Evidence that somatostatin sst2 receptors mediate striatal dopamine release.
1 Somatostatin (SRIF) is a cyclic tetradecapeptide present in medium-sized aspiny interneurones in the rat striatum. We have previously shown that exogenous SRIF potently stimulates striatal dopamine (DA) release via a glutamate-dependent mechanism. We now report the ability of the selective sst2 receptor agonist, BIM-23027, to mimic this effect of SRIF. 2 In vivo microdialysis studies were performed in anaesthetized male Wistar rats. In most experiments, compounds were administered by retrodialysis into the striatum for 15 min periods, 90 min and 225 min after sampling commenced, with levels of neurotransmitters being measured by HPLC with electrochemical and fluorescence detection. 3 BIM-23027 (50 and 100 nM) stimulated DA release with extracellular levels increasing by up to 18 fold. 4 Prior retrodialysis of BIM-23027 (50 nM) abolished the effects of subsequent administration of SRIF (100 nM). 5 The agonist effects of both BIM-23027 and SRIF were abolished by the selective sst2 receptor antagonist, L-Tyr8-CYN-154806 (100 nM). 6 The AMPA/kainate receptor antagonist, DNQX (100 microM), abolished the agonist effects of BIM-23027 as previously shown for SRIF. 7 This study provides evidence that the sst2 receptor mediates the potent dopamine-releasing actions observed with SRIF in the rat striatum. Dopamine release evoked by both peptides appears to be mediated indirectly via a glutamatergic pathway. Other subtype-specific somatostatin receptor ligands were unable to elicit any effects and therefore we conclude that no other somatostatin receptor types are involved in mediating the dopamine-releasing actions of SRIF in the striatum.
Hathway
G J
GJ
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB1 1QJ.
Humphrey
P P
PP
Kendrick
K M
KM
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000819:agonists / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000631:Aminopyridines; C091738:BIM 23027; C091737:BIM 23056; C403089:CYN 154806; D018691:Excitatory Amino Acid Antagonists; C091739:L 362855; C115929:NNC 26-9100; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011810:Quinoxalines; D017481:Receptors, Somatostatin; D013004:Somatostatin; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; D013890:Thiourea; D004298:Dopamine