Effects of pasireotide (SOM230) on protein turnover and p70S6 kinase-S6 ribosomal protein signaling pathway in rat skeletal muscle cells

Excerpt

The multiligand somatostatin (SS-14) analog pasireotide (SOM230) has been approved to treat patients harboring ACTH-secreting pituitary adenomas [1]. The higher binding affinity of pasireotide for the sst5 receptor subtype compared to the first generation analogs, octreotide and lanreotide [2, 3], joint to a functional selectivity of distinct SS-14 analogs at sst2 receptor [4, 5], suggest to explore its potential effects on extra-pituitary tissues. Indeed, SS-14 receptor subtypes (sst1–5) are heterogeneously expressed in different tissues [6]. There is evidence that SS-14 is transiently expressed in motoneurons during early postnatal development in the rat and the expression of sst2, sst3, and sst4 receptor subtypes in rat skeletal muscle decreases progressively during development [7]. To our knowledge, the hypothesis that stable SS-14 analogs may exert some direct effects in skeletal muscle cells has not been tested yet. These effects, if any, would certainly be of interest as to the use of pasireotide in the treatment of diseases entailing an excess of catabolism and loss of lean mass. …