Distinct Patterns of Expression and Physiological Effects of sst1 and sst2 Receptor Subtypes in Mouse Hypothalamic Neurons and Astrocytes in Culture

Somatostatin (SRIF) receptor subtypes (sst) were characterized in hypothalamic neurons and astrocytes by quantitative reverse transcription-polymerase chain reaction and radioreceptor assays using [ 125 I-Tyr 0 ,D-Trp 8 ]SRIF-14 as a ligand in ionic conditions discriminating between SRIF-1 (sst2, -3, and -5 receptors) and SRIF-2 (sstl 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-Trp 8 ,IAmp 9 ]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 sstl and sst2, sst2 predominates in astrocytes, and both receptors induce distinct biological effects.