Noradrenaline release

Pittalnga A, Pattarini R, Severi P, Raiteri M (1996) Hnman brain N-methyl-D-aspartate receptors regnlating noradrenaline release are positively modnlated by HIV-1 coat protein gpl20. Aids 10(5) 463 68... 

Figure 2.4 Noradrenergic inhibition of Ca " currents and transmitter release in sympathetic neurons and their processes, (a) Inhibition of currents through N-type Ca " channels by external application of noradrenaline (NA) or by over-expression of G-protein P y2 subunits, recorded from the soma and dendrite of a dissociated rat superior cervical sympathetic neuron. Currents were evoked by two successive 10 ms steps from —70 mV to OmV, separated by a prepulse to -1-90 mV. Note that the transient inhibition produced by NA (mediated by the G-protein Go) and the tonic inhibition produced by the G-protein Piy2 subunits were temporarily reversed by the -1-90 mV depolarisation. (Adapted from Fig. 4 in Delmas, P et al. (2000) Nat. Neurosci. 3 670-678. Reproduced with permission), (b) Inhibition of noradrenaline release from neurites of rat superior cervical sympathetic neurons by the 2-adrenoceptor stimulant UK-14,304, recorded amperometrically. Note that pretreatment with Pertussis toxin (PTX), which prevents coupling of the adrenoceptor to Gq, abolished inhibition. (Adapted from Fig. 3 in Koh, D-S and Hille, B (1997) Proc. Natl. Acad. Sci. USA 1506-1511. Reproduced with permission)...

Many early studies of transmitter release depended on measuring its concentration in the effluent of a stimulated, perfused nerve/end-organ preparation. This technique is still widely used to study drug-induced changes in noradrenaline release from sympathetic neurons and the adrenal medulla. However, it is important to realise that the concentration of transmitter will represent only that proportion of transmitter which escapes into the perfusate ( overflow ) (Fig. 4.2). Monoamines, for instance, are rapidly sequestered by uptake into neuronal and non-neuronal tissue whereas other transmitters, such as acetylcholine, are metabolised extensively within the synapse. Because of these local clearance mechanisms, the amount of transmitter which overflows into the perfusate will depend not only on the frequency of nerve stimulation (i.e. release rate) but also on the dimensions of the synaptic cleft and the density of innervation. 

Pali), P and Stamford, JA (1993) Real-time monitoring of endogenous noradrenaline release in rat brain slices using fast cyclic voltammetry. 2. Operational characteristics of the alpha2 autoreceptors in the bed nucleus of the stria terminalis, pars ventralis. Brain Res. 608 134-140. 

While the amount of noradrenaline released from the terminals can be increased by nerve stimulation, it can be increased much more by drugs, like phenoxybenzamine, which block presynaptic a-adrenoceptors. These receptors are normally activated by increased noradrenaline in the synapse and trigger a feedback cascade, mediated by... 

Noradrenaline release might also be modulated by receptors on noradrenergic nerve terminals that are activated by other neurotransmitters ( heteroceptors ). Unfortunately, most studies of this type of modulation have been carried out in tissue slices and... 

Murugaiah, KD and O Donnell, JM (1995) Facilitation of noradrenaline release from rat brain slices by beta-adrenoceptors. Naunyn-Schmiedebergs Arch. Pharmacol. 351 483--490. 

Measurements of noradrenaline release in animals have not helped to resolve this confusion. Microdialysis studies in vivo have confirmed that anxiogenic doses of... 

Figure 22.3 Possible links in the induction of circadian rhythm between daylight, the suprachiasmatic nucleus and melatonin release from the pineal gland. Some fibres in the optic nerve, projecting from the eye to the lateral geniculate nucleus (LGN) in the thalamus, innervate the suprachiasmatic nucleus (SCN) in the anterior hypothalamus, via the retinohypothalamic tract (RHT). Others project to the SCN from the LGN in the geniculohypothalamic tract (GHT). The release of melatonin into the circulation from the pineal gland (PG) is maximal at night and appears to be controlled partly by noradrenaline released from sympathetic nerves originating in the superior cervical ganglion (SCG). Melatonin receptors are found in the SCN, the removal of which dampens melatonin secretion...

Haddock, P.S., Hearse, D.J. and Woodward, B. (1989). Effect of anti-oxidants and verapamil on noradrenaline release and contracture in the ischaemic/reperfused rat heart. Br. J. Pharmacol. 78, 745 (abstract). 

Schlicker, E., Fink, K., Hinterthaner, M. 8r Gothert, M. (1989). Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors. Naunyn Schmiedehergs Arch. Pharmacol. 340, 633-8. 

Timm, J., Marr, I., Werthwein, S. et al. (1998). H2 receptor-mediated facilitation and H3 receptor-mediated inhibition of noradrenaline release in the guinea-pig brain. Naunyn Schtniedebergs Arch. Pharmacol 357, 232-9. 

Hirst The neuronal response isn t changed by a blockade. We do get a neuronal response, which is purinergic. This suggested that any noradrenaline released reaches the smooth muscle in such a low concentration that it is without effect. 

Kehr J, Yoshitake T, Wang FH, Wynick D, Holmberg K, et al. 2001. Microdialysis in freely moving mice Determination of acetylcholine, serotonin and noradrenaline release in galanin transgenic mice. J Neuro Sci Method 109 71-80. 

L Heureux R, Dennis T, Curet O, Scatton B. 1986. Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis effects of drugs affecting noradrenergic transmission. J Neurochem 46(6) 1794-1801. 

Mateo Y, Pineda J, Meana JJ. 1998. Somatodendritic alpha2-adrenoceptors in the locus coeruleus are involved in the in vivo modulation of cortical noradrenaline release by the antidepressant desipramine. J Neurochem 71(2) 790-798. 

In ex vivo studies in which transmitter release is measured in synaptosome or slice preparations from animals treated with nicotine in vivo, no change (Grilli et al. 2005), decreased (Grady et al. 1997) and increased (Yu and Wecker 1994) striatal [ HJdopamine release has been reported. A similar picture has been observed for nAChR-evoked hippocampal [ H]noradrenaline release, with unchanged (Barik and Wonnacott 2006), decreased (Grilli et al. 2005) and increased (Jacobs et al. 2002) responses. As tissue is extensively washed prior to nAChR stimulation, these discrepancies are unlikely to reflect differences in nAChR desensitisation due... 

With respect to in vivo noradrenaline release, several studies report increases in response to nicotine challenge after chronic administration, consistent with a sensitised response. Sharp and co-workers demonstrated that rats self-administering nicotine in an unlimited access paradigm exhibited markedly increased levels of endogenous noradrenaline in the hypothalamic paraventricular nucleus (Fu et al. 2001) and amygdala (Fu et al. 2003). Also, in rats that received a daily nicotine injection (0.4mgkg ) for 5 days, noradrenaline release in the ventral hippocampus was enhanced in response to a subsequent nicotine challenge (Benwell and Balfour 1997). 

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