{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:30:58Z","timestamp":1791405058420,"version":"4.3.3"},"reference-count":57,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:p>The role of 3,5,3\u2032-triiodo-l-thyronine (T3) and its metabolite 3,5-diiodo-l-thyronine (T2) in modulating the intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) and endogenous nitric oxide (NO) synthesis was evaluated in pituitary GH<jats:sub>3<\/jats:sub>cells in the absence or presence of extracellular Ca<jats:sup>2+<\/jats:sup>. When applied in Ca<jats:sup>2+<\/jats:sup>-free solution, T2 and T3 increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, in a dose-dependent way, and NO levels. Inhibition of neuronal NO synthase by N<jats:sup>G<\/jats:sup>-nitro-l-arginine methyl ester and l- n<jats:sup>5<\/jats:sup>-(1-iminoethyl)ornithine hydrochloride significantly reduced the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increase induced by T2 and T3. However, while depletion of inositol trisphosphate-dependent Ca<jats:sup>2+<\/jats:sup>stores did not interfere with the T2- and T3-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increases, the inhibition of phosphatidylinositol 3-kinase by LY-294002 and the dominant negative form of Akt mutated at the ATP binding site prevented these effects. Furthermore, the mitochondrial protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone prevented the increases in both [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and NO elicited by T2 or T3. Interestingly, rotenone blocked the early [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increases elicited by T2 and T3, while antimycin prevented only that elicited by T3. Inhibition of mitochondrial Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchanger by CGP37157 significantly reduced the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increases induced by T2 and T3. In the presence of extracellular calcium (1.2 mM), under carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, T2 and T3 increased both [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and intracellular Na<jats:sup>+<\/jats:sup>concentration; nimodipine reduced the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increases elicited by T2 and T3, but inhibition of NO synthase and blockade of the Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>pump by 5-( N-ethyl- N-isopropyl)amiloride prevented only that elicited by T3; and CB-DMB, bisindolylmaleimide, and LY-294002 (inhibitors of the Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchanger, PKC, and phosphatidylinositol 3-kinase, respectively) failed to modify the T2- and T3-induced effects. Collectively, the present results suggest that T2 and T3 exert short-term nongenomic effects on intracellular calcium and NO by modulating plasma membrane and mitochondrial pathways that differ between these iodothyronines.<\/jats:p>","DOI":"10.1152\/ajpendo.00389.2011","type":"journal-article","created":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T04:44:34Z","timestamp":1331700274000},"page":"E1419-E1430","source":"Crossref","is-referenced-by-count":20,"title":["Intracellular and plasma membrane-initiated pathways involved in the [Ca<sup>2+<\/sup>]<sub>i<\/sub>elevations induced by iodothyronines (T3 and T2) in pituitary GH<sub>3<\/sub>cells"],"prefix":"10.1152","volume":"302","author":[{"given":"Adelaide","family":"Del Viscovo","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze per la Biologia, la Geologia e l'Ambiente, Universit\u00e0 del Sannio, Benevento, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Secondo","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples \u201cFederico II\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Esposito","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples \u201cFederico II\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Goglia","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze per la Biologia, la Geologia e l'Ambiente, Universit\u00e0 del Sannio, Benevento, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Moreno","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze per la Biologia, la Geologia e l'Ambiente, Universit\u00e0 del Sannio, Benevento, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorella M. 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