Adenosine A1 receptor inhibition of glutamate exocytosis and protein kinase C-mediated decoupling.
The adenosine modulation of glutamate exocytosis from guinea pig cerebrocortical synaptosomes is investigated. Endogenously leaked adenosine is sufficient to cause a partial tonic inhibition of 4-aminopyridine-evoked glutamate release, which can be relieved by adenosine deaminase. The adenosine A1 receptor is equally effective in mediating inhibition of glutamate exocytosis evoked by 4-aminopyridine (where K(+)-channel activation would inhibit release) and by elevated KCl (where K(+)-channel activation would have no effect), arguing for a central role of Ca(2+)-channel modulation. In support of this, the plateau phase of depolarization-evoked free Ca2+ elevation is decreased by adenosine with both depolarization protocols. No effect of adenosine agonists is seen on membrane potential in polarized or KCl- or 4-aminopyridine-stimulated synaptosomes. The interaction of protein kinase C with the A1 receptor-mediated inhibition is examined. Activation of protein kinase C by 4 beta-phorbol dibutyrate has been shown previously by this laboratory to modulate glutamate release via K(+)-channel inhibition, and is shown here to have an additional action of decoupling the adenosine inhibition of glutamate exocytosis.
Barrie
A P
AP
Department of Biochemistry, University of Dundee, Scotland.
Nicholls
D G
DG
D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004789:Enzyme Activation; D005089:Exocytosis; D016257:Fura-2; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006168:Guinea Pigs; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D005971:Glutamates; D011983:Receptors, Purinergic; C053907:8-cyclopentyl-1,3-dimethylxanthine; C027513:N(6)-cyclohexyladenosine; D018698:Glutamic Acid; D011189:Potassium Chloride; D015761:4-Aminopyridine; D013806:Theophylline; D011493:Protein Kinase C; D000241:Adenosine; D016257:Fura-2