Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Aging-related dysregulation in enteric dopamine and angiotensin system interactions: implications for gastrointestinal dysfunction in the elderly

Pablo Garrido-Gil, Antonio Dominguez-Meijide, Rosario Moratalla, Maria J. Guerra and Jose L. Labandeira-Garcia _

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Oncotarget. 2018; 9:10834-10846. https://doi.org/10.18632/oncotarget.24330

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Abstract

Pablo Garrido-Gil1,2, Antonio Dominguez-Meijide1,2, Rosario Moratalla2,3, Maria J. Guerra1,2 and Jose L. Labandeira-Garcia1,2

1 Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Research Center for Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain

2 Networking Research Centre on Neurodegenerative Diseases, Madrid, Spain

3 Instituto Cajal, Madrid, Spain

Correspondence to:

Jose L. Labandeira-Garcia, email:

Keywords: aged; colon; gut; inflammation; neurotransmitters; Gerotarget

Received: August 15, 2017 Accepted: November 14, 2017 Published: January 29, 2018

Abstract

Gastrointestinal dysfunction is a common problem in the elderly. Aging-related changes in interactions between local dopaminergic and renin-angiotensin systems (RAS) have been observed in the brain, renal and vascular tissues. However, it is not known if these interactions also occur in the gut, and are dysregulated with aging. We showed a mutual regulation between the colonic dopaminergic system and RAS using young and aged mice deficient for major angiotensin and dopamine receptors. Aged rats showed a marked decrease in colonic dopamine D2 receptor expression, together with an increase in angiotensin type 1 (AT1) receptor expression, a decrease in angiotensin type 2 (AT2) receptor expression (i.e. an increase in the RAS pro-inflammatory arm activity), and increased levels of inflammatory and oxidative markers. Aged rats also showed increased levels of colonic dopamine and noradrenalin, and a marked decrease in acetylcholine and serotonin levels. The present observations contribute to explain an aging-related pro-inflammatory state and dysregulation in gastrointestinal function, which may be counteracted by treatment of aged animals with the AT1 receptor blocker candesartan.


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