Receptor-mediated internalization of somatostatin in rat cortical and hippocampal neurons.
Binding of neuropeptides to their receptors usually results in internalization of receptor-ligand complexes. This process serves a crucial role in receptor downregulation, resensitization, and transmembrane signaling. It has mainly been investigated in cells ectopically expressing recombinant receptors. In the present study, we investigated whether rat central neurons and astrocytes naturally expressing somatostatin (SRIF) receptors internalized this neuropeptide. We demonstrated that 29% of cortical and 45% of hippocampal neurons in culture expressed the SRIF receptor sst(2A) and that 40-50% of the neurons internalized fluorescent SRIF. Similarly, an important proportion of astrocytes expressed sst(2A) (up to 60% in cortical cultures) and internalized fluo-SRIF. Competition experiments using the sst(2)/sst(5)-preferring agonist SMS 201-995 (octreotide) showed that a subpopulation of neurons internalized fluo-SRIF via sst(2) and/or sst(5) receptors, but that others also did so via other subtypes. Fluo-SRIF labeling was barely competed for by the sst(1)-selective agonist CH-275, indicating that sst(1) was unlikely to be mediating SRIF internalization in hippocampal and cortical neurons. Given the paucity of sst(5) receptors in cerebral cortex and hippocampus and the poor yield of sst(4) internalization in transfected cells, we conclude that sst(2) and sst(3) subtypes are the most likely to be responsible for SRIF internalization in our culture systems.
Stroh
T
T
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Jackson
A C
AC
Dal Farra
C
C
Schonbrunn
A
A
Vincent
J P
JP
Beaudet
A
A
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D019556:COS Cells / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*
D017481:Receptors, Somatostatin; C106140:somatostatin receptor sst2A; D013004:Somatostatin