; D018721:Muscarinic Agonists; D010879:Piperazines; D011804:Quinolines; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D010862:Pilocarpine; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid