Abstract

Coordinated expression of evolutionarily conserved SLC and ABC membrane transporters maintains homeostatic balance within and between organs/organ systems. The primary physiological functions of these transporters is to 1) handle endogenous metabolites and toxins, 2) distribute and maintain effective intraorgan concentrations of nutrients and antioxidants, and 3) maintain overall systemic homeostasis. These processes/pathways involve the transcellular movement of solutes across epithelial barriers by "matching" pairs of SLC and ABC transporters. As described in the "Remote Sensing and Signaling Hypothesis"(Ahn and Nigam, 2009; Kaler et al., 2007; Kaler et al., 2006; Monte et al., 2004; Nigam et al., 2007), such coordinated transporter networks maintain and regulate homeostasis either through carrier sensing/signaling in different cells and/or organs, or via the handling/sensing and signaling of substrates by a set of carriers with shared substrate preferences. In addition, these transporter networks are sensitive to environmental changes (i.e., substrate imbalance and injury) and we argue that they are integral components of overall regulatory mechanisms including hormones, growth factors and pheromones, and their receptors. Uric acid and urate, carnitine, prostaglandins, cGMP, odorants and enterobiotic metabolites are discussed. Xenobiotics hitchhike and/or potentially highjack endogenous carrier systems sometimes leading to toxic effects. We postulate that transporter proteins are key in regulating concentration gradients and/or maintaining the metabolic composition of body compartments in the mature and possibly developing organism. Moreover, these transporters may be crucial in the metabolism-related communication between organisms, and thus in the subtle dynamics of ecological interactions and maintenance of various biomes.