Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine transporters in the brains of mice deficient in the preproenkephalin gene

• Published in: Brain research Vol. 1025; no. 1; pp. 1 - 9
• Main Authors: Bailey, Alexis, Weber, Daniel, Zimmer, A., Zimmer, A.M., Hourani, Susanna M.O., Kitchen, Ian
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 29.10.2004; Amsterdam Elsevier; New York, NY
• Subjects: A 1 receptor; A 2A receptor; Animals; Autoradiography; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Enkephalin knockout; Enkephalins - biosynthesis; Enkephalins - deficiency; Enkephalins - genetics; Fundamental and applied biological sciences. Psychology; Knockout mouse; Male; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; NBTI-sensitive adenosine transporter; Nucleoside Transport Proteins; Protein Binding; Protein Precursors - biosynthesis; Protein Precursors - deficiency; Protein Precursors - genetics; Receptors, Purinergic P1 - genetics; Receptors, Purinergic P1 - metabolism; Thioinosine - analogs & derivatives; Thioinosine - pharmacology; Vertebrates: nervous system and sense organs; Xanthines - metabolism; Autoradiography; Enkephalin knockout; NBTI-sensitive adenosine transporter; Neurotransmitters, modulators, transporters and receptors; A 1 receptor; Knockout mouse; A 2A receptor; Adenosine; A2A receptor; Rodentia; Central nervous system; Enkephalin; Preproenkephalin; Neuropeptide; Opioid peptide; Encephalon; A1 receptor; Vertebrata; Mammalia; Mouse; Mutation; Adenosine receptor; Carrier protein; Biological receptor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.06.088

There is a large body of evidence indicating important interactions between the adenosine and the opioid systems in regulating pain, opioid dependence and withdrawal. Mice lacking the proenkephalin gene and therefore lacking the endogenous enkephalin peptides have been successfully developed and exhibit decreased locomotor activity, are hyperalgesic and show enhanced anxiety and aggression. In addition, an upregulation of μ and δ receptors was also observed in the brains of knockout mice. To investigate if there are any compensatory alterations in adenosine systems in the brains of mutant mice, we have carried out quantitative autoradiographic mapping of A 1 and A 2A adenosine receptors and nitrobenzylthioinosine (NBTI)-sensitive adenosine transporters in the brains of wild-type and homozygous enkephalin knockout mice. Adjacent coronal brain sections were cut from brains of +/+ and −/− mice for the determination of binding of [ 3H]1,3-dipropyl-8-cyclopentylxanthine ([ 3H]DPCPX), [ 3H]2-[ p-(2-carbonylethyl)phenylethylamino]-5′- N-ethylcarboxamidoadenosine ([ 3H]CGS21680) or [ 3H]NBTI to A 1 and A 2A adenosine receptors and NBTI-sensitive adenosine transporters, respectively. A small but significant increase in [ 3H]DPCPX and [ 3H]NBTI binding but no significant change in [ 3H]CGS21680 binding was detected in enkephalin knockout brains. The results provide further evidence of functional interactions in the brain between opioid receptors and A 1 adenosine receptors as well as NBTI-sensitive adenosine transporters but not A 2A receptors.