Structural Stability Analysis of Models of Dopamine Synthesis and D1 Receptor Trafficking in RPT Cells using CRNT
John Justine S. Villar1*, Patrick Vincent N. Lubenia2, Eduardo R. Mendoza3,4,5,6, and Carlene P.C. Pilar-Arceo2
1Department of Computer Science, University of the Philippines Diliman, Quezon City, Philippines
2Institute of Mathematics, University of the Philippines Diliman, Quezon City, Philippines
3Institute of Mathematical Sciences and Physics, University of the Philippines Los Baños, Laguna, Philippines
4Mathematics & Statistics Department, De La Salle University, Manila, Philippines
5Physics Department, Ludwig Maximilians University, Munich, Germany
6Max Planck Institute of Biochemistry, Munich, Germany
Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Dopamine plays an important role in different physiological and metabolic functions, including the control of sodium excretion in the kidney. Studies have shown that there is a positive correlation between a defect in dopamine synthesis and/or dopamine receptor function, and a defect in renal sodium excretion – which may lead to the development of essential hypertension. Specific receptors for dopamine, such as the D1 receptor, have been identified in the various regions within the kidney. It is observed that errors regarding dopamine receptor-G protein coupling and changes in the signaling components may be responsible for the failure of dopamine to increase sodium excretion in hypertensive subjects. In this paper, two symbolic kinetic models of dopamine synthesis and one of dopamine D1 receptor trafficking are presented. The three models are chemical reaction networks constructed and analyzed using Chemical Reaction Network Theory (CRNT), a framework that provides different insights on the static properties of a chemical reaction network regarding the existence of steady states, their multiplicity, and structural stability. It is found that all three networks do not support multiple steady states.
INTRODUCTION
Essential hypertension is a common human disorder characterized by an increase in systemic blood pressure caused by high levels of sodium in the bloodstream. This happens when sodium reabsorption increases in the renal proximal tubule (RPT) cells in the kidney, which in turn occurs when more than the usual amount of sodium is returned to the bloodstream from the glomerular filtrate. Dopamine, an important catecholamine, has been identified to control primary physiological and metabolic processes in the human body – such as locomotion, hormone secretion, behavior– as well as various gastrointestinal, renal, and cardiovascular functions. In the kidney, dopamine is seen as an important regulator of blood pressure, sodium balance, and other metabolic functions. . . . . read more
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