Purinergic signalling

The Chief Editor of Acta Physiologica earned his degree at the I. Physiologisches Institut in Heidelberg. He is right now writing these lines in Hessische Str. 3–4 in Berlin. Who cares? And what does this have to do with purines in physiology, a topic so hot that our journal dedicated a whole issue to it (Fredholm & Verkhratsky 2010)? Little did I know at the time in Heidelberg that the enormous desk I was sitting at had once been the desk of Albrecht Karl Martin Leonhard Kossel (Had I known, our laboratory dogs would probably not have been allowed to relieve their bowels there as often). Kossel discovered the nitrogenous compounds purine and pyrimidine in the resolvent of the nucleic acid. He separated two different purines: adenine and guanine and three different pyrimidines: thymine (separated firstly), cytosine and uracil (Anon 2007, http://www.nobelkepu.org.cn/english/physiology/ 134556.shtml). For this, Kossel was awarded the Nobel Prize in 1910. In the late 19th century, Kossel joined the famous physiologist Emil Du Bois-Reymond in Berlin. And as you may already anticipate, their laboratory was situated in the building I am now sitting. Looking out of the window to the left, the previous Chemistry Department appears. There, in the Chemistry Department, once sat Hermann Emil Fischer, who coined the name purine (purum uricum) in 1884 and was awarded the Nobel Prize in 1902. Finally, in 1929, Hans Karl Heinrich Adolf Lohmann discovered ATP. Naturally, his office in Berlin was just down the hall. Realizing all this can cause acute academic insignificance syndrome! Also in 1929, Alan Drury and Albert Szent-GyÎrgyi proposed that purines are signalling molecules. Geoffrey Burnstock, the man who built the concept of adenosine triphosphate (ATP) as a transmitter molecule, and contributed to the special issue in Acta Physiologica (Burnstock et al. 2010), was born, naturally, in 1929. Purinergic signalling is a true strength of Acta Physiologica (Oxford). As pointed out by Fredholm & Verkhratsky (2010), only water is involved in a higher number of chemical reactions than ATP. Given its high concentration in the cytosol, it does not surprise that ATP acts also as a signalling molecule. When cells take harm, surrounding ATP concentration increases. ATP then acts as an extracellular signal, such as in the gut (Kaunitz & Akiba 2011) or in the fish gill when hypotonic shock occurs. In this situation, epithelial release of ATP and NaCl secretion is stimulated via purinergic receptors (Marshall 2011). Interestingly, specific ATP sensitive receptors, such as the dorsal root ganglion neurones, inhibit cAMP by a G proteincoupled pathway, suggesting a neuronal expression of a plasmalemmal cAMP receptor (Mamenko et al. 2010). ATP seems so fundamental that even neural stem cell migration involves this pathway (Grimm et al. 2010). Adenosine is a second basic purinergic signalling molecule acting almost universally in the organism (Aliagas et al. 2010, Nilsson et al. 2010, Ribeiro & SebastiÇo 2010, Wang et al. 2010, Yang et al. 2010). It results from ATP degradation. Any increase in energy consumption and, hence, ATP hydrolysis will increase cytosolic adenosine concentration. Adenosine signals ATP breakdown, intraor extracellularly, thereby providing crucial information for complex organisms and may even help regulate apoptosis (Mlejnek & Dolezel 2010). In addition to adenosine, uridine adenosine tetraphosphate (Jankowski et al. 2005, Tolle et al. 2010, Schuchardt et al. 2011), diadenosine tetraphosphate (Schluter et al. 1994, Hoyle & Pintor 2010) and UDP have important roles as signalling molecules (Harden et al. 2010). All these purines are important for cardiovascular physiology (Hansen et al. 2010, Andersen et al. 2011) and pathophysiology (Waldenstrom et al. 2010). Take for instance the kidney, which is a crucial organ for blood pressure control (Guyton 1991). The kidney controls blood pressure by regulating volume and electrolytes, among other mechanisms. ATP supplies the energy to the plasma membrane pumps. Thus, it does not surprise that electrolyte reabsorption is regulated by purinergic receptors (Novak 2011), which help control renal perfusion (Dahl et al. 2011) and sodium homeostasis (Jankowski et al. 2011). In particular, it seems that the renal medulla and its blood supply by the vasa recta determine the long-term blood pressure (Cowley et al. 1995, Makino et al. 2002, Mattson 2003). It seems that nucleotides released from adjacent tubules play an important role in determining vasa recta blood flow (Crawford et al. 2011). To close the circle, Burnstock s interests in purinergic signalling started as he took up his first postdoctoral post with Feldberg (Burnstock 2009). Of course Feldberg s laboratory was here in the Physiological Institute in Berlin (Hessische Str. 3–4). Sadly, he was dismissed in 1933 during the Nazi purge of Jewish scientists and only thanks to the aid of Hill, he could relocate to Britain s National Institute for Medical Research where he welcomed the young Burnstock. Acta Physiol 2012, 204, 3–5