Adenosine-elicited accumulation of cyclic AMP in brain slices: Potentiation by agents which inhibit uptake of adenosine
| Autor: | Minta Huang, John W. Daly |
|---|---|
| Rok vydání: | 1974 |
| Předmět: |
Male
medicine.medical_specialty Adenosine Guinea Pigs Guanosine Benzoates General Biochemistry Genetics and Molecular Biology Tubercidin Norepinephrine Structure-Activity Relationship Adenosine A1 receptor chemistry.chemical_compound Theophylline Papaverine Internal medicine Cyclic AMP medicine Animals Carbon Radioisotopes Hexobendine General Pharmacology Toxicology and Pharmaceutics Cerebral Cortex Deoxyadenosines Chemistry Phosphodiesterase Biological Transport Drug Synergism Dipyridamole Purine Nucleosides General Medicine Ethylenediamines Adenosine receptor Endocrinology Bucladesine Xanthines Histamine medicine.drug |
| Zdroj: | Life Sciences. 14:489-503 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/0024-3205(74)90364-6 |
| Popis: | The uptake and incorporation of low concentrations of radioactive adenosine into guinea pig cerebral cortical slices is effectively inhibited by dipyridamole, hexobendine, papaverine, 6-( p -nitrobenzylthio) guanosine, 5′-deoxy-adenosine and N6-phenyladenosine and ineffectively inhibited by other adenosine analogs such as 2-chloroadenosine, 3′-deoxyadenosine and tubercidin or by phosphodiesterase inhibitors such as theophylline, isobutylmethylxanthine, and N, 0-dibutyrylcyclic AMP. When uptake of 10–20 adenosine is inhibited 50–70% by dipyridamole, hexobendine, papaverine or 6-( p -nitrobenzylthio)-guanosine, the adenosine-elicited accumulation of cyclic AMP is potentiated 2–3 fold. Potentiation of the effects of low concentrations of adenosine by various agents parallels more closely their efficacy as inhibitors of adenosine uptake rather than their potency as phosphodiesterase inhibitors. Amine-elicited accumulations of cyclic AMP are enhanced by hexobendine, dipyridamole, papaverine and 6-( p -nitrobenzylthio) guanosine and this enhancement is blocked by an adenosine antagonist, theophylline. The stimulatory effects of the adenosine analogs, 5′-deoxyadenosine, 2-chloroadenosine and N6-phenyladenosine are blocked by theophylline and potentiated by hexobendine. The results are compatible with the hypothesis that the specific inhibition of uptake of adenosine potentiates adenosine or amine-elicited accumulations of cyclic AMP by increasing the effective extracellular concentration of adenosine within the slice. The inhibition or stimulation of cyclic AMP accumulation by adenosine analogs is consonant with differential activities as agonist or antagonist at an extracellular adenosine receptor. |
| Databáze: | OpenAIRE |
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