Increases in interstitial adenosine and cerebral blood flow with inhibition of adenosine kinase and adenosine deaminase
| Autor: | Veronica M. Sciotti, David G. L. Van Wylen |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
medicine.medical_specialty animal structures Adenosine Adenosine kinase Adenosine receptor antagonist Tubercidin Adenosine A1 receptor Internal medicine Dialysis Solutions medicine Adenosine Deaminase Inhibitors Animals heterocyclic compounds Rats Wistar Adenosine Kinase Hypoxanthine biology Dose-Response Relationship Drug Chemistry Adenine Brain Adenosine A3 receptor Adenosine receptor Inosine Rats Endocrinology Neurology Cerebrovascular Circulation Hypoxanthines biology.protein Neurology (clinical) EHNA Cardiology and Cardiovascular Medicine Adenosine Deaminase Inhibitor Extracellular Space medicine.drug |
| Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 13(2) |
| ISSN: | 0271-678X |
| Popis: | The purpose of this study was to determine the changes in interstitial fluid (ISF) adenosine and cerebral blood flow (CBF) during inhibition of adenosine kinase or adenosine deaminase. Brain microdialysis was used to (a) measure CBF (H2 clearance), (b) sample cerebral ISF, and (c) deliver drugs locally to the brain. Microdialysis probes were implanted bilaterally in the caudate nucleus of halothane-anesthetized rats ( n = 11). One probe was perfused with artificial cerebrospinal fluid (CSF) containing iodotubercidin (IODO), an adenosine kinase inhibitor, while the other probe was perfused with erythro-2-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor. Both probes were subsequently perfused with EHNA + IODO. Finally, 8-( p-sulfophenyl)theophylline (SPT), an adenosine receptor antagonist, was added to EHNA + IODO in one probe, while the other probe continued to receive only EHNA + IODO. CBF and dialysate adenosine levels increased with either EHNA or IODO; however, the increases were greater with IODO. EHNA + IODO further increased CBF and dialysate adenosine. The hyperemia observed with EHNA + IODO was abolished by adenosine receptor blockade. These data suggest that basal adenosine levels are influenced to a greater extent by adenosine kinase than by adenosine deaminase. In addition, the increased CBF observed with inhibition of adenosine metabolism and the attenuation of this vasodilatory response with adenosine receptor blockade support a role for adenosine in CBF regulation. |
| Databáze: | OpenAIRE |
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