title: Effect of potassium-induced depolarization on somatostatin gene expression in cultured fetal rat cerebrocortical cells.
abstract: The stimulatory effect of potassium depolarization upon somatostatin (SS) mRNA levels in primary cultures of fetal cerebrocortical cells was analyzed. Depolarizing stimuli, such as 56 mM K+ exposure for 30 min, elicited an increase in immunoreactive somatostatin (IR-SS) release to the media and decreased SS mRNA levels. These were increased when exposure to depolarization stimuli was prolonged up to 3 or more hr. At this time, potassium (30 and 56 mM) acted as a secretagogue, stimulating SS secretion, but was also effective in stimulating SS mRNA levels, suggesting that SS secretion can be coupled to SS mRNA accumulation. These changes were inhibited by the Ca2+ channel antagonist verapamil. In contrast, Na+ channel blockade by TTX did not modify the 24 hr potassium-induced increase in SS mRNA, although it partially abolished potassium-induced SS secretion. Examination of the rate of disappearance of SS mRNA levels after inhibition of mRNA transcription by actinomycin-D revealed that K+ stimulation of cerebrocortical cells stabilized the SS mRNA. These results suggest that the induction of SS mRNA expression by K+ is dose dependent, and involves the modulation of ion channels. The time-course study confirmed that the K(+)-induced SS mRNA accumulation is time dependent, chronic activation of the Ca2+ channels being necessary to stimulate SS gene expression. K+ stimulation may also increase the level of SS mRNA in cerebrocortical cells by reducing its rate of degradation.
authors.affiliation: Servicio de Endocrinología, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: R M
authors.initials: RM
authors.lastname: Tolón
authors.forename: F
authors.initials: F
authors.lastname: Sánchez Franco
authors.forename: M T
authors.initials: MT
authors.lastname: de los Frailes
authors.forename: M J
authors.initials: MJ
authors.lastname: Lorenzo
authors.forename: L
authors.initials: L
authors.lastname: Cacicedo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D005333:Fetus / Q000502:physiology; D015870:Gene Expression; D011188:Potassium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013004:Somatostatin / Q000235:genetics*; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D013779:Tetrodotoxin; D013004:Somatostatin; D014700:Verapamil; D011188:Potassium