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 sst2, sst3 and sst4, but not sst1 and sst5 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.
Anatomisches Institut der Universität Kiel, Olshausenstrasse 40, D-24098, Kiel, Germany.
J
J
Feindt
A
A
Schmidt
R
R
Mentlein
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015282:Octreotide / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000494:pharmacology / Q000502:physiology*; D014158:Transcription, Genetic
D007377:Interleukin-3; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015282:Octreotide