Noradrenaline modulation

It is concluded that noradrenaline modulates cooperation and other socially adaptive behaviours and this action may promote friendship formation and facilitate social support. 

Benham, C.D. and Tsien, R.W. (1988) Noradrenaline modulation of calcium channels in single smooth muscle cells from rabbit ear artery. Journal of Physiology, 404 767-784. 

In 1966, the name was proposed (5) for receptors blocked by the at that time known antihistamines. It was also speculated that the other actions of histamine were likely to be mediated by other histamine receptors. The existence of the H2 receptor was accepted in 1972 (6) and the receptor was recognized in rat brain in 1983 (7). receptors in the brain appear to be involved in the feedback control of both histamine synthesis and release, whereas release of various other neurotransmitters, eg, serotinin (5-HT), dopamine, noradrenaline, and acetylcholine, is also modulated (8) (see Neuroregulators). 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Even more sophisticated control of neurotransmitter release is suggested by the possibility of heteroceptors . These receptors are thought to be located on the terminals of, and to modulate transmitter release from, one type of neuron, but are activated by transmitter released from a different type of neuron (Laduron 1985). For example, noradrenaline has been proposed to modulate release of a wide range of transmitters (e.g. dopamine, 5-HT and glutamate) through activation of a2-heteroceptors on the terminals of each of these different types of neuron. However, one factor that should be borne in mind is that most of the evidence for heteroceptors comes from studies of... 

Evidence suggests that co-transmitters in a terminal have their own autoreceptors and, in some cases, activation of their own presynaptic receptor can influence the release of the co-stored, classical transmitter. For instance, activation of P2Y-autoreceptors by ATP is thought to affect the release of noradrenaline from sympathetic neurons. However, in other cases, feedback modulation of release of classical and their associated co-transmitters seems to have separate control mechanisms. This would suggest that either the two types of transmitter are concentrated in different nerve terminals or that mechanisms for regulating release target different vesicles located in different zones of the terminal (Burnstock 1990). 

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... 

Dailey, JW, Mason, K and Stanford, SC (1996) Increased levels of extracellular noradrenaline in the frontal cortex of rats exposed to naturalistic environmental stimuli modulation by acute systemic administration of diazepam or buspirone. Psychopharmacology 127 47-54. 

Finally, as outlined above, descending monoamine systems, originating in the midbrain and brainstem that act through the spinal release of noradrenaline and 5-HT, modulate the spinal transmission of pain. Alphai adrenoceptors appear to be important in this role but it is unlikely that behavioural effects such as sedation can be separated from the analgesia. Since both noradrenaline and 5-HT are key transmitters in the control of mood and anxiety and yet also participate in the control of sensory events that lead to... 

Cape EG and Jones, BE (1998) Differential modulation of high-frequency gamma-electroencephalogram activity and sleep-wake state by noradrenaline and serotonin microinjections into the region of cholinergic basalis neurons. J. Neurosci. 18 2653-2666. 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

In transfected cells, H3 receptor mediated activation of Gj/0 proteins has also been reported to modulate arachi-donic acid release [29] and the Na+/H+ exchanger [44], and to inhibit Ca2+ influx and exocytosis of [3H] noradrenaline from transfected SH-SY5Y-H3 cells [45], The inhibition of Ca2+ influx may be particularly relevant in view of the known physiological function of the brain H3 receptor. 

Porter VA, Bonev AD, Knot HJ et al 1998 Frequency modulation of Ca2+ sparks is involved in regulation of arterial diameter by cyclic nucleotides. Am J Physiol 274 C1346—C1355 Pucovsky V, Gordienko D V, Bolton TB 2002 Effect of nitric oxide donors and noradrenaline on Ca2+ release sites and global intracellular Ca2+ in myocytes from guinea-pig small mesenteric arteries. J Physiol 539 25—39... 

Hirst That is an example. There is no doubt that some transmitters get to arterioles, but it is equally not clear to me that in a mesenteric arteriole noradrenaline accesses the a receptors. ATP might access purine receptors and trigger voltage-dependent Ca2+ entry, but we have been told that CICR doesn t necessarily occur there. It is not clear that this pathway is used. It is, however, used to modulate depolarization. 

The diagram below shows the pathway of pain transmission from the peripheral nerves to the cerebral cortex. There are three levels of neuronal involvement and the signals may be modulated at two points during their course to the cerebral cortex. Descending inhibitory pathways arise in the midbrain and pass to the dorsal horn as shown. Multiple different neurotransmitters are involved in the pathway and include gamma-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), noradrenaline and opioids. 

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. 

Balfour DJ (2002) Neuroplasticity within the mesoaccumbens dopamine system and its role in tobacco Dependence, Curr Drug Targets CNS Neurol Disord 1 413-21 Balfour DJ (2004) The neurobiology of tobacco dependence a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 6 899-912 Barik J, Wonnacott S (2006) Indirect modulation by alpha7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices interaction with glutamate and GABA systems and effect of nicotine withdrawal. Mol Pharmacol 69 618-628... 

Rump CL, Bohmann C, Schaible U, Schollhorn J, Limberger N (1995) ajc-Adrenoceptor-modulated release of noradrenaline in human right atrium. Br J Pharmacol 116 2617-2624... 

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