DISTINCT PATTERNS OF EXPRESSION AND PHYSIOLOGICAL-EFFECTS OF SST1 ANDSST2 RECEPTOR SUBTYPES IN MOUSE HYPOTHALAMIC NEURONS AND ASTROCYTES IN CULTURE

Somatostatin (SRIF) receptor subtypes (sst) were characterized in hypo thalamic neurons and astrocytes by quantitative reverse transcription- polymerase chain reaction and radioreceptor assays using [I-125-Tyr(0) ,D-Trp(8)]SRIF-14 as a ligand in ionic conditions discriminating betwe en SRIF-1 (sst2, -3, and -5 receptors) and SRIF-2 (sst1 and -4 recepto rs) binding sites. In neurons, sst1 mRNA levels were twofold higher th an those of sst2, and sst3-5 expression was only minor. Astrocytes exp ressed 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, compl etely 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 SRI F-2 conditions, only SRIF-14 and CH-275 displaced the binding on neuro ns. No SRIF-2 binding was observed on glia. SRIF-14 and octreotide inh ibited forskolin-stimulated adenylyl cyclase activity in neurons and g lia, whereas CH-275 was effective in neurons only. In patch-clamp expe riments, SRIF-14 modulated the glutamate sensitivity of hypothalamic n eurons with either synergistic or antagonistic effects; CH-275 was onl y stimulatory and octreotide inhibitory. It is concluded that hypothal amic neurons express primarily sst1 and sst2, sst2 predominates in ast rocytes, and both receptors induce distinct biological effects.