Rainbow trout somatostatin receptor subtypes SSTR1A, SSTR1B, and SSTR2 differentially activate the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling pathways in transfected cells

Abstract

Previously, we reported that extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), a downstream target of phosphatidylinositol 3-kinase (PI3K), mediated somatostatin (SS) inhibition of GH receptor, IGF1, and IGF1 receptor expression. In this study, we used Chinese hamster ovary-K1 cells that stably transfected individually with trout SS receptors (SSTR1A, SSTR1B, and SSTR2) to elucidate receptor-effector pathway linkages. SS induced ERK and Akt activation in a time-and concentration-related manner in all SSTR-expressing cells; however, the PI3K/Akt pathway was activated to a greater extent through SSTR1A than through either SSTR1B or SSTR2, whereas the ERK pathway was activated to a greater extent though SSTR2 than through either SSTR1A or SSTR1B. Although the ERK pathway inhibitor U0126 had no effect on Akt activation, the PI3K inhibitor LY294002 reduced ERK activation to near control levels in all SSTR-expressing cell lines, suggesting some cross talk between the pathways, possibly at the level of c-Raf, the phosphorylation of which also was induced by SS via each SSTR. Pertussis toxin (PTX) completely abolished SS-induced activation of ERK and Akt in SSTR1A-, SSTR1B-, and SSTR2-expressing cells, suggesting that these receptors link to the ERK and PI3K/Akt pathways via PTX-sensitive G-proteins. SS-induced activation of Elk1, Stat3, and C/EBPb also was mediated by each of the trout SSTRs. These findings establish important receptor-effector pathway linkages for fish SSTRs and provide insight into the molecular mechanisms by which SSs may elicit diverse physiological effects in target cells.

The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements

“…In the rainbow trout, Oncorhynchus mykiss , three sequences have been reported [42,43]. In our additional analysis the two sequences identified as SSTR1a and -1b [43,44] can be correctly identified as two copies of SSTR6 likely resulting from the salmonid fourth tetraploidization (see Additional file 2, Figure S3).…”

Neuroendocrine regulation of somatic growth in fishes

“…Other research suggests that SSTs are involved in the regulation of growth hormone sensitivity of fish hepatocytes, and can cause a reduction in the levels of GHR expression and IGF-1 biosynthesis and secretion [86,87]. SSTR2 activation is linked to inhibition of pituitary GH release in fish [88]. Additionally, there is an inverse correlation between SST plasma levels and thyroid hormone levels in fish [89].…”

Synthetic paclitaxel-octreotide conjugate reversing the resistance of A2780/Taxol to paclitaxel in xenografted tumor in nude mice

“…Overexpression of MDR1 leads to membrane p-glycoprotein (p-gp) overexpression, which could decrease the intracellular paclitaxel concentration, and results in the reduced inhibitory effect on tumor cells by paclitaxel [31–42]. Studies have shown that, SSTA can suppress MDR1 expression and reverse drug resistance by inhibiting the PI3K/Akt signal pathway when binding to SSTR1A, SSTRR1B and SSTR2 [21]. In our study, POC treatment significantly decreased the mRNA and protein expressions of MDR1 if compared with other treatment group which was consistent with our previous study in vitro .…”