A case of serendipity*

An account is given of how a sensitive bioassay system for measurement of the neurotransmitter acetylcholine serendipitously led to the identification of adenosine triphosphate (ATP) released in vitro from active skeletal muscle. Subsequent application of the identification procedures to exercising human muscle in vivo, cardiac muscle cells in vitro, and human erythrocytes exposed to hypoxia gave rise to the general concept of ATP as a molecule that could influence cell function from the extracellular direction. Mechanisms of ATP release from cells in terms of “trigger” events such as mechanical distortion of the membrane, depolarization of the membrane, and exposure to hypoxia are discussed. Potential therapeutic uses of extracellular ATP in cancer therapy, radiation therapy, and a possible influence upon aging are discussed. Possible roles (distant and local) of extracellular ATP released from muscle during whole body exercise are discussed

ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

A recent study by our lab found high accumulation of extracellular adenosine triphosphate (ATP) in the center of healthy porcine intervertebral discs (IVD). Since ATP is a powerful extracellular signaling molecule, extracellular ATP accumulation may regulate biological activities in the IVD. Therefore, the objective of this study was to investigate the effects of extracellular ATP on the extracellular matrix (ECM) biosynthesis of porcine IVD cells isolated from two distinct anatomical regions: annulus fibrosus (AF) and nucleus pulposus (NP). The ATP treatment significantly promoted the ECM deposition and corresponding gene expression (aggrecan and type II collagen) by both cell types in 3-dimensional agarose culture. A significant increase in ECM accumulation was found in AF cells at a lower ATP treatment level (20 µM) compared to NP cells (100 µM), indicating that AF cells may be more sensitive to extracellular ATP than NP cells. NP cells also exhibited higher ECM accumulation and intracellular ATP than AF cells under Control and treatment conditions, suggesting that NP cells are intrinsically more metabolically active. Moreover, the ATP treatment also augmented the intracellular ATP level in NP and AF cells. Our findings suggest that extracellular ATP not only promotes ECM biosynthesis via molecular pathway but also increases energy supply to fuel that process