Activation of metabotropic glutamate receptors increases extracellular adenosine in vivo.
In order to identify the mechanisms that would lead to increased levels of the inhibitory neuromodulator adenosine in the brain, we tested metabotropic glutamate receptor agonists for their ability to increase extracellular adenosine in the cortex of unanesthetized rat using in vivo microdialysis. The group I/II metabotropic glutamate receptor agonist trans-(+/-)- 1-amino-(1S,3R)-cyclopenyanedicarboxylic acid (I mM) increased extracellular adenosine as did the specific group I agonist (S)- 3,5-dihydroxyphenylglycine (DHPG; 1 mM). The evoked increase of adenosine by 1 mM DHPG was reduced by the group I antagonist (RS)- 1-aminoindan-1,5,-dicarboxylic acid. Activation of group II or III metabotropic receptors did not affect extracellular adenosine. These results suggest that activation of group I metabotropic receptors contributes to elevated extracellular adenosine levels in vivo.
Bennett
H J
HJ
Department of Anatomy, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
White
T D
TD
Semba
K
K
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D008734:Methoxyhydroxyphenylglycol; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000241:Adenosine; C010117:3,4-dihydroxyphenylglycol