title: Distinct patterns of expression and physiological effects of sst1 and sst2 receptor subtypes in mouse hypothalamic neurons and astrocytes in culture.
abstract: Somatostatin (SRIF) receptor subtypes (sst) were characterized in hypothalamic neurons and astrocytes by quantitative reverse transcription-polymerase chain reaction and radioreceptor assays using [125I-Tyr0,D-Trp8]SRIF-14 as a ligand in ionic conditions discriminating between SRIF-1 (sst2, -3, and -5 receptors) and SRIF-2 (sst1 and -4 receptors) binding sites. In neurons, sstl mRNA levels were twofold higher than those of sst2, and sst3-5 expression was only minor. Astrocytes expressed 10-fold less sst mRNAs than neurons, which corresponded mostly (80%) to sst2. SRIF-1 binding site radioautography indicated that 10% of hypothalamic neurons were labelled on both cell bodies and neuritic processes, as were 35% of astrocytes. On neuronal and glial membranes, SRIF-14 and octreotide, an sst2/sst3/sst5-selective analogue, completely displaced SRIF-1 binding, whereas des-AA(1,2,5)[D-Trp8,IAmp9]SRIF (CH-275), an sst1-selective analogue, was ineffective. Using SRIF-2 conditions, only SRIF-14 and CH-275 displaced the binding on neurons. No SRIF-2 binding was observed on glia. SRIF-14 and octreotide inhibited forskolin-stimulated adenylyl cyclase activity in neurons and glia, whereas CH-275 was effective in neurons only. In patch-clamp experiments, SRIF-14 modulated the glutamate sensitivity of hypothalamic neurons with either synergistic or antagonistic effects; CH-275 was only stimulatory and octreotide inhibitory. It is concluded that hypothalamic neurons express primarily sst1 and sst2, sst2 predominates in astrocytes, and both receptors induce distinct biological effects.
authors.affiliation: U.159 INSERM, Centre Paul Broca, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Viollet
authors.forename: C
authors.initials: C
authors.lastname: Lanneau
authors.forename: A
authors.initials: A
authors.lastname: Faivre-Bauman
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Djordjijevic
authors.forename: C
authors.initials: C
authors.lastname: Loudes
authors.forename: R
authors.initials: R
authors.lastname: Gardette
authors.forename: C
authors.initials: C
authors.lastname: Kordon
authors.forename: J
authors.initials: J
authors.lastname: Epelbaum
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D001345:Autoradiography; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology*; D007457:Iodine Radioisotopes; D051379:Mice; D009474:Neurons / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D015282:Octreotide / Q000378:metabolism / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D006728:Hormones; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D005576:Colforsin; D018698:Glutamic Acid; D013004:Somatostatin; D000262:Adenylyl Cyclases; D015282:Octreotide