Output of [14C]adenine nucleotides and their derivatives from cerebral tissues. Tetrodotoxine-resistant and calcium ion-requiring components

Abstract

1. Neocortical tissues, exposed briefly to [(14)C]adenine and containing over 98% of their (14)C as adenine nucleotides, when superfused with glucose-bicarbonate salines released about 0.1% of their (14)C content/min to the superfusate. 2. Addition of unlabelled adenosine to the superfusing fluid increased the (14)C output three- to four-fold; half-maximal increase was given by about 40mum-adenosine, and reasons are adduced for considering the activity of adenosine kinase to be a major factor in conditioning the (14)C output. Adenosine similarly increased the enhanced (14)C output caused by electrical excitation of the superfused tissue; it brought about only a small increase in tissue glycolysis. 3. Output of (14)C from the [(14)C]adenine-labelled tissues was increased when Ca(2+) was omitted from the superfusing fluids, but electrical stimulation did not then liberate more (14)C. Nevertheless, such tissues still responded to electrical stimulation by increased glycolysis, and their (14)C output again became susceptible to increase by electrical stimulation when Ca(2+) was restored. 4. The six-fold increase in tissue glycolysis caused by electrical excitation was almost completely inhibited by tetrodotoxin at 0.1mum and above, but this was associated with about 50% inhibition only in the output of (14)C from tissues preincubated with [(14)C]adenine. The (14)C-labelled compounds of which output was most inhibited by tetrodotoxin were adenosine, inosine and hypoxanthine whereas output in a nucleotide fraction was little affected.

Activity-Dependent Release of Adenosine Contributes to Short-Term Depression at CA3-CA1 Synapses in Rat Hippocampus

“…An antagonist of adenosine transport did not reduce homosynaptic depression in our experiments, however, consistent with earlier studies of hippocampal heterosynaptic depression (Mitchell et al 1993). Although our evidence is indirect and derived by excluding alternative hypotheses, taken with previous demonstrations of Ca 2ϩ -dependent adenosine release (e.g., Manzoni et al 1994;Pull and McIlwain 1973), we suggest that high-frequency stimulation causes the exocytosis of adenosine-containing vesicles, possibly as a co-transmitter. Ca 2ϩ -dependent release of adenosine from hippocampal interneurons requires NMDA receptor activation (Manzoni et al 1994).…”

Permeabilization of transformed cells in culture by external ATP

“…The authors speculate that ATP (or ADP), which are known to be released from aggregated platelets and injured cells, are regulatory mediators for activation of the mechanism of wound healing in fibroblasts. In fact, ATP is also released from hypoxic cells [18,30], stimulated nerve cells [2,42,80], constricting muscle [11,12] and electrically stimulated brain slices [56,68].…”

Release of Adenosine by Activation of NMDA Receptors in the Hippocampus

“…When applied to brain slices, adenosine exerts a powerful presynaptic inhibition of excitatory synaptic transmission, which is mediated by Al receptors (2). Furthermore, the concentration of extracellular adenosine is increased during hypoxia (3), synaptic stimulation (4), and the application of glutamate (5,6). The NMDA subtype of glutamate receptor is necessary for glutamate-evoked elevation of the concentration of adenosine, and this effect is Ca2+dependent (6).…”