In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 302, No. 11 ( 2012-06-01), p. E1419-E1430
Abstract:
The role of 3,5,3′-triiodo-l-thyronine (T3) and its metabolite 3,5-diiodo-l-thyronine (T2) in modulating the intracellular Ca 2+ concentration ([Ca 2+ ] i ) and endogenous nitric oxide (NO) synthesis was evaluated in pituitary GH 3 cells in the absence or presence of extracellular Ca 2+ . When applied in Ca 2+ -free solution, T2 and T3 increased [Ca 2+ ] i , in a dose-dependent way, and NO levels. Inhibition of neuronal NO synthase by N G -nitro-l-arginine methyl ester and l- n 5 -(1-iminoethyl)ornithine hydrochloride significantly reduced the [Ca 2+ ] i increase induced by T2 and T3. However, while depletion of inositol trisphosphate-dependent Ca 2+ stores did not interfere with the T2- and T3-induced [Ca 2+ ] i 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 2+ ] i and NO elicited by T2 or T3. Interestingly, rotenone blocked the early [Ca 2+ ] i increases elicited by T2 and T3, while antimycin prevented only that elicited by T3. Inhibition of mitochondrial Na + /Ca 2+ exchanger by CGP37157 significantly reduced the [Ca 2+ ] i 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 2+ ] i and intracellular Na + concentration; nimodipine reduced the [Ca 2+ ] i increases elicited by T2 and T3, but inhibition of NO synthase and blockade of the Na + /H + 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 + /Ca 2+ 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.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00389.2011
Language:
English
Publisher:
American Physiological Society
Publication Date:
2012
detail.hit.zdb_id:
1477331-4
SSG:
12
