Somatostatin modulates PI3K-Akt, eNOS and NHE activity in the ciliary epithelium.
Somatostatin (SST) is a biologically active peptide produced in neuroendocrine cells. In the present study, we provide evidence of pro-SST and SST receptor (SSTR1 and 2A) mRNA expression in ocular ciliary epithelium (CE). SST or SST-like immunoreactivity was detected by radioimmunoassay in tissue extract from ciliary processes and in aqueous humor. The distinct immunolabeling of CE with SST and proprotein convertases PC1 and PC2 antibodies suggested a tissue and cell-specific processing of pro-SST. SST (10(-8) to 10(-4)M) added exogenously to the CE, elicited the following effects: (i) a dose-dependent attenuation of Na+/H+-exchanger (NHE) activity; (ii) up to a two-fold increase phosphorylation of p-Akt-Ser473 and of p-eNOS-Ser617, and (iii) lack of response on intracellular cyclic GMP production. LY294002, a PI3K-inhibitor, blocked SST-induced p-Akt-Ser473 and partially p-eNOS-Ser617, however, it did not reverse SST-induced NHE attenuation. Collectively, these results suggested involvement of SST in multiple intracellular signaling pathways in the CE.
Ghosh
Sikha
S
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA.
Choritz
Lars
L
Geibel
John
J
Coca-Prados
Miguel
M
D000818:Animals; D002417:Cattle; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D052250:Nitric Oxide Synthase Type III; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D000254:Sodium-Potassium-Exchanging ATPase; D013004:Somatostatin