DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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Extracellular
NH 3
+
P
1 2 3 4 5 6 7 8 9 10 11 12
P
P
Intracellular
P
KEY
DAT
NET
DAT & NET
Figure 14–8. Structure of the rat 5-HT transport protein. Both the N terminus (NH 3+
) and C terminus (COO − ) are intracellular. These
proteins typically have 12 hydrophobic, membrane- spanning domains with intervening extracellular and intracellular loops. The second
extracellular loop is the largest and contains several potential glycosylation sites (indicated with tree- like symbols). Amino acid
residues which are homologous to those in the DA transporter (DAT) and the NE transporter (NET) are colored, as noted. The most
highly conserved regions of these transporters are located in the transmembrane domains; the most divergent areas occur in the N and
C termini. (Courtesy of Dr. Beth J. Hoffman, Vertex Pharmaceuticals, San Diego.)
COO –
CHAPTER 14
NEUROTRANSMISSION AND THE CENTRAL NERVOUS SYSTEM
to the site of release at the posterior pituitary and does not necessarily
describe all of the actions of the peptides.
Neuromodulators. The distinctive feature of a modulator is that it
originates from non- synaptic sites, yet influences the excitability of
nerve cells. Substances such as CO and ammonia, arising from active
neurons or glia, are potential modulators acting through nonsynaptic
actions. Similarly, circulating steroid hormones, steroids
produced in the nervous system (i.e., neurosteroids), locally released
adenosine, and other purines, eicosanoids, and nitric oxide (NO) are
regarded as modulators and/or neurotransmitters (discussed later).
Neurotrophic Factors. Neurotrophic factors are substances produced
within the CNS by neurons, astrocytes, microglia, or transiently
invading peripheral inflammatory or immune cells that assist neurons
in their attempts to repair damage. The binding of neurotrophic
factors to their receptors genarally promotes receptor dimerization
and protein tyrosine kinase activity in the intracellular domains of the
receptors (Figure 14–5C). Seven categories of neurotrophic peptides
are recognized:
1. classic neurotrophins (nerve growth factor, brain- derived
neurotrophic factor, and the related neurotrophins)
2. neuropoietic factors, which have effects both in brain and in
myeloid cells (e.g., cholinergic differentiation factor [also
called leukemia inhibitory factor], ciliary neurotrophic factor,
and some interleukins)
3. growth factor peptides, such as epidermal growth factor, transforming
growth factors α and β, glial cell–derived neurotrophic
factor, and activin A
4. fibroblast growth factors
5.insulin-like growth factors