Adenosine in cerebral homeostatic role: Appraisal through actions of homocysteine, colchicine, and dipyridamole

Abstract

Mammalian neocortical tissues were incubated in [14C]adenine-containing fluids and their newly-synthesized adenine derivatives examined after periods of superfusion. Increased [K+] released adenine derivatives from the tissues, a release diminished by homocysteine. Homocysteine acted also to diminish the tissue content of adenosine plus its metabolites hypoxanthine and inosine, while increasing that of S-adenosylhomocysteine. Hypoxia also increased the tissue content and the output of adenosine plus its metabolites, and again homocysteine augmented the S-adenosylhomocysteine. Glutamic acid also increased tissue content and output of adenosine and derivatives, an action diminished by homocysteine and associated with augmented S-adenosylhomocysteine. Colchicine or dipyridamole did not prevent augmentation of S-adenosylhomocysteine by the reagents described; the sequence from adenosine phosphates to S-adenosylhomocysteine is concluded to be intracellular and not to involve extracellular formation of precursor adenosine. Adenosine displayed properties consistent with its being involved in two distinct categories of homeostasis, and also with its exerting an inhibitory tone in normal cerebral systems.

Control and Function of the Homeostatic Sleep Response by Adenosine A1Receptors

“…Adenosine is the endogenous ligand for the AdoA1R and its extracellular concentration increases whenever the ratio of metabolite availability to metabolite demand decreases (Greene and Haas, 1991;Dunwiddie and Masino, 2001;McIlwain and Poll, 1986). An AdoA1R mediated inhibitory tone, present under physiological conditions, is positively modulated with a slow time constant in response to maintained increases in excitatory synaptic glutamate release as occurs with maintained waking (Brambilla et al, 2005a).…”

NMDA receptor-mediated extracellular adenosine accumulation is blocked by phosphatase 1/2A inhibitors

“…Adenosine is a ubiquitous neuromodulator in the central nervous system [18,23,42]. Its action is mediated by adenosine A 1 , A 2A , A 2B , and A 3 receptors.…”

NMDA receptor‐mediated extracellular adenosine accumulation in rat forebrain neurons in culture is associated with inhibition of adenosine kinase

“…Adenosine is an inhibitory neuromodulator in the central nervous system (Dunwiddie, 1985; McIlwain & Poll, 1986; Greene & Haas, 1991). It decreases neuronal firing (Phillis et al ., 1974) and inhibits the release of a number of neurotransmitters including glutamate (Dolphin & Archer, 1983; Brand et al ., 2001), aspartate (Burke & Nadler, 1988), acetylcholine (Jackisch et al ., 1984), and γ‐aminobutyric acid (Bonci & Williams, 1996) by activating the A1 receptor.…”