The presynaptic site of action of norepinephrine in the superior cervical ganglion of guinea pig.

Supramaximal preganglionic volleys did not elicit detectable postsynaptic potential in the curare-treated superior cervical ganglion cell of the guinea pig whereas, a tetanic stimulation (10-30 Hz, 1-5 seconds) consistently evoked a monophasic depolarizing potential resembling the slow excitatory postsynaptic potential. The depolarizing potential was not preceded by a detectable hyperpolarization. In non-curare-treated preparations, norepinephrine in concentrations of 1 to 10 muM consistently and reversibly suppressed the fast excitatory postsynaptic potential elicited by submaximal preganglionic stimulation without appreciably affecting the resting membrane potential, the total membrane resistance or the cell membrane excitability. Pretreating the ganglion with phenoxybenzamine (10 muM) completely prevented, whereas propranolol (30 muM) failed to antagonize, the ganglionic depressant action of norepinephrine. The amplitude and time course of the iontophoretically induced acetylcholine potential were not significantly altered by norepinephrine in concentrations which markedly attenuated the response of the fast excitatory postsynaptic potential. The frequency but not the amplitude of the miniature excitatory postsynaptic potentials was significantly reduced by norepinephrine (1-10 muM). These results demonstrate that norepinephrine inhibits ganglionic transmission in the guinea pig principally by reducing the output of acetylcholine from the presynaptic nerve terminals. These data are discussed with respect to their relation to the presence in the guinea pig superior cervical ganglion of norepinephrine-containing small intensely fluorescent cells which are not connected synaptically with the postganglionic neurons.