Open Access

Susanne Damer

• More than 70 years ago, the effects of extracellular adenosine 5'-triphosphate (ATP), a newly identified and purified biomolecule at that time (Fiske and Subbarow, 1925; Lohmann, 1929) were observed by Drury and Szent-Györgyi (1929). Since then, many pharmacological studies were carried out with extracellular adenine nucleotides in various intact organ systems, isolated tissues, and purified cell preparations. Yet it was not until 1972 that Burnstock introduced the concept of "purinergic nerves" and suggested that ATP might fulfil the criteria generally regarded as necessary for establishing a substance as a neurotransmitter, summarised by Eccles (1964): • synthesis and storage of transmitter in nerve terminals Strips of guinea-pig taenia coli (GPTC) were shown to take up large amounts of tritium-labelled adenosine when incubated with tritium-labelled adenosine, adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP) and ATP. The nucleoside was rapidly converted into and retained largely as [ 3 H]-ATP (Su et al., 1971). • release of transmitter during nerve stimulation Spontaneous relaxation of GPTC as well as relaxations induced by nerve stimulation or nicotine, respectively, in the presence of compounds which block adrenergic and cholinergic responses were accompanied by a remarkable increase in release of tritium-labelled material from taenia coli incubated in [ 3 H]-adenosine (Su et al., 1971). • postjunctional responses to exogenous transmitters that mimic responses to nerve stimulation Burnstock et al. (1966) characterised ATP and ADP as the most potent inhibitory purine compounds in the gut and observed that the effects of ATP mimic more closely the inhibitory response of the taenia to non-adrenergic nerve-stimulation than to adrenergic nerve stimulation (Burnstock et al., 1970). enzymes that inactivate the transmitter and/or uptake systems for the transmitter or its breakdown products When ATP was added to a perfusion fluid recycled through the vasculature of the stomach, very little ATP remained, but the perfusate contained substantially increased amounts of adenosine and inosine, as well as some ADP and AMP (Burnstock et al., 1970). • drugs that can produce parallel blocking of potentiating effects on the responses of both exogenous transmitter and nerve stimulation Tachyphylaxis to ATP produced in the rabbit ileum resulted in a consistent depression of responses to non-adrenergic inhibitory nerve stimulation, whereas responses to adrenergic nerve stimulation remained unaffected (Burnstock et al., 1970). Lower concentrations of quinidine reduced and finally abolished relaxation of GPTC induced by noradrenaline (NA) and by adrenergic nerve stimulation. Using higher concentrations of the compound, relaxant responses of GPTC to ATP as well as to non-adrenergic inhibitory nerve stimulation were abolished (Burnstock et al., 1970). ...
• Zu Beginn der 70er Jahre wurde für Adenosin-5'-triphosphat (ATP), das bereits lange als innerhalb der Zelle vorkommender Energieträger bekannt war, eine extrazelluläre Wirkung als Neurotransmitter postuliert. Es dauerte allerdings noch eine Reihe von Jahren, bis die von der Arbeitsgruppe um G. Burnstock aufgestellte Hypothese der "purinergen Nerven" und die damit verbundene Existenz von sogenannten P2-Rezeptoren (früher purinerge Rezeptoren) allgemein anerkannt wurde. Heute besteht kein Zweifel mehr, dass ATP alle der unten genannten Anforderungen an eine als endogener Überträgerstoff innerhalb des vegetativen und zentralen Nervensystems fungierende Substanz erfüllt: • Synthese und Speicherung des entsprechenden Überträgerstoffes, • Freisetzung einer definierten Menge an Transmitter bei einem einlaufenden Aktionspotential, • Rezeptoren für die Reaktion mit dem Transmitter sowie • die rasche Inaktivierung des freigesetzten Neurotransmitters. ...