Identification of somatostatin sst2(a) receptor expressing neurones in central regions involved in nociception.
Somatostatin is a neuromodulator and neurotransmitter in the central nervous system. Administration of somatostatin to the spinal cord or brain areas involved in nociception has been shown to result in analgesia. Little information is available about the somatostatin receptor types which may be involved in mediating the neuromodulatory and analgesic effects of the peptide. To define the neuronal systems expressing the sst2(a) receptor in brain areas associated with analgesia, immunohistochemical co-localisation studies were carried out in the periaqueductal grey (PAG) and spinal cord using an antibody specific for the sst2(a) receptor. To further define sst2(a) receptor expressing neurones, sst2(a) receptor immunohistochemistry was combined with retrograde tracing using fluorogold. In the PAG, sst2(a) receptor expressing neurones were found to co-express calbindin D28k (36%), the glutamate transporter EAAC-1 (25%), and GABA transporter GAT-1 ( approximately 10%). A total of 65% of sst2(a) positive neurones projected to the thalamus. In the spinal cord, the sst2(a) receptor shows cellular co-localisation with EAAC-1 and GAT-1. Immunohistochemistry and receptor autoradiography using [125I]BIM 23027 after dorsal rhizotomy of the lumbar dorsal roots, L4 and L5, suggests that the somatostatin sst2(a) receptor is not present on primary afferent neurones. Dorsal hemisections of the mid thoracic cord did not alter the immunohistochemical signal for the somatostatin sst2(a) receptor, providing further evidence for an intrinsic localisation of the receptor protein in the dorsal horn of the spinal cord. These data show that the somatostatin sst2(a) receptor exists on morphologically and neurochemically heterogenous neurones and is closely associated with brain areas involved in analgesia and the modulation of nociception.
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK. mys37162@ggr.co.uk
M
M
Schindler
S
S
Holloway
G
G
Hathway
C J
CJ
Woolf
P P
PP
Humphrey
P C
PC
Emson
D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009619:Nociceptors / Q000502:physiology*; D010487:Periaqueductal Gray / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013266:Stilbamidines; D014018:Tissue Distribution
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D017481:Receptors, Somatostatin; D013266:Stilbamidines; C106140:somatostatin receptor sst2A