Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine transporters in the brains and spinal cords of mice deficient in the mu-opioid receptor gene.
There is a large body of evidence indicating important interactions between the adenosine and opioid systems in regulating pain at both the spinal and supraspinal level. Mice lacking the mu-opioid receptor (MOR) gene have been successfully developed and the animals show complete loss of analgesic responses to morphine as well as differences in pain sensitivity. To investigate if there are any compensatory alterations in adenosine systems in mutant animals, we have carried out quantitative autoradiographic mapping of A(1) and A(2A) adenosine receptors and nitrobenzylthioinosine (NBTI) sensitive adenosine transporters in the brains and spinal cords of wild type, heterozygous and homozygous mu-opioid receptor knockout mice. Adjacent coronal sections were cut from the brains and spinal cords of +/+, +/- and -/- mice for the determination of binding of [3H]DPCPX, [3H]CGS21680 or [3H]NBTI to A(1) and A(2A) adenosine receptors and NBTI-sensitive adenosine transporters, respectively. A small but significant reduction in [3H]DPCPX and [3H]NBTI binding was detected in mutant mice brains but not in spinal cords. No significant change in A(2A) binding was detected in mu-opioid receptor knockout brains. The results suggest there may be functional interactions between mu-receptors and A(1) adenosine receptors as well as NBTI-sensitive adenosine transporters in the brain but not in the spinal cord.
Bailey
Alexis
A
Pharmacology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, UK.
Matthes
Hans
H
Kieffer
Brigitte
B
Slowe
Susan
S
Hourani
Susanna M O
SM
Kitchen
Ian
I
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D005260:Female; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D033703:Nucleoside Transport Proteins; D043705:Receptor, Adenosine A2A; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D018047:Receptors, Purinergic P1 / Q000032:analysis* / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D033703:Nucleoside Transport Proteins; D043705:Receptor, Adenosine A2A; D017450:Receptors, Opioid, mu; D018047:Receptors, Purinergic P1; C444719:adenosine transporter; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine