Somatostatin stimulates striatal acetylcholine release by glutamatergic receptors: an in vivo microdialysis study.
The modulation of striatal cholinergic neurons by somatostatin (SOM) was studied by measuring the release of acetylcholine (ACh) in the striatum of freely moving rats. The samples were collected via a transversal microdialysis probe. ACh level in the dialysate was measured by the high performance liquid chromatography method with an electrochemical detector. Local administration of SOM (0.1, 0.5 and 1 microM) produced a long-lasting and concentration-dependent increase in the basal striatal ACh output. The stimulant effect of SOM was antagonized by the SOM receptor antagonist cyclo(7-aminopentanoyl-Phe-D-Trp-Lys-Thr[BZL]) (1 microM). In a series of experiments, we studied the effect of 6,7-dinitroquinoxaline-2, 3-dione (DNQX), a selective non-NMDA (N-methyl-D-aspartate) glutamatergic antagonist, on the basal and SOM-induced ACh release from the striatum. DNQX, 2 microM, perfused through the striatum had no effect on the basal ACh output but inhibited the SOM (1 microM)-induced ACh release. The non-NMDA glutamatergic receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3- benzodiazepine (GYKI-52466), 10 microM, antagonized the SOM (1 microM)-induced release of ACh in the striatum. Local administration of the NMDA glutamatergic receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV), 100 microM, blocked SOM (1 microM)-evoked ACh release. Local infusion of tetrodotoxin (1 microM) decreased the basal release of ACh and abolished the 1 microM SOM-induced increase in ACh output suggesting that the stimulated release of ACh depends on neuronal firing. The present results are the first to demonstrate a neuromodulatory role of SOM in the regulation of cholinergic neuronal activity of the striatum of freely moving rats. The potentiating effect of SOM on ACh release in the striatum is mediated (i) by SOM receptor located on glutamatergic nerve terminals, and (ii) by NMDA and non-NMDA glutamatergic receptors located on dendrites of cholinergic interneurones of the striatum.
Rakovska
Angelina
A
Laboratory Neuropeptides, Institute of Physiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, bl. 23, 1113, Sofia, Bulgaria. rakovska@bio25.bas.bg
Kiss
Janos P
JP
Raichev
Peter
P
Lazarova
Maria
M
Kalfin
Reni
R
Milenov
Kiril
K
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; C036876:cyclo(7-aminoheptanoyl-phenylalanyl-tryptophyl-lysyl-threonyl); C061950:GYKI 52466; D001569:Benzodiazepines; D013779:Tetrodotoxin; D013004:Somatostatin; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; D000109:Acetylcholine