{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:59:35Z","timestamp":1772812775900,"version":"3.50.1"},"reference-count":69,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:p>Stable somatostatin analogues and dopamine receptor agonists are the mainstay for the pharmacological treatment of functional pituitary adenomas; however, only a few cellular assays have been developed to detect receptor activation of novel compounds without disrupting cells to obtain the second messenger content. Here, we adapted a novel fluorescence-based membrane potential assay to characterize receptor signaling in a time-dependent manner. This minimally invasive technique provides a robust and reliable read-out for ligand-induced receptor activation in permanent and primary pituitary cells. The mouse corticotropic cell line AtT-20 endogenously expresses both the somatostatin receptors 2 (sst2) and 5 (sst5). Exposure of wild-type AtT-20 cells to the sst2- and sst5-selective agonists BIM-23120 and BIM-23268, respectively, promoted a pertussis toxin- and tertiapin-Q-sensitive reduction in fluorescent signal intensity, which is indicative of activation of G protein-coupled inwardly rectifying potassium (GIRK) channels. After heterologous expression, sst1, sst3, and sst4 receptors also coupled to GIRK channels in AtT-20 cells. Similar activation of GIRK channels by dopamine required overexpression of dopamine D2 receptors (D2Rs). Interestingly, the presence of D2Rs in AtT-20 cells strongly facilitated GIRK channel activation elicited by the sst2-D2 chimeric ligand BIM-23A760, suggesting a synergistic action of sst2 and D2Rs. Furthermore, stable somatostatin analogues produced strong responses in primary pituitary cultures from wild-type mice; however, in cultures from sst2 receptor-deficient mice, only pasireotide and somatoprim, but not octreotide, induced a reduction in fluorescent signal intensity, suggesting that octreotide mediates its pharmacological action primarily via the sst2 receptor.<\/jats:p>","DOI":"10.1210\/me.2015-1241","type":"journal-article","created":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T18:41:52Z","timestamp":1457721712000},"page":"479-490","source":"Crossref","is-referenced-by-count":31,"title":["Research Resource: Real-Time Analysis of Somatostatin and Dopamine Receptor Signaling in Pituitary Cells Using a Fluorescence-Based Membrane Potential Assay"],"prefix":"10.1210","volume":"30","author":[{"given":"Thomas","family":"G\u00fcnther","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, D-07749 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Culler","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, D-07749 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Schulz","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, D-07749 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"issue":"2","key":"2020071613184031000_B1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11154-008-9107-z","article-title":"Medical therapy of pituitary adenomas: effects on tumor shrinkage","volume":"10","author":"Colao","year":"2009","journal-title":"Rev Endocr Metab Disord"},{"issue":"5463","key":"2020071613184031000_B2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1126\/science.288.5463.154","article-title":"Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity","volume":"288","author":"Rocheville","year":"2000","journal-title":"Science"},{"issue":"6","key":"2020071613184031000_B3","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1210\/endo-121-6-2177","article-title":"Somatostatin receptors on pituitary somatotrophs, thyrotrophs, and lactotrophs: pharmacological evidence for loose coupling to adenylate cyclase","volume":"121","author":"Epelbaum","year":"1987","journal-title":"Endocrinology"},{"issue":"1","key":"2020071613184031000_B4","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0306-4522(93)90119-Z","article-title":"Bromocriptine, a dopamine D2 receptor agonist, inhibits adenylyl cyclase activity in rat olfactory epithelium","volume":"57","author":"Mania-Farnell","year":"1993","journal-title":"Neuroscience"},{"issue":"5","key":"2020071613184031000_B5","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1023\/A:1006988603199","article-title":"Adenylyl cyclase interaction with the D2 dopamine receptor family; 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