Protein kinase C-mediated suppression of the presynaptic adenosine A1 receptor by a facilitatory metabotropic glutamate receptor.
KCl-evoked glutamate exocytosis from cerebrocortical synaptosomes can be inhibited by the adenosine A1 receptor agonist cyclohexyladenosine (CHA). Inhibition is associated with a decreased KCl-evoked Ca2+ level elevation, and the effect of the agonist is occluded by prior incubation with the Agelenopsis aperta neurotoxin omega-agatoxin-IVA at 250 nM. The inhibition is suppressed in the presence of 3 nM phorbol dibutyrate (PDBu) or by activation of the protein kinase C (PKC)-coupled metabotropic glutamate receptor by 100 microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)ACPD]. A tonic inhibition of release by leaked exogenous adenosine can be reversed by adenosine deaminase or by PDBu addition. The CHA-induced inhibition can be enhanced by the PKC inhibitor Ro 31-8220. The mechanism for the suppression of the adenosine A1 receptor-mediated inhibition is distinct from that previously described for the (1S,3R)ACPD-evoked, PKC-mediated, facilitatory pathway, which enhances phosphorylation of the MARCKS protein, 4-aminopyridine-induced action potentials, and release of glutamate because the latter requires at least 100 nM PDBu [or the combination of (1S,3R)ACPD and arachidonic acid] and is not seen following KCl depolarization. Both PKC-mediated pathways may be involved in the presynaptic events associated with the establishment of synaptic plasticity.
Budd
D C
DC
Department of Biochemistry, University of Dundee, Scotland.
Nicholls
D G
DG
D000241:Adenosine / Q000819:agonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D017729:Presynaptic Terminals / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D058915:Purinergic P1 Receptor Antagonists; D018094:Receptors, Metabotropic Glutamate; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D018698:Glutamic Acid; D011493:Protein Kinase C; D000241:Adenosine