Noradrenaline as a presynaptic inhibitory neurotransmitter in ganglia of the guinea-pig gall-bladder.

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1. The effects of noradrenaline on guinea-pig gall-bladder ganglia were investigated with intracellular recording techniques. 2. Noradrenaline (0.01-100 microM) decreased the amplitude of the fast excitatory postsynaptic potential (EPSP) that was evoked by stimulation of interganglionic fibre tracts. High concentrations of noradrenaline (10-100 microM) caused an inhibition ranging from 93-100%. The noradrenaline concentration that resulted in half-maximal inhibition (EC50) of the EPSP was 280 nM. 3. Experiments with selective agonists and antagonists indicated that the alpha 2-adrenoreceptor was involved in the inhibition of the EPSP. Clonidine (0.001-100 microM) reduced the EPSP in a concentration-dependent manner with an EC50 of 30 nM. Yohimbine (100-300 nM) caused a rightward shift of the noradrenaline concentration-effect relationship, with a dissociation equilibrium constant of 1.4 nM. 4. Release of endogenous catecholamines by tyramine (100 microM) in the presence of desipramine (1.0 microM), caused a yohimbine-sensitive decrease in the amplitude of the EPSP. Treatment with tyramine did not affect the amplitude of the EPSP in tissue that had undergone prior chemical sympathectomy with 6-hydroxydopamine. 5. Electrical stimulation of the vascular plexus (1-3 s; 10-20 Hz; 10 mA) decreased the amplitude of the EPSP. In some cases suprathreshold responses were reduced to subthreshold EPSPs following stimulation of the vascular plexus. Yohimbine (300 nM) reversibly inhibited the effects of vascular plexus stimulation. 6. Noradrenaline did not modify the responses of gall-bladder neurones to exogenously applied acetylcholine. Also, application of noradrenaline, by superfusion (0.001-100 microM) or by pressure microejection (1.0 mM), had no effect on the resting membrane potential, membrane conductance, or action potential characteristics of gall-bladder neurones. 7. Immunoreactivity for type A monoamine oxidase (MAO-A) was found in the vascular plexus and the ganglionated plexus of the gall-bladder. 8. These results show that noradrenaline has an alpha 2-adrenoreceptor-mediated presynaptic inhibitory effect on fast synaptic transmission in the ganglia of the guinea-pig gall-bladder. It is proposed that vagal terminals may be an important target of this adrenergic inhibitory input to the gall-bladder.

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