Background: Systemic infusion of somatostatin (SRIF) induces many physiological changes in human and rodent kidneys, including alterations in glomerular filtration, solute transport, and water clearance. Although somatostatin can bind to five different G-protein coupled receptors (SSTRs), only SSTR1 and SSTR2A proteins have been described convincingly in rat and/or human kidneys. Both are expressed primarily in collecting ducts, despite clear evidence that somatostatin also can bind to proximal tubules. Our aim was to characterize the expression of somatostatin receptors three to five in adult mouse kidneys.
Methods: Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed followed by Southern blotting on mouse kidney RNA for SSTR3, SSTR4, and SSTR5. Immunohistochemistry and dual-labeling immunofluorescence also were performed to localize the receptors in the kidney.
Results: Messenger RNA was detected for somatostatin receptors 3 to 5 in the mouse kidney by RT-PCR, with confirmation by Southern blotting. By immunohistochemistry and dual-labeling immunofluorescence, the proteins for all three receptors were abundantly expressed, but exclusively localized to the proximal tubules. SSTR3 was present in intracellular granules, while SSTR4 and SSTR5 were expressed on the lumenal membranes of the tubules.
Conclusions: Expression of SSTR3, SSTR4, and SSTR5 in mouse proximal tubules complements the expression of SSTR1 and SSTR2 in collecting ducts as seen in other species. Taken together, the kidney is one of few organs expressing all five somatostatin receptors outside of the nervous system and pancreas.
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Sci Rep
January 2025
Department of Radiology, The University of Alabama at Birmingham, Birmingham, USA.
Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake.
View Article and Find Full Text PDFActa Physiol (Oxf)
February 2025
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Aim: Somatostatin from pancreatic δ-cells is a paracrine regulator of insulin and glucagon secretion, but the release kinetics and whether secretion is altered in diabetes is unclear. This study aimed to improve understanding of somatostatin secretion by developing a tool for real-time detection of somatostatin release from individual pancreatic islets.
Methods: Reporter cells responding to somatostatin with cytoplasmic Ca concentration ([Ca]) changes were generated by co-expressing somatostatin receptor SSTR2, the G-protein Gα15 and a fluorescent Ca sensor in HeLa cells.
bioRxiv
January 2025
Department of Neurosciences and Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
The medial habenula (MHb)-interpeduncular nucleus (IPN) pathway plays an important role in information transferring between the forebrain and the midbrain. The MHb-IPN pathway has been implicated in the regulation of fear behavior and nicotine addiction. The synapses between the ventral MHb and the IPN show a unique property, i.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Radioactive prostate-specific membrane antigen (PSMA)-targeting agents are clinically useful for the diagnosis and treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Neuroendocrine-differentiated prostate cancer (NEPC), a highly aggressive subtype that is strongly associated with a poor clinical prognosis, may present with reduced PSMA expression and evade detection with PSMA-targeted agents. Several studies have shown elevated uptake of somatostatin receptor 2 (SSTR2) ligands in PSMA-negative NEPC.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology &Metabolism, West China Hospital, Sichuan University, Chengdu 610041.
Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease.
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