Early evolutionary history (from bacteria to hemichordata) of the omnipresent purinergic signalling: A tribute to Geoff Burnstock inquisitive mind

Abstract

Purines and pyrimidines are indispensable molecules of life; they are fundamental for genetic code and bioenergetics. From the very early life forms purines have acquired the meaning of damage-associated extracellular signaller and purinergic receptors emerged in unicellular organisms. Ancestral purinoceptors are P2X-like ionotropic ligand-gated cationic channels ionotropic P2X receptors showing 20 40% of homology with vertebrate P2X receptors; genes encoding ancestral P2X receptors have been detected in Protozoa, Algae, fungi and sponges; they are also present in some invertebrates, but are absent from the genome of insects, nematodes, and higher plants. Plants nevertheless evolved a sophisticated and widespread purinergic signalling system relying on the idiosyncratic purinoceptor P2K1/DORN1 linked to intracellular Ca 2+ signalling. The advance of metabotropic purinoceptors starts later in evolution with adenosine receptors preceding the emergence of P2Y nucleotide and P0 adenine receptors. In vertebrates and mammals the purinergic signalling system reaches the summit and operates throughout all tissues and systems without anatomical or functional segregation.

Adenine-Based Purines and Related Metabolizing Enzymes: Evidence for Their Impact on Tumor Extracellular Vesicle Activities

“…Purines are ubiquitous molecules present in all cells from which they are released in the extracellular environment in physiological conditions; however, purine compounds may be also lost by cells as a consequence of plasma membrane damage upon injury [ 17 ]. The most studied and functionally characterized among these extracellular substances are the adenine-based purines, mainly adenosine triphosphate (ATP) and adenosine (ADO), which behave as intercellular signals, being able to interact with specific receptors belonging to ADO/P1 and ATP/P2 receptors families [ 18 ].…”

ATP signaling in the integrative neural center ofAplysia californica

“…In addition to being the critical energy storage for every cell, ATP acts as one of the most ancient intracellular and intercellular signal molecules (1–3). The possible involvement of ATP in signaling mechanisms was initiated in the 1920s by Drury and Szent-Gyorgyi (4); and then in the 1950s by Holtons (5–7), leading to the concept of purinergic transmission in the 1970s by Burnstock (3,8).…”

“…In addition to being the critical energy storage for every cell, ATP acts as one of the most ancient intracellular and intercellular signal molecules (1–3). The possible involvement of ATP in signaling mechanisms was initiated in the 1920s by Drury and Szent-Gyorgyi (4); and then in the 1950s by Holtons (5–7), leading to the concept of purinergic transmission in the 1970s by Burnstock (3,8). Eventually, in 1983, rapid ATP-gated ion currents were discovered in neurons (9,10) and muscles (11), and specific subtypes of the ligand-gated P2X receptors were identified in the 1990s (12–15).…”

“…Comparative studies established that P2X-type receptors are broadly distributed across many eukaryotic lineages (1,19–21), including the majority of Metazoa (2,3). Across all domains of life, ATP can operate as the bona fide ancient signal molecule (volume transmitter) associated with adaptive reactions to injury and damage (2,3,22).…”

“…In selected evolutionary lineages, P2X receptors were secondarily lost. The list includes higher plants (3), some basal bilaterians such as acoels (22), arthropods and nematodes. For example, Drosophila and C. elegans genomes have no P2X receptors, but other ecdysozoans such as Daphnia , the shrimp Litopenaeus , the tick Boophilus (23), and tardigrades (24) contain one receptor.…”