Somatostatin receptors are expressed by immature cerebellar granule cells: evidence for a direct inhibitory effect of somatostatin on neuroblast activity.
Somatostatin and somatostatin receptors are transiently expressed in the immature rat cerebellar cortex but virtually undetectable in the cerebellum of adults. Although somatostatin binding sites have been visualized during the postnatal period in the external granule cell layer, the type of cell that expresses somatostatin receptors has never been identified; thus, the potential function of somatostatin in the developing cerebellum remains unknown. In the present study, we have taken advantage of the possibility of obtaining a culture preparation that is greatly enriched in immature cerebellar granule cells to investigate the presence of somatostatin receptors and the effect of somatostatin on intracellular messengers on cerebellar neuroblasts in primary culture. Autoradiographic labeling revealed the occurrence of a high density of binding sites for radioiodinated Tyr-[D-Trp8]somatostatin-(1-14) on 1-day-old cultured immature granule cells. Saturation and competition studies showed the existence of a single class of high-affinity binding sites (Kd = 0.133 +/- 0.013 nM, Bmax = 3038 +/- 217 sites per cell). Somatostatin induced a dose-dependent inhibition of forskolin-evoked cAMP formation (ED50 = 10 nM), and this effect was prevented by preincubation of cultured immature granule cells with pertussis toxin. Somatostatin also caused a marked reduction of intracellular calcium concentration. These results show the presence of functionally active somatostatin receptors on immature granule cells. Our data suggest the possible involvement of somatostatin in the regulation of proliferation and/or migration of neuroblasts during the development of the cerebellar cortex.
Gonzalez
B
B
European Institute for Peptide Research, Centre National de la Recherche Scientifique Unité Recherche Associée 650, University of Rouen, Mont-Saint-Aignan, France.
Leroux
P
P
Lamacz
M
M
Bodenant
C
C
Balazs
R
R
Vaudry
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015398:Signal Transduction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*
D017481:Receptors, Somatostatin; D005576:Colforsin; D013004:Somatostatin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium