Neurotransmitters, effect

Hormones, peptides and neurotransmitters Effect of ICV injection on food intake Effect of gene deletion on food intake Response to adiposity signals Receptor Effect of receptor defect on food intake... 

Several proteinogenic amino acids (see p. 60) have neurotransmitter effects. A particularly important one is glutamate, which acts as a stimulatory transmitter in the CNS. More than half of the synapses in the brain are glutaminergic. The metabolism of glutamate and that of the amine GABA synthesized from it (see below) are discussed in more detail on p.356. Glycine is an inhibitory neurotransmitter with effects in the spinal cord and in parts of the brain. 

FIGURE 2.2 The anatomy of the neuron. Communication between two neurons occurs at the synapse. The presynaptic neuron produces and releases the neurotransmitter into the synaptic cleft. Four mechanisms (1 ) are important to understand the function of most neurotransmitter systems. The release of neurotransmitter can be modulated via presynaptic receptors (1). The amount of neurotransmitter in the synaptic cleft can be decreased by reuptake into the presynaptic neuron (2) or via enzymatic degradation. Neurotransmitter effects at the target neuron are relayed via fast-acting ion channel—coupled receptors (3) or via slower-acting G protein—coupled receptors (4). Down-stream effects of postsynaptic receptors include the phosphorylation (P) of nuclear proteins. 

TABLE 5.11. Neurotransmitter Effects of Conventional Antipsychotics and Their Associated Side Effects... 

Adverse reactions with antihistamines are the result of multiple mechanisms (see Figure 13-3). Muscarinic, a-adrenergic, and serotonin receptor blockade may result in mydriasis, dry mouth and eyes, urinary retention, constipation, and dizziness in first-generation antihistamines. When the neurotransmitter effect of histamine is interrupted, various CNS adverse reactions may occur. These side effects include increased sedation, decreased cognitive function, decreased psychomotor function, and headache. 

As might be noted in the preceding description, the specificity of neurotransmitter effects that are mediated by cAMP is determined at three basic levels. First of all, the nature of the neurotransmitter receptor will determine whether membrane-bound adenylate cyclase will be stimulated, inhibited, or left unaffected. Second, the nature, concentration, and intrinsic activity of the protein kinase and the phosphoprotein phosphatase will determine the pattern and degree of protein phosphorylation. Last, the identity and availability of the protein substrates will determine the ultimate biochemical consequences of cAMP elevations. 

The concept that the control of the secretion of stored NGF is achieved by nerve terminals is supported by several studies. Thus, cultured vascular smooth muscle cells increase NGF secretion in response to a-adrenergic agonists, whereas )3-adrenergic agonists inhibit secretion (Creedon and Tuttle, 1991). These authors also found a dissociation between altered mRNA levels and NGF secretion. A direct demonstration of a neurotransmitter effect on NGF release in vivo was provided by White and colleagues (White et al.,... 

Figure 30-2. Possible sites of action of antidepressant drugs. Inhibition of neuronal reuptake of norepinephrine and serotonin increases the synaptic activities of these neurotransmitters. Inhibition of MAO increases the presynaptic stores of both norepinephrine and serotonin, which leads to increased neurotransmitter effects. Blockade of the presynaptic alphag autoreceptor prevents feedback inhibition of the release of norepinephrine. Note These are acute actions of antidepressants.

As an alpha-2 agonist, tizanidine decreases presynaptic excitatory neurotransmitter release and postsyn-aptic neurotransmitter effectiveness. Alpha-2 receptor agonists attenuate monosynaptic and polysynaptic reflexes in the spinal cord [25]. Tizanidine decreases excitatory neurotransmitter release and Substance P release from small sensory afferents [28]. Tizanidine decreases locus coeruleus activity, thereby modulating descending motor regulatory pathways [28]. Tizanidine decreases activity of both alpha and gamma motor neurons [28]. 

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