ADENOSINE AZ RECEPTORS MEDIATE RETINOTECTAL PRESYNAPTIC INHIBITION - UNCOUPLING BY C-KINASE AND ROLE IN LTP DURING REGENERATION

Presynaptic adenosine receptors inhibit transmitter release at many sy napses and are known to exist on retinotectal terminals. In this paper we show that adenosine decreases retinotectal field potentials by sim ilar to 30% and investigate the mechanism. First, as judged by the eff ects of specific calcium channel blockers, retinotectal transmission w as mediated almost exclusively by N-type calcium channels, which are k nown to be modulated by adenosine A1 receptors. Transmission was compl etely blocked by either omega-Conotoxin GVIA (-100%, N-type blocker) o r omega-Conotoxin MVIIC (-99%, N-, P-and Q-type blocker) and was not s ignificantly affected by omega-Agatoxin IVA [+1.7 +/- 9.3% (SE), P-, Q -type blocker], but was augmented slightly by nifedipine (+9.3 +/- 2.1 %, L-type blocker). Second, the adenosine inhibition was presynaptic, as indicated by a 43% increase in paired-pulse facilitation. Third, th e selective A1 agonist cyclohexyl adenosine (CHA) at 50 nM caused a 21 % decrease in amplitude and the selective A2 agonist [2-(3,5-dimethoxy phenyl)-2-(2-methylphenyl)-ethyl] adenosine (DPMA) at 100 nM caused a 24% increase. Fourth, the selective A1 antagonist 8-cyclopentyl-1,3-di propylxanthine (DPCPX) alone produced an increase in the field potenti al, suggesting a tonic inhibition mediated by endogenous adenosine. Fi fth, pertussis toxin eliminated adenosine inhibition implicating G(i) or G(o) protein coupling. Sixth, C-kinase activation eliminated the A1 -mediated inhibition. In regenerating projections, adenosine also caus ed a decrease in transmission (-30 +/- 12%), but after induction of lo ng-term potentiation (LTP) via trains of stimuli or via treatment with the phosphatase inhibitor okadaic acid, the adenosine response was co nverted to an augmentation. Because LTP is associated with C-kinase ac tivation, this is consistent with C-kinase uncoupling the A1 receptor from inhibiting N-type Ca2+ channels. This uncovers the A2-mediated au gmentation as demonstrated in normals with DPMA. Such an effect could account in part for the LTP of immature synapses and the change from r apidly fatiguing to robust synaptic transmission.