Date of Award
Somatostatin, Intracellular Signaling, Human Bronchial Smooth Muscle Cells
Somatostatin (somatotropin release inhibitory factor; SRIF), is an endogenous peptide family that controls cellular secretion and proliferation. While SRIF's cognate receptors and associated actions have been clearly identified in a range of tissues, such as the endocrine, gastrointestinal and immune systems, a role in human lung physiology remains unknown. Using primary human bronchial smooth muscle cells (hBSMC) as a model for studying SRIF's actions, we have investigated whether SRIF receptors are present and functional in human bronchial smooth muscle. Reverse transcriptase- polymerase chain reaction (RT-PCR) analysis ofhBSMC total mRNA demonstrated the presence of the sst, receptor subtype, providing a molecular target for SRIF action. SRIF's functional effects on intracellular signaling were confirmed by Western blotting with phospho-specific antibodies for the extracellular regulated kinases 1/2 (ERKl/2). Using a nonpeptidyl sst, selective agonist, L-779,976, we demonstrated an acute inhibition (50 ± 5%) of basal ERKl/2 phosphorylation. In addition, L-779,976-treated hBSMC cell membranes showed a 2.4-fold increase in tyrosine phosphatase activity, which was abolished by the selective tyrosine phosphatase inhibitor sodium vanadate. Furthermore, a 48 h treatment with 100 nM L-779,976 suppressed hBSMC proliferation by 30%. Taken together, our results show that the hBSMC is a direct target of SRIF' s antiproliferative activity. We propose that SRIF's actions in controlling lung smooth muscle cell proliferation could prove therapeutically useful in chronic asthma where inappropriate hBSMC proliferation plays a role.
Alfonzo, Michael J., "Somatostatin Regulates Intracellular Signaling in Human Bronchial Smooth Muscle Cells" (2005). Seton Hall University Dissertations and Theses (ETDs). 2337.