Nucleus tractus solitarius

In the gastrointestinal tract, drugs or toxins, as well as mechanical stimulation, induce emesis by activation of sensory receptors on afferent neurons in the vagus and sympathetic nerves. Information is relayed to the vomiting centre via the nucleus tractus solitarius... 

Substance P is a member of a group of polypeptides known as neurokinins or tachykinins. It is thought to be the primary neurotransmitter for the transfer of sensory information from the periphery to the spinal cord and brain. Substance P as well as neurokinin NKX receptors has been detected in vagal afferent neurons in the area postrema, nucleus tractus solitarius and dorsal motor nucleus of the vagus. Substance P has been shown to increase the firing rate of neurons in the area postrema and nucleus tractus solitarius and to produce retching when applied directly to these areas in animal studies. 

Hoskin, K. L., Lambert, G. A., Donaldson, C. and Zagami, A. S. The 5-hydroxytryptamine1B/iD/iF receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat. Brain Res. 998 91-99, 2004. 

FIGURE 1 8-5 Tissue-specific processing of the pro-opiomelanocortin (POMC) precursor yields a wide array of bioactive peptide products. Processing of the POMC precursor varies in various tissues. In anterior pituitary, adrenocorticotropic hormone (ACTH (1-39)) and P-1 ipo tropin (P-LPH) are the primary products of post-translational processing. Arcuate neurons produce the potent opiate P-endorphin (P-endo (1-31)) as well as ACTIK1 -13) NIT,. Intermediate pituitary produces a-melanocyte-stimulating hormone (aMSH), acetylated P endof 1 31) and P-endo(l-27). NTS, nucleus tractus solitarius. 

Williams CL, Men D, Clayton EC. 2000. The effects of noradrenergic activation of the nucleus tractus solitarius on memory and in potentiating norepinephrine release in the amygdala. Behav Neurosci 114(6) 1131-1144. 

Figure 6.5. Distribution of the 5-HT3 receptor. The 5-HT3 receptor subtype is a ligand gated ion channel that controls dopamine release. It is a common target of antiemetic therapy, as well as other psychoactive drugs. A high density of 5-HT3 receptors has been identified in the human brainstem, particularly in the area postrema (the putatitive vomiting centre of the brain) and the nucleus tractus solitarius. Lower levels of expression of the 5-HT3 receptor have been shown in the limbic system, hippocampus...

These brain-stem regions are interrelated by diverse neuronal projections and are connected to adrenergic structures [Dampney et al. 1977 Marovitch et al. 1982], such as the locus coeruleus, which are postulated to play a role in panic attacks [Gorman et al. 1989]. Further, experimental evidence suggests that CCK interacts with these brain stem mechanisms in modulating respiratory and cardiovascular functions. Microiontophoretic application of CCK-8S to neurons of the nucleus tractus solitarius in cats decreased both neuronal firing and respiratory frequency, effects that were reversed by administration of CCK-4 [Denavit-Saubie et al. 1985]. 

Denavit-Saubie M, Hurle MA, Morin-Surun MP, et al The effects of cholecystokinin-8 in the nucleus tractus solitarius, in Neuronal Cholecystokinin. Edited by Vanderhaeghen JJ, Crawley JN. New York, New York Academy of Sciences, 1985, pp 375-384... 

Most of the haemodynamic effects of opioids are related to decreased central sympathetic outflow, specific vagal effects or, in the case of morphine and pethidine, histamine release. Fentanyl and its analogues do not cause histamine release. All opioids, with the exception of pethidine, produce bradycardia by actions on the afferent fibres of the vagus and the nucleus tractus solitarius and nucleus commissuralis, which have very high densities of opioid receptors. Pethidine often produces tachycardia, possibly due to its structural similarity to atropine. In isolated heart or heart-muscle preparations, opioids produce a dose-related negative inotropic effect, but only at concentrations 100 to several thousand times those found clinically. 

Dopamine receptors are found in high concentration in the area postrema, which contains the chemoreceptor trigger zone (CTZ). Histamine Hl-receptors are concentrated in the nucleus tractus solitarius, which processes information relating to emesis, and in the dorsal motor nucleus of the vagus. This nucleus and the nucleus ambiguus also contain muscarinic cholinergic receptors, and these initiate motor components of vomiting. 

Substance P (SP) is a member of the family of tachykinin peptides that also includes neurokinin A and B. Their respective receptors are tachykinin NKl, tachykinin NK2 and tachykinin NK3. Substance P is best known as a pain neurotransmitter, but it also controls vomiting. In relation to emesis, its sites of localisation include the area postrema and the nucleus tractus solitarius. 

Endoh T. (2004). Characterization of modulatory effects of postsynaptic metabotropic glutamate receptors on calcium currents in rat nucleus tractus solitarius. Brain Res. 1024 212-224. 

However, activation of the central nervous system (CNS) does not equate with EEG arousals or awakenings. CNS activation implies that integrative neurons were activated and sent information to descending pathways, the nucleus tractus solitarius, and sympathetic controlling cells. An ANS modulation is always associated with an efferent response. CNS activation may lead to an arousal, an awakening, or an important ANS activity change, but activation may be limited to a polysynaptic reflex response with ANS change and no EEG arousal (6). 

The brainstem vomiting center is located in the lateral medullary reticular formation and coordinates the complex act of vomiting through interactions with cranial nerves VIII and X and neural networks in the nucleus tractus solitarius that control respiratory, salivatory, and vasomotor centers. High concentrations of muscarinic, histamine Hi, and serotonin 5-HT3 receptors have been identified in the vomiting center. 

Barraco RA, Clough-Helfman C, Goodwin BP et al (1995) Evidence for presynaptic adenosine A2a receptors associated with norepinephrine release and their desensitization in the rat nucleus tractus solitarius. J Neurochem 65 1604-11... 

Barraco RA, Helfman CC, Anderson GF (1996) Augmented release of serotonin by adenosine A2a receptor activation and desensitization by CGS 21680 in the rat nucleus tractus solitarius. Brain Res 733 155-61... 

Helfman CC, Zhong H, Barraco RA et al (1996) The effects of 5 -N-ethylcarboxamidoadenosine on evoked release of [3H]serotonin in the rat nucleus tractus solitarius. Neurosci Lett 213 61-5 Hertting G, Wurster S, Allgaier C (1990) Regulatory proteins in presynaptic function. Ann N Y Acad Sd 604 289-304... 

Smith BN, Davis SF, van den Pol AN et al (2002) Selective enhancement of excitatory synaptic activity in the rat nucleus tractus solitarius by hypocretin 2. Neuroscience 115 707-14 Smith-White MA, Herzog H, Potter EK (2002) Role of neuropeptide Y Y2 receptors in modulation of cardiac parasympathetic neurotransmission. Regul Peptides 103 105-11 Stanford IM, Cooper Al (1999) Presynaptic mu and delta opioid receptor modulation of GABAa IPSCs in the rat globus pallidus in vitro. 1 Neurosci 19 4796 4803 Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77 1-124... 

Doyle MW, Bailey TW, Jin Y-H, Andresen MC (2002) VaniUoid receptors presynaptically modulate cranial visceral afferent synaptic transmission in nucleus tractus solitarius. J Neurosci 22 8222-9... 

Ashworth-Preece MA, Jarrott B, Lawrence AJ. 5-Hydroxytiyptamine3 receptor modulation of excitatory amino acid release in the rat nucleus tractus solitarius. NeurosciLett 1995 191 75-78. 

Pratt GD, Bowery NG. The 5-HT3 receptor ligand, [3H]BRL 43694, binds to presynaptic sites in the nucleus tractus solitarius of the rat. Neuropharmacology... 

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