Somatostatin regulates intracellular signaling and proliferation in human bronchial smooth muscle cells.

Abstract

Somatostatin (somatotropin release inhibitory factor; SRIF), is an endogenous peptide family that controls cellular secretion and proliferation. While SRIF’s cognate receptors and associated intracellular signaling have been clearly identified in a range of tissues, such as the endocrine, gastrointestinal and immune systems, a possible role in human lung physiology remains unknown. Using primary human bronchial smooth muscle cells (hBSMC) as a model, we have investigated the presence and function of SRIF receptors in hBSMC. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of hBSMC total mRNA demonstrated the presence of the sst2 receptor subtype, providing a molecular target for SRIF action. SRIF’s intracellular signaling effect on hBSMC was confirmed by Western blotting with phospho-specific antibodies for the extracellular regulated kinases 1/2 (ERK1/2). A nonpeptidyl sst2 selective agonist, L-779,976, acutely inhibited basal ERK1/2 phosphorylation (50 ± 5%), an effect that paralleled a 2.4-fold increase in a vanadate sensitive, cell membrane tyrosine phosphatase activity. Furthermore, 48 h incubation with 100 nM L-779,976 suppressed hBSMC proliferation by 30% when compared to untreated controls. Taken together, our results show that the hBSMC is a direct target of SRIF agonist effects. We propose that SRIF ligands regulate lung smooth muscle cell proliferation, an action that could prove therapeutically useful in conditions where inappropriate hBSMC proliferation plays a role.