Neurotransmitters acetylcholine noradrenaline

Fig. 15. Hypothetical model of how initiators and modulators that affect insulin release may reach A-, B- and D-cells. The first target of arterial blood containing nutrients, hormones, peptides and drugs is the B-cell. From there, via an intraislet portal vein system, blood which now also contains released insulin flows to the mantle where A- and D-cells are localized and from there enters the circulation. Nerves derived from the autonomous nervous system which contain neurotransmitters (acetylcholine, noradrenaline) and neuropeptides (including vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), galanin) are connected to islet cells. Glucagon (A-cells) and somatostatin (D-cells) reach other endocrine cells in the islet in a paracrine manner. The B-cell may also be the target of previously released insulin via a short loop.

Some arousal-related neurotransmitters, including noradrenaline, serotonin, and acetylcholine, feed back to inhibit POA sleep-active neurons. This aspect of the system has been reviewed previously (McGinty Szymusiak, 2000 Saper et al., 2001). Therefore, once sleep-active neurons are activated, arousal-related neurons are inhibited, and inhibitory control of sleep-active neurons by arousal systems is reduced. In this way, sleep onset is facilitated. That is, the mutually inhibitory systems can switch more quickly from wake to sleep, and back. These mutually inhibitory interactions also promote stability of both waking and sleep. 

Type II neurotransmitters These are slow-acting neurotransmitters, including acetylcholine, noradrenaline, adrenaline, dopamine and 5-hydroxytryptamine (Figure 14.6). 

There is now evidence that the mammalian central nervous system contains several dozen neurotransmitters such as acetylcholine, noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), together with many more co-transmitters, which are mainly small peptides such as met-enkephalin and neuromodulators such as the prostaglandins. It is well established that any one nerve cell may be influenced by more than one of these transmitters at any time. If, for example, the inhibitory amino acids (GABA or glycine) activate a cell membrane then the activity of the membrane will be depressed, whereas if the excitatory amino acid glutamate activates the nerve membrane, activity will be increased. The final response of the nerve cell that receives all this information will thus depend on the balance between the various stimuli that impinge upon it. 

GABA is also present in very high concentrations in the mammalian brain, approximately 500 jUg/g wet weight of brain being recorded for some regions Thus GABA is present in a concentration some 200-1000 times greater than neurotransmitters such as acetylcholine, noradrenaline and 5-HT. 

Histochemically, Alzheimer s disease is associated with multiple deficits in various neurotransmitters or their associated markers such as acetylcholine, noradrenaline, somatostatin, and others. 

There are a large variety of messengers, many of them quite simple molecules. Neurotransmitters include such compounds as acetylcholine, noradrenaline, dopamine, y-aminobutanoic acid (GABA), serotonin, 5-hydroxytryptophan, and even glycine (Fig. 5.3). 

In the past, it has been assumed that only one type of neurotransmitter is released from any one type of nerve cell. This is now known not to be true. Certainly as far as the amine neurotransmitters (i.e. acetylcholine, noradrenaline, glycine, serotonin, GABA, and dopamine) are concerned, it is generally true that only one of these messengers is released by any one nerve cell. 

Small intestine cholinergic and adrenergic neurons Miftakhov and Wingate [1994a] used the ////equations (fast sodium current, delayed rectifier potassium current, and a leakage current attributed to chloride channels) and added a system of equations to model the release of the neurotransmitter acetylcholine by the presynaptic terminal. Similarly release of noradrenaline was modeled in Miftakhov and Wingate [1994b]. 

Many alkaloids have strong biological activities in man. In part this can be explained by structural relationship with important signal compounds (neurotransmitters) such as dopamine, acetylcholine, noradrenaline, and serotonin. The fact that alkaloids are water soluble under acidic conditions and lipid soluble under neutral and basic conditions give them unique properties for medicinal use, as they can be transported in the protonated form, and can pass membranes in the neutral form. In fact most synthetic medicines do contain one or more tertiary nitrogens. 

Many alkaloids act on the nervous system, one of two important information systems in animals. The nervous system transmits perceived environmental changes rapidly to a specific processing center. The fundamental unit involved in this change is the neuron, with the information being transferred across a minute gap (2 X 10 mm) called a synapse (Cordell, 1981). Although the information is passed electrically within the neuron, it is passed chemically between neurons by neurotransmitters. The four most commonly recognized neurotransmitters are acetylcholine, noradrenaline, dopamine, and serotonin. The reactive site for these chemicals on the adjacent neuron is called a receptor (Cordell, 1981). 

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). 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

The neural structures involved in the promotion of the waking (W) state are located in the (1) brainstem [dorsal raphe nucleus (DRN), median raphe nucleus (MRN), locus coeruleus (LC), laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), and medial-pontine reticular formation (mPRF)] (2) hypothalamus [tuberomammillary nucleus (TMN) and lateral hypothalamus (LH)[ (3) basal forebrain (BFB) (medial septal area, nucleus basalis of Meynert) and (4) midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (Pace-Schott Hobson, 2002 Jones, 2003). The following neurotransmitters function to promote W (1) acetylcholine (ACh LDT/PPT, BFB) (2) noradrenaline (NA LC) (3) serotonin (5-HT DRN, MRN) (4) histamine (HA TMN) (5) glutamate (GLU mPRF, BFB, thalamus) (6) orexin (OX LH) and (7) dopamine (DA VTA, SNc) (Zoltoski et al, 1999 Monti, 2004). 

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