The mechanism of the inhibitory action of adrenaline on transmitter release in bullfrog sympathetic ganglia: independence of cyclic AMP and calcium ions

Abstract

The effects of adrenaline and dibutyryl adenosine 3':5' - cyclic monophosphate (db cyclic AMP) on nicotinic transmission in bullfrog sympathetic ganglia were compared by use of an intracellular recording technique. The evoked release of transmitter, acetylcholine (ACh), was decreased in the presence of adrenaline (10-100 microM), while the postsynaptic sensitivity to ACh was unchanged (10 microM adrenaline) or slightly reduced (100 microM). Transmitter release was similarly inhibited by dopamine (10 microM), but not by isoprenaline (10 microM). The inhibitory action of adrenaline on transmitter release was blocked by phenoxybenzamine but not by propranolol. The inhibition of transmitter release was independent of the external calcium concentration. The evoked release of transmitter and the electrical properties of the postsynaptic membrane were unchanged during exposure to db cyclic AMP (1-4 mM), while the postsynaptic sensitivity to ACh was slightly but significantly depressed. The spontaneous release of transmitter in a high K+ (10 mM) solution was decreased in the presence of adrenaline (100-300 microM), but unchanged with db cyclic AMP (4 mM). In contrast to the effects during exposure, both the evoked and spontaneous release of transmitter were enhanced after the removal of adrenaline or db cyclic AMP. Neither adrenaline (100 microM) nor db cyclic AMP (4 mM) affected the presynaptic spike and synaptic delay. It is concluded that adrenaline mainly inhibits the release of ACh from the presynaptic terminals through its alpha-action, while db cyclic AMP reduces slightly the postsynaptic sensitivity to ACh and that both agents facilitate transmitter release when they are removed from the presynaptic terminals. It is further suggested that the inhibitory action of adrenaline is independent of endogenous cyclic AMP and calcium ions.