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

Abstract

SUMMARY1. The effects of noradrenaline on guinea-pig gall-bladder ganglia were investigated with intracellular recording techniques.2. Noradrenaline (0-01-100 /M) 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 /IM) caused an inhibition ranging from 93-100 %. The noradrenaline concentration that resulted in halfmaximal inhibition (EC50) of the EPSP was 280 nm.3. Experiments with selective agonists and antagonists indicated that the 2-adrenoreceptor was involved in the inhibition of the EPSP. Clonidine (0-001-100 /tM) 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 14 nM.4. Release of endogenous catecholamines by tyramine (100 /tM) in the presence of desipramine (10 1AM), 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 AM) 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 oc2-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.

The gall of subordination: changes in gall bladder function associated with social stress

“…Norepinephrine and opioids inhibit CCK-induced gall bladder contraction presynaptically (e.g. binding to α 2 -adrenergic or opioid receptors, respectively) at the interface between vagal nerve terminals and gall bladder neurons or smooth muscle (Mawe 1993;Guarraci et al 2002). Extended to our data on convict cichlids, these possible mechanisms imply a critical role for sympathetic modulation of gall bladder function in fishes exposed to chronic subordination.…”

“…cerebral injection of CRF) indicate an indirect role for CRF in the inhibition of gall bladder emptying. CRF, an important trigger for both peripheral and central stress axis activity, may enhance bile retention through its stimulatory effect on norepinephrine and opioid production (Lenz et al 1992(Lenz et al , 1993Mawe 1993Mawe , 1998Guarraci et al 2002). Norepinephrine and opioids inhibit CCK-induced gall bladder contraction presynaptically (e.g.…”

Chemical coding of intrinsic and extrinsic nerves in the guinea pig gallbladder: Distributions of PACAP and orphanin FQ

“…These results indicate that sympathetic nerves that innervate blood vessels in the gallbladder contain OFQ as well as norepinephrine and NPY. When activated, the sympathetic nerve fibers that are found in abundance in gallbladder ganglia can cause a presynaptic inhibition of neurotransmitter release from vagal preganglionic nerve terminals (Mawe, 1993;Mawe et al, 1994). Application of norepinephrine, pharmacological release of catecholamines from endogenous stores, and stimulation of sympathetic nerves suppress fast EPSPs in gallbladder ganglia.…”

Tachykinins as mediators of slow EPSPs in guinea‐pig gall‐bladder ganglia: involvement of neurokinin‐3 receptors.

“…It is likely that the increase in excitability involves a decrease in one or more potassium conductances. The late phase of the AHP, which lasts about 170 ms in guinea-pig gall-bladder neurones, is a Ca2+-dependent K+ event, and is sensitive to apamin (Mawe, 1990 Mawe, 1991Mawe, , 1993 suppression of the K+ conductance responsible for the late phase of the AHP, but inhibition of other K+ currents such as the A current is likely to contribute to the increase in excitability. Since tachykinins appear to be present in sensory fibres within gall-bladder ganglia, and since exogenous tachykinins activate gall-bladder neurones, an important issue to address is whether endogenous tachykinins can be released from these fibres and act within gall-bladder ganglia.…”

“…10). The other compounds that have been tested, CCK and noradrenaline, act presynaptically on vagus nerve terminals in these ganglia (Mawe, 1991(Mawe, , 1993Mawe, Gokin & Wells, 1994;see Fig. 10).…”