Receptors and effects of the inhibitory neuropeptide somatostatin in microglial cells

The expression of receptors for the neuropeptide somatostatin was investigated in cultured immunocytochemically pure rat microglial cells. By the reverse transcriptase-polymerase chain reaction, the mRNAs for the receptor subtypes sst(2), sst(3) and sst(4), but not sst(1) and sst(5) could be detected. To show that these receptors were functionally active, the effects of somatostatin and the metabolically stable, receptor subtype (2, 3 and 5) selective derivative octreotide (SMS 201-995, Sandostatin) on protein phosphorylation and proliferation were evaluated. Somatostatin induced the tyrosine phosphorylation of a 95 kDa protein in microglia. Furthermore, somatostatin or octreotide inhibited the basal as well as the GM-CSF-(granulocyte macrophage colony-stimulating factor) or the IL-3-(interleukin-3)-stimulated proliferation of microglial cells. This effect was dose-dependent, with a half maximum activity of about 0.2-0.3 nM. Somatostatin was relatively stable in the cultures due to protease inhibitors in the serum. The results indicate that microglial cells are targets for the widespread neuropeptide somatostatin and that its receptors can transduce complex signals to microglia. (C) 1998 Elsevier Science B.V. All rights reserved.