REGULATION OF SOMATOSTATIN GENE-EXPRESSION BY VERATRIDINE-INDUCED DEPOLARIZATION IN CULTURED FETAL CEREBROCORTICAL CELLS

The stimulatory effect of veratridine (VTD) depolarization upon somato statin mRNA (SS mRNA) levels in primary cultures of fetal cerebrocorti cal cells was analyzed. Depolarizing stimuli, such as 100 mu M VTD exp osure for 30 min, elicited an increase in immunoreactive somatostatin (IR-SS) release to the media without affecting SS mRNA levels. These l evels increased when exposure to depolarization stimuli was prolonged up to 3 or more hours. At this time, veratridine acted as a secretagog ue, stimulating somatostatin secretion, but was also effective in stim ulating somatostatin mRNA levels. These changes were blunted by the Na + channel blockade tetrodotoxin (TTX), and partially abolished by the Ca2+ channel antagonist, verapamil (VPM). To study whether VTD may aff ect mRNA stability we determine the rate of disappearance of SS mRNA a fter inhibition of transcription by actinomycin D and demonstrated tha t VTD stimulation did not stabilize the SS mRNA. These results indicat e that the induction of SS mRNA expression by VTD involves the modulat ion of Ca2+ and Na+ channels. The time course study confirmed that the VTD-induced SS mRNA accumulation is time-dependent, and requires a pr olonged exposure to stimulate SS gene expression. VTD stimulation does not modify the SS mRNA rate of degradation.