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

Transient receptor potential (TRP) channels,
are a family of hexaspanning receptors with a cationpermeable
pore domain between the fifth and sixth
transmembrane segments, and a common 25-amino
acid TRP box C- terminal to the sixth transmembrane
domain. TRP channels are responsive to multiple
stimuli and play crucial roles in sensory
physiology, including thermosensation, osmosensation,
and taste. Members of the IRPV subfamily
(vanilloid receptors) interact with numerous ligands,
including the endogenous cannabinoid, anandamide,
and the chili pepper ingredient, capsaicin (Ramsey
et al., 2006).
NEUROTRANSMITTER RECEPTOR-
EFFECTOR COUPLING IN THE CNS
A number of molecular mechanisms have been identified
that link receptor occupancy to biological responses
(Figure 14–5). The most commonly seen post- receptor
events are changes in ion flux through channels formed
by a multi- subunit receptor complex (Figures 14–2 and
14–3). The change in permeability is a characteristic of
the specific receptor. For example, activation of N- AChR
or NMDA receptors results in depolarization by increasing
the permeability to Na + (as well as Ca 2+ ). GABA
and glycine a receptor are generally hyperpolarizing,
371
CHAPTER 14
A
Neurotransmitter
Plasma
membrane
C
Neurotrophic factors
Protein
tyrosine
kinase
Receptor
Ion channel
Substrates,
scaffold proteins
B
D
α
Receptor
β γ
Steroid
hormone
Ion channel
Steroid
receptor
Altered gene
expression
α
Effectors (AC, PLC)
Second messengers (cAMP, Ca 2+ )
Ion
channel
Altered protein kinase/phosphatase activities
Effects on other neuronal processes
Effects on
other
neuronal
processes
β γ
NEUROTRANSMISSION AND THE CENTRAL NERVOUS SYSTEM
Nucleus
DNA
Figure 14–5. General Patterns of Signal Transduction in the Brain. A. Neurotransmitter activation of a receptor that contains an integral
ion channel. B. Neurotransmitter activation of G protein- coupled receptor. After activation, the βγ subunits of the G protein can directly
regulate an ion channel (left), and the α subunit can activate second messenger- dependent signaling involving protein kinases and protein
phosphatases, which can, in turn, affect ion channels and other neuronal processes (right). C. Neurotrophic factors promote receptor
dimerization, which leads to activation of receptor protein tyrosine kinase activity and its sequelae. D. Steroid hormone activation of
a cytoplasmic receptor. After the receptor- hormone complex forms, it enters the nucleus and regulates gene expression (see Figure 6–12).
(Redrawn with permission from Nestler EJ, Hyman SE, Malenka RC (eds). Molecular Neuropharmacology. New York: McGraw-Hill,
2000, p 76. Copyright © 2009 by The McGraw-Hill Companies, Inc. All rights reserved.)