The widespread expression of morphine by plants, invertebrate and vertebrate cells/organ systems strongly indicates a high level of evolutionary conservation of morphine and related morphinan alkaloids as essential chemical factors required for normal growth and development. The prototype catecholamine dopamine (DA) serves as an essential chemical intermediate in morphine biosynthesis both in plants and animals. We surmise primordial, multi-potential cell types, before the emergence of specialized plant and animal cells/organ systems, required selective mechanisms to limit their responsiveness to environmental noise. Accordingly, cellular systems that emerged with the potential for recruitment of the free radical gas nitric oxide (NO) as a multi-faceted autocrine/paracrine signaling molecule were provided with extremely positive evolutionary advantages. Endogenous "morphinergic" in concert with NO-coupled signaling systems have evolved as autocrine/paracrine regulators of metabolic homeostasis, energy metabolism, mitochondrial respiration and energy production. Basic physiological processes involving "morphinergic"/NO-coupled regulation of mitochondrial function, with special emphasis on the cardiovascular system, are critical to all organismic survival. Critical to this concept may be the phenomenon of mitochondrial enslavement in eukaryotic evolution via morphine.

Keywords: Receptors, Opioid, mu - metabolism, Nitric Oxide - metabolism, Models, Biological, Morphine - metabolism, Mitochondria - metabolism, Catecholamines - metabolism, Cardiovascular System - metabolism, Biological Evolution