Peripheral Catecholamine Systems: An Evolutionary Perspective

This essay examines in evolutionary perspective body systems outside the brain that use the catecholamines dopamine (DA), norepinephrine (NE), and epinephrine (EPI) as chemical messengers. Peripheral catecholaminergic systems represent three principal mechanisms by which the brain regulates functions of body organs. DA serves as an autocrine–paracrine factor in the kidneys and splanchnic organs, NE is the neurotransmitter of the sympathetic noradrenergic system (SNS), and EPI is the main hormone secreted by adrenomedullary chromaffin cells. Comparative physiological data suggest that the DA autocrine–paracrine system emerged first, followed by noradrenergic nerve networks culminating in the SNS, with the hormonal sympathetic adrenergic system (SAS) appearing most recently. Examples are presented of the diverse ways these catecholamines have been used during evolution, although the ecological niches that conferred selective advantages remain uncertain. The discussion addresses catecholamine receptors, co-transmission, and interactions between catecholaminergic, neuroendocrine, and immune systems. In humans, the transition to bipedalism likely promoted SNS adaptations for orthostatic regulation of cardiac output as well as for sodium homeostasis and temperature control. The roles of the SAS in organism-wide stress responses, distress, and sympathoadrenal imbalance in fainting are also considered. Concepts such as antagonistic pleiotropy, allostatic load, and autotoxicity are discussed in relation to aging-associated diseases that feature catecholaminergic neurodegeneration. Understanding the phylogeny of peripheral catecholaminergic systems may provide a foundation for Darwinian medicine.