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.

Calcium channel activation stabilizes a neuronal calcium channel mRNA

“…Our studies highlight a different calcium-signaling pathway that couples depolarization to increased levels of a calcium-channel mRNA by slowing the rate of its degradation 29,30 . The inhibitory effects of nimodipine (Fig.…”

“…Calcium can also inhibit the degradation of certain mRNAs 29,30 . We therefore tested if L channels mediated the effect of potassium-induced depolarization on the long form of α 1B mRNA.…”

Modulation of somatostatin receptors, somatostatin content and Gi proteins by substance P in the rat frontoparietal cortex and hippocampus

“…Thus, an increase in cAMP formation by SP‐mediated NK 1 receptor activation could enhance SRIF gene transcription, which would explain the increase in cortical and hippocampal SRIF‐LI content induced by SP treatment in our study. In addition, Ca 2+ can also induce SRIF gene transcription via Ca 2+ ‐dependent PKI and PKII‐mediated phosphorylation of CREB (Tolon et al . 1994).…”

Biology of Somatostatin and Somatostatin Receptors in Breast Cancer

“…In addition, tissue-specific promoter elements consisting of TAAT motifs that operate in concert with CRE to provide high-level constitutive activity are reiterated three times over a 500-nucleotide region (150). Many of the agents that influence SST secretion are also capable of altering SST gene expression ( (1,131,153,205). cAMP is a potent activator of both gene transcription and secretion of SST and has emerged as the most prominent signaling pathway for regulating SST function.…”