Hydroxylamine blocks adenosine A1 receptor-mediated inhibition of synaptic transmission in rat hippocampus

Adenosine Mediates Decreased Cerebral Metabolic Rate and Increased Cerebral Blood Flow During Acute Moderate Hypoxia in the Near‐Term Fetal Sheep

“…Growing evidence points to adenosine, an endogenously produced purine nucleoside, as a mediator of both increased cerebral blood flow and decreased cerebral metabolic rate during hypoxic stress (Blood et al 2002). Plasma and intracerebral adenosine concentrations increase during hypoxia in the fetal sheep (Kjellmer et al 1989; Koos et al 1997; Suzuki & Power, 1999), newborn lamb (Laudignon et al 1991), and adult rat (Winn et al 1981 b ; Van Wylen et al 1986), in association with an inhibition of neuronal activity (Fowler et al 1999). Intravenous administration of theophylline, a non‐specific adenosine receptor antagonist, abolishes increases in cortical blood flow during hypoxia in the fetal sheep (Blood et al 2002).…”

“…Intravenous administration of theophylline, a non‐specific adenosine receptor antagonist, abolishes increases in cortical blood flow during hypoxia in the fetal sheep (Blood et al 2002). In adult animals adenosine, acting on the adenosine A 1 receptor, suppresses cerebral metabolic rate during hypoxia/asphyxiain hippocampal slices (Croning et al 1995; Jin & Fredholm, 1997; Fowler et al 1999) and during severe asphyxia in vivo (Hunter et al 2003 c ). In the fetal sheep, breathing movements are inhibited by hypoxia, an adaptation that is abolished by adenosine‐receptor blockade at the level of the thalamus (Koos et al 1994 a ; Chau & Koos, 1999).…”

Physiological Neuroprotective Mechanisms in Natural Genetic Systems: Therapeutic Clues for Hypoxia-Induced Brain Injuries

“…In support of this idea, electrophysiological evidence reveals that failure of ATPase causes anoxic depolarization through some intermediate event, such as Na + -induced cell swelling (Rufini et al 2009). To clarify the direct relationship between anoxic depolarization and ATP levels, synaptic transmission analysis in rat hippocampus revealed that first, Na + influx plays a relatively larger role in ATP consumption during hypoxia than Ca 2+ influx; second, anoxic depolarization imposes a large and rapid drop in ATP levels (Fowler et al 1999). Taken together, it then implies that depolarization and increased sodium concentration during hypoxia seem to account for a significant portion of the neuronal damage induced by hypoxia that eventually leads to both necrotic and apoptotic processes (Reshef et al 2000;Gonchar and Mankovskaya 2009).…”

“…Precisely, it has been shown that A1 receptor stimulation inhibits the brain's electrical activity through K + channel activation (direct coupling via G-proteins to ion channels) and/or by inhibiting the high-voltage-activated Ca 2+ channels (Fowler et al 1999;Reshef et al 2000). Extracellular adenosine plays a role in the reduction of K + influx (channel arrest) that occurs in a brain that was subjected to chronic hypoxia (Reshef et al 2000).…”

Clinical Neuroprotection Against Tissue Hypoxia During Brain Injuries; The Challenges and the Targets

“…Studies in young sheep and adult rats indicate that intracerebral A1 concentrations increased during hypoxia. The specific role of A1 was linked to its ability to inhibit neuronal activity (Fowler et al, 1999). In vitro studies on hippocampal slices indicate that elevation of A1 receptors is associated with hypoxia (Jin and Fredholm, 1997), and severe asphyxia in vivo (Hunter et al, 2003c), following inhibition of neuronal activity.…”