Adenosine A1 receptor activation inhibits LTP in sympathetic ganglia

Abstract

The effects of adenosine on long-term potentiation of sympathetic ganglia was studied in the isolated superior cervical ganglion of the rat, using extracellularly recorded compound action potential as an index of synaptic transmission. Adenosine in a small concentration (2 μM) blocked the post-tetanic potentiation without affecting long-term potentiation. Higher concentrations blocked both responses with no significant effect on basal transmission. The inhibitory effect appears to be due to activation of adenosine A1 receptors. This was indicated by results from experiments with the A1 agonist N 6-cyclopentyladenosine (1 μM) which caused inhibition of the basal transmission as well as long-term potentiation and post-tetanic potentiation. This inhibition was readily antagonized by 8-phenyltheophylline (1 μM), an A1 receptor antagonist. A small enhancement of basal transmission was seen on treatment with 8-phenyltheophylline. The inhibitory effect of N 6-cyclopentyladenosine on long-term potentiation was totally prevented when the Ca 2+ concentration in the superfusate was doubled (from 2.2 to 4.4 mM). The adenosine A2 receptor agonist 5′-( N-cyclopropyl)-carboxamidoadenosine (1 μM), although caused a slight potentiation of basal transmission, had no significant effect on the post-tetanic potentiation or long-term potentiation. The adenosine transport inhibitors, dipyridamole (2 μM) and S-(4-nitorobenzyl)-6-thioinosine (2 μM) caused significant inhibition of the basal ganglionic transmission without affecting post-tetanic potentiation or long-term potentiation. The effect of dipyradimole on basal transmission was not antagonized in the presence of 8-phenyltheophylline suggesting a non-specific action. The results suggest that exogenous adenosine can inhibit both post-tetanic potentiation and long-term potentiation in sympathetic ganglia, probably by activation of presynaptic A1 receptors. The results also suggest that endogenous adenosine, which is probably released in minute amounts, may only modulate basal transmission without influencing induction or maintenance of long-term potentiation in the superior cervical ganglion.