Participation of glucose transporters on atrial natriuretic peptide-induced glucose uptake by adult and neonatal cardiomyocytes under oxygenation and hypoxia Verónica Sosa, Roxana Carbó, Verónica Guarner ⁎ Physiology Department National Institute of Cardiology “Ignacio Chávez”, Mexico D.F. Received 18 January 2007; received in revised form 18 April 2007; accepted 20 April 2007 Available online 30 April 2007 Abstract Natriuretic peptides, beside their endocrine actions, have paracrine functions which include regulating glucose uptake and metabolism. Atrial natriuretic peptide (ANP) actions are mediated by cGMP which is implicated in the metabolic adaptation of glucose metabolism to oxygen deprivation in the heart. Although, it has been reported that ANP increases glucose uptake, cGMP decreases it. The aim of the present paper was to evaluate the role of the glucose transporters 1 and 4 (GLUTS), in glucose uptake produced by ANP in fatty acid-dependent adult cardiomyocytes and glucose-dependent neonatal cardiomyocytes under oxygenation and hypoxia, which reverts adult metabolism to glucose-dependent. We also explored if the calcium–calmodulin complex participates in ANP-induced increase in glucose uptake. Neonatal cells had a higher glucose uptake than adult cells and GLUT 1 participated in basal uptake in both cell types. Hypoxia increased glucose uptake in adult cardiomyocytes but not in neonatal cells and this increase in glucose uptake was mediated by GLUT4. ANP increased glucose uptake in both adult and neonatal myocytes, under oxygenation and hypoxia, and GLUT4 favored this increase. Neonatal cells were less sensitive to ANP. Trifluoperazine, a calcium– calmodulin blocker, inhibited the ANP-induced increase in glucose uptake. This suggests that ANP promotes GLUT 4 calcium-mediated recruitment to the cell membrane. In conclusion, glucose uptake regulation is one of the paracrine metabolic effects of ANP in adult and neonatal cardiomyocytes under oxygenation and hypoxia. This effect of this peptide could explain the beneficial effects found in the internal medicine and surgical fields. © 2007 Elsevier B.V. All rights reserved. Keywords: ANP; Glucose transporters; Glucose uptake; Hypoxia; Cardiomyocytes 1. Introduction Natriuretic peptides are a family of polypeptide mediators exerting numerous actions in cardiovascular homeostasis. The endocrine effects of atrial natriuretic peptide (ANP) on fluid homeostasis and blood pressure, especially in conditions characterized by left ventricular dysfunction, are well recognized and extensively researched. Furthermore, there is accumulating evidence that in addition to endocrine actions, natriuretic peptides exhibit important autocrine and paracrine functions within the heart and coronary circulation (D'Souza et al., 2004) which include metabolic effects such as stimulating lipolysis (Sengenes et al., 2005) and regulating glucose uptake and metabolism particularly during hypoxia (Kudoh et al., 2002). Secretion of atrial natriuretic peptide (ANP) and tissue responses to it, are modified by cellular metabolism (Toth et al., 1994; Mc Kenna et al., 2000). Hyperglycemia increases the expression of the messenger RNA of ANP and insulin increases secretion of ANP but reduces peripheral tissue responses to it (Nannipieri et al., 2002, Nosadini et al., 1989). ANP actions can be ascribed to guanylyl cyclase activation because its receptor has an intracellular guanylyl cyclase domain. This activation promotes the elevation of the intracellular second messenger cGMP exerting diverse physiological effects through activation of cGMP-dependent protein kinases (Wollert et al., European Journal of Pharmacology 568 (2007) 83 – 88 www.elsevier.com/locate/ejphar ⁎ Corresponding author. Departamento de Fisiología, Instituto Nacional de Cardiología “Ignacio Chávez”. Juan Badiano 1, col. Sección XVI, Tlalpan, México, D.F. 14080, México. Tel.: +52 5 573 29 11x1278; fax: +52 5 573 09 26. E-mail address: vguarner@yahoo.com (V. Guarner). 0014-2999/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2007.04.040