Potentiation of formalin-evoked adenosine release by an adenosine kinase inhibitor and an adenosine deaminase inhibitor in the rat hind paw: a microdialysis study

The present study examined the effects of local subcutaneous administration of formalin on adenosine release from the rat hind paw, and the effects of inhibitors of adenosine metabolism on such release. Microdialysis probes were inserted into the subcutaneous tissue of the plantar surface of rat hin...

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Bibliographic Details
Published in:European journal of pharmacology 2000-11, Vol.408 (2), p.143-152
Main Authors: Liu, Xue Jun, White, Thomas D, Sawynok, Jana
Format: Article
Language:English
Subjects:
Adenosine
Adenosine - metabolism
Adenosine deaminase
Adenosine Deaminase - metabolism
Adenosine Deaminase Inhibitors
Adenosine kinase
Adenosine Kinase - antagonists & inhibitors
Adenosine Kinase - metabolism
Animals
Biological and medical sciences
Deoxyadenosines - pharmacology
Fixatives - pharmacology
Formaldehyde - pharmacology
Formalin
Fundamental and applied biological sciences. Psychology
Hindlimb - drug effects
Hindlimb - metabolism
Inflammation
Male
Microdialysis
Microdialysis - methods
Molecular and cellular biology
Pain
Pain Measurement - drug effects
Pentostatin - pharmacology
Rats
Rats, Sprague-Dawley
Somesthesis and somesthetic pathways (proprioception, exteroception, nociception)
interoception
electrolocation. Sensory receptors
Vertebrates: nervous system and sense organs
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Summary:The present study examined the effects of local subcutaneous administration of formalin on adenosine release from the rat hind paw, and the effects of inhibitors of adenosine metabolism on such release. Microdialysis probes were inserted into the subcutaneous tissue of the plantar surface of rat hind paws. Samples were collected every 10 min at a perfusion rate of 2 μl/min and high performance liquid chromatography was used to measure adenosine levels. At lower concentrations of formalin (0.5–2.5%), a significant increase in adenosine levels was observed in the first 10 min after formalin injection, while at the highest concentration of formalin (5%), the increase in adenosine release was observed over 60 min. Co-administration of the adenosine kinase inhibitor 5′-amino-5′-deoxyadenosine (100 nmol) with formalin, significantly increased adenosine release evoked by 0.5–1.5% formalin, but did not produce a further enhancement of release evoked by 5% formalin. The adenosine deaminase inhibitor 2′-deoxycoformycin (100 nmol) significantly increased adenosine levels at 5% formalin but had no effect at lower concentrations of formalin. In confirmation of previous studies, subcutaneous injection of formalin (0.5–5%) produced a characteristic biphasic concentration-related expression of nociceptive behaviours and an increase in paw volume. This study directly demonstrates that formalin can evoke a concentration-dependent local release of adenosine from the rat hind paw. The ability of an adenosine kinase inhibitor and an adenosine deaminase inhibitor to modulate this release is dependent on substrate adenosine concentrations.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(00)00742-1