Novel role of macrophage migration inhibitory factor in angiotensin II regulation of neuromodulation in rat brain

Endocrinology
S BuscheC Sumners

Abstract

Previously we determined that angiotensin II (Ang II) activates neuronal AT(1) receptors, located in the hypothalamus and the brainstem, to stimulate noradrenergic pathways. To link Ang II to the regulation of norepinephrine metabolism in neurons cultured from newborn rat hypothalamus and brainstem we have used cDNA arrays for high throughput gene expression profiling. Of several genes that were regulated, we focused on macrophage migration inhibitory factor (MIF), which has been associated with the modulation of norepinephrine metabolism. In the presence of the selective AT(2) receptor antagonist PD123,319 (10 microM), incubation of cultures with Ang II (100 nM; 1-24 h) elicited an increase in MIF gene expression. Western immunoblots further revealed that Ang II (100 nM; 1-24 h) increased neuronal MIF protein expression. This effect was inhibited by the AT(1) receptor antagonist losartan (10 microM), the PLC inhibitor U-73122 (10 or 25 microM), the PKC inhibitor chelerythrine (10 microM), and the Ca(2+) chelator 1,2-bis-[2-aminophenoxy]-ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (10 microM). Taken together with our observation that MIF is expressed in the terminal fields of noradrenergic neurons (hypothalam...Continue Reading

References

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Citations

Mar 13, 2003·Kidney International·Edwina K RiceDavid J Nikolic-Paterson
May 16, 2002·Clinical and Experimental Pharmacology & Physiology·Colin SumnersMingyan Zhu
Jul 1, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hongwei LiColin Sumners
Mar 16, 2007·American Journal of Physiology. Cell Physiology·Tomokazu MatsuuraColin Sumners
Mar 22, 2019·Nature Reviews. Cardiology·Laura CalvilloGianfranco Parati
May 10, 2003·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Melissa A Fleegal, Colin Sumners
Mar 11, 2005·Neurochemical Research·O A CherepkovaB Ya Gurvits
Feb 11, 2004·Progress in Biophysics and Molecular Biology·S KasparovJ F R Paton
Sep 26, 2002·The Journal of Biological Chemistry·Hong LiaoRobert A Mitchell
Oct 6, 2009·Biochemical and Biophysical Research Communications·Rachael A Harrison, Colin Sumners

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