Repetitive stimulation of adenosine A1 receptors in vivo: changes in receptor numbers, G-proteins and A1 receptor agonist-induced hypothermia.
Adenosine is an important neuromodulator and neuroprotective molecule, which is produced in the brain as a function of neuronal activity, coupling energy expenditure to energy supply. Under conditions of increased need and reduced availability of energy, including hypoxia and prolonged wakefulness, there is an increase in adenosine turnover and adenosine receptor stimulation. The aim of the present study was to examine how repetitive adenosine receptor stimulation affects receptor function and adenosinergic signaling in the brain. Adult male Wistar rats received daily intraperitoneal injections of the adenosine A1 receptor agonist N(6)-cyclopentyladenosine (CPA; 0.25 mg/kg; once per day) and effects on adenosine signaling were established with receptor and G-protein autoradiography. Injections of CPA for 5 consecutive days caused a significant decrease in adenosine A1 receptor numbers in the hippocampus and somatosensory cortex. In contrast, while the amount of adenosine A1 receptor-activated G-proteins was not affected in most regions, a significant increase was found in the somatosensory cortex. On the level of physiological output, CPA-induced hypothermia was significantly attenuated, suggesting a functional desensitization of the A1 receptor system. Taken together, the present findings suggest that repetitive stimulation of the A1 receptors can affect elements of the adenosinergic signaling cascade in the rat brain in a region-specific manner.
Roman
Viktor
V
Department of Molecular Neurobiology, School of Behavioral and Cognitive Neurosciences, University of Groningen, Haren, The Netherlands. v.roman@richter.hu
Keijser
Jan N
JN
Luiten
Paul G M
PG
Meerlo
Peter
P
D000241:Adenosine / Q000031:analogs & derivatives; D058907:Adenosine A1 Receptor Agonists; D000704:Analysis of Variance; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism*; D018709:Statistics, Nonparametric
D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; C048599:N(6)-cyclopentyladenosine; D019204:GTP-Binding Proteins; D000241:Adenosine