Central nervous system neurotransmission

Cholinergic neurotransmission ChEs terminate cholinergic transmission in the central nervous system (CNS), in NMJs and in the autonomic system (the parasympathetic system, somatic motor nerves and pre-ganglionic sympathetic nerves). A few sensory cells and the NMJ in nematodes also include ChEs. 

Somatostatin is a regulatory cyclic peptide, which has originally been described as a hypothalamic growth hormone release-inhibiting factor. It is produced throughout the central nervous system (CNS) as well as in secretoty cells of the periphery and mediates its regulatory functions on cellular processes such as neurotransmission, smooth muscle contraction, secretion and cell proliferation via a family of seven transmembrane domain G-protein-coupled receptors termed sstx 5. 

Rgure 22-2. Neurotransmission in the central nervous system. Neurotransmitter molecules (eg, norepinephrine), released by the presynaptic nerve, cross the synapse and bind with receptors in the cell membrane of the postsynaptic nerve, resulting in the transmission of the nerve impulse. 

Bloom, F., Neurotransmission and the central nervous system, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill, New York, 1996, chap. 12. 

Ionotropic glutamate receptors mediate fast excitatory neurotransmission in practically all areas of the central nervous system (CNS). They are also critical for both the induction and expression of synaptic plasticity, and have been implicated in diverse pathological conditions, such as epilepsy, ischemic brain damage, anxiety, and addiction. There are three subtypes of ionotropic glutamate receptors that are named after their high-affinity agonists as a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), N-1nethyl-D-aspartate (NMDA), and kainate (KA) receptors (1). 

Mechanism of Action A benzodiazepine that enhances action of gamma-aminobutyric acid (GABA) neurotransmission in the central nervous system (CNS). Therapeutic Effect Produces depressant effect at all levels of CNS. 

None of the TCAs seem to have an effect on dopaminergic neurotransmission in the central nervous system (CNS). This has been supported by the lack of alterations in dopamine receptor sensitivity in chronically treated patients who have shown response to treatment (Sugrue, 1983). More recent investigations have also shown that administration of DMI to depressed subjects had no effect on levels of homovanillic acid, the principal metabolite of dopamine, in a measure of brain neurotransmitter production. In this investigation, DMI administration did increase norepinephrine production and overall cerebral metabolism (Lambert, 2000). 

Neurotrophic factors responsible for neuronal survival, dendritic proliferation, and the activation of the different neurotransmission systems are present in the central nervous system [CNS). The most well-known one is the NGF, a peptidergic complex of 140 kd and with a sedimentation coefficient of 7s. NGF has three subunits, a, p, and y. Subunit p is the active part of the molecule. Other neurotrophic factors [F. ffefti 1994) include 1) brain-derived neurotrophic factor [BDNF), 2) neurotrophin 3, 3) neurotrophin 4/5, and 4) ciliary neurotrophic factor. 

The D (R) isomer of the amino acid A-methyl aspartate, more familiarly known as NMDA, serves as the endogenous agonist at a number of central nervous system (CNS) receptor sites. This agent is not only involved in neurotransmission, but it also modulates responses elicited by other neurochemicals. 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

In Chapter 1 we discussed how modern psychopharmacology is essentially the study of chemical neurotransmission. In this chapter we will become more specific and discuss how virtually all central nervous system (CNS) drugs act in one of two very specific ways on chemical neurotransmission first and most prominently as stimulators (agonists) or blockers (antagonists) of neurotransmitter receptors or second, and less commonly, as inhibitors of regulatory enzymes. 

Opiates act on a variety of receptors. The three most important subtypes are the mu, delta, and kappa opiate receptors (Fig. 13—25). The brain makes its own endogenous opiate-like substances, sometimes referred to as the brain s own morphine. They are peptides derived from precursor proteins called pro-opiomelanocortin (POMC), proenkephalin, and prodynorphin. Parts of these precursor proteins are cleaved off to form endorphins or enkephalins, stored in opiate neurons, and presumably released during neurotransmission to mediate endogenous opiate-like actions (Fig. 13-25). However, the precise number and function of endogenous opiates and their receptors and their role in pain relief and other central nervous system (CNS) actions remain largely unknown. 

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