Introduction 5 in situ 1 Vagusstoff via 1 Fig. 1 −1 −13 −1 −12 −1 19  It was evident that for successful measurement of acetylcholine, the identification of the interfering substance, and its removal from the solution, had to be achieved. At this stage the basic question became: what substance(s) released from active skeletal muscle could possibly stimulate the frog heart? A “blunderbuss” approach was adopted, by perfusing through the heart as many available substances, known to exist in muscle, to see if any of them produced the stimulatory effect. The purine monophosphates and adenosine were eliminated since they did not stimulate the heart. Electrolyte changes, including an elevated potassium level, were also ruled out. Changes in calcium levels were hardly detectable in the bathing solution. 3 Fig. 2 −1 6 17  Indirect versus direct muscle stimulation directly Identification procedures Identification of the stimulatory substance was established using three procedures: gel filtration, enzyme action of apyrase, and firefly tail luminescence. Gel filtration chromatography 2 Fig. 3 Vertical interrupted line −6 −1 −6 −1 6  Incubation with apyrase 61 The luciferin/luciferase test for ATP 38 Photinus pyralis 18 Procedures applied to perfused frog musculature 1 23 −1 −1 −1 −1 6 Table 1 a Hz −1 −1 −1 −1 1 4.0 240 2 1.5 180 5 1.4 420 10 3.0 1,800 a 23 Procedures applied to human muscle in vivo 20 21 4 22 Fig. 4 a −6 −1 b c 22  Sequelae 48 56 membrane depolarization, hypoxia mechanical distortion 25 Association of ATP release from depolarizing membrane 1 32 33 40 31 63 following 25 Hypoxia 4 24 26 8 nucleoside nucleotide 36 44 12 63 Mechanical distortion 59 10 45 47 54 30 27 55 62 39 Perspectives Towards the search for an ATP channel in the plasma membrane 7 4 34 52 60 51 1 Exercise and circulating purines 43 15 11 2 Use of ATP in cancer therapy 49 50 14 35 3 5 Fig. 5 a b top bottom 3  Protective effect of ATP against ischemia 9 37 41 58 Protective effect of ATP in radiation therapy 57 2 Aging and extracellular ATP levels 28 enhanced 29 1 46 31 42 13 53 Epilogos 1 Inspirata accident magis saepe quam quae speres not do