Long-term potentiation of transmitter release induced by adrenaline in bull-frog sympathetic ganglia.

Long-term potentiation (l.t.p.) of transmitter release induced by adrenaline in bull-frog sympathetic ganglia was studied using intracellular recording techniques. The quantal content of the fast excitatory post-synaptic potentials (fast e.p.s.p.s: evoked by the nicotinic action of acetylcholine) was potentiated for more than several hours after treatment with adrenaline (1-100 microM). A similar l.t.p. of quantal content was produced consistently by isoprenaline (10 microM) and only in a certain fraction of cells by dopamine (10 microM). The l.t.p. induced by adrenaline (10 microM) was blocked by a beta-antagonist, propranolol (1 microM), but not by an alpha-antagonist, phenoxybenzamine (1 microM). Dibutyryl adenosine 3',5'-phosphate (dibutyryl cyclic AMP) (0.8-1.0 mM), adenosine 3',5'-phosphate (cyclic AMP) (4 mM), 3-isobutyl-1-methylxanthine (10 microM), caffeine (1-2 mM), and cholera toxin (2 micrograms ml-1) applied for 20-30 min, all caused the l.t.p. of quantal content. By contrast, adenosine 5'-phosphate (AMP) (4 mM) and adenosine (4 mM) had no potentiating action. Treatment of the ganglion with adrenaline (2.5-160 microM) or dibutyryl cyclic AMP (4 mM) for 15-30 min resulted in the l.t.p. of the frequency of miniature e.p.s.p.s. The l.t.p. of quantal content induced by adrenaline was markedly suppressed by lowering temperature from 20-25 degrees C to 11-13 degrees C, and blocked by dibutyryl guanosine 3',5'-phosphate (dibutyryl cyclic GMP) (100 microM) consistently when applied together, but inconsistently when given after adrenaline. The post-synaptic sensitivity to acetylcholine was unchanged for at least 1 h after exposure to adrenaline (2.5-160 microM) or dibutyryl cyclic AMP (0.8-4 mM). It can be concluded that adrenaline produces l.t.p. of transmitter release by activating a cyclic-AMP-dependent metabolic process through the activation of beta-adrenoceptors, and that this mechanism is presumably regulated by a process involving endogenous guanosine 3',5'-phosphate (cyclic GMP).