17. are the
regulatory macroproteins –
sensitive elements in the
system of chemical commu-
nications that coordinates
the function of the different
cells in the body.
A. Receptors
18. Receptors bind to
•Endogenous ligands (such as):
- neurotransmitters (mediators)
- hormones
- autacoids (tissue mediators)
- grouth factors
- inhibitory factors, etc.
•Exogenous ligands:
- many (but not all) drugs
- some other xenobiotics
20. The interaction between the ligand
and the receptor does not involve
covalent bonds but weaker,
reversible forces, such as:
•Ionic bonding
•Hydrogen bonding
•Hydrophobic bonding
•Van der Waals forces.
21. The receptors have a three-dimensional
organization in space and require the
different aspects of a ligand to be pre-
sented in the correct 3-D configuration
(like fitting a hand into the glove).
22. The numbers of receptors may be
altered during chronic drug treatment,
with either an increase in receptor
numbers (up-regulation) or a decrease
(down-regulation).
The therapeutic effect of β-blockers
develops slowly. This is probably
related to adaptive regulation
of receptor numbers.
23. There are pre- and
postsynaptic receptors.
Presynaptic receptors
may inhibit or increase
transmitter release
(feedback mechanism: +/-)
24. a
PresynapticPresynaptic receptors in adrenergic synapsereceptors in adrenergic synapse
and their role in the regulative negative andand their role in the regulative negative and
positive feedbackpositive feedback
25. There are 4 main types of recep-
tors, according to their molecu-
lar structure and the nature of
receptor-effector linkage.
The location of type 1, 2 and 3
receptors is on (into) the cell
membranes; type 4 − into the
cell nucleus.
26. Ionotropic receptors
(ligand-gated ion channel receptors)
•These receptors are involved
mainly in fast synaptic transmission.
•They are proteins containing several
transmembrane segments arranged
around a central channel.
•Ligand binding and channel opening
occur on a millisecond time-scale.
30. Antiseizure drugs, induced reduction of
current through T-type Ca2+
channels.
Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006)Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006)
(-)(-)
31. G-protein-coupled receptors
All comprise 7 membrane-spanning
segments. One of the intracellular
loops is larger than the others and
interacts with G-protein.
32. •The G-protein is a membrane protein
comprising 3 subunits (α, β, γ). The
alpha-subunit possessing GTP-activity.
•When the agonists occupy a receptor,
the alpha-subunit dissociates and
is then free to activate a target
(effector):
- enzyme (AC, GC, PLC)
- Ca2+
ion channels
33. • AC (adenylate cyclase) catalyses
formation on the intracellular
messenger (cAMP).
• cAMP activates various protein
kinases (PKA and others) which
control cell function in many
different ways by causing phos-
phorylation of various enzymes,
carriers and other proteins.
39. • PLC (phospholipase C) catalyses the
formation of two intracellular messen-
gers − InsP3 and DAG, from memb-
rane phospholipids.
• InsP3 (inositol-triphosphate) increases
free cytosolic calcium by releasing
Ca2+
from the endoplasmic reticulum.
• Free calcium initiates contractions, se-
cretion, membrane hyperpolarization
• DAG activates protein kinase C (PKC).
44. •Incorporate thyrosine kinase
in their intracellular domain.
•These receptors are involved
mainly in events controlling
phosphorilation, cell growth
and differentiation.
Tyrosine-kinase receptors
46. • They are nuclear proteins, so
ligands must first enter cells.
• Receptors have DNA-binding
domain.
• Stimulation of these receptors
increase protein synthesis by
the activation of DNA transcription.
Nuclear receptors
48. a) Cytoplasmic receptors:
Steroid hormones, Calcitriol
Steroide hormone diffuse into the cell. When activated, the
receptors translocate to the nucleus where they can upregulate
gene transcription by action on specific DNA response elements
and recruiting co-activator proteins.
49. b) Directly at nuclear receptors:
Thyroid hormones (T3, T4)
T3 or T4 penetrate the nucleus
Combine with their receptors
Alters DNA-RNA mediated
protein synthesis
56. Most drug produce graded
dose-related effects, which can be
plotted as a dose response curve.
Such curves are often hyperbolic (a),
but they can be conveniently
plotted on semi-logarithmic paper
to give sigmoidal shape (b).
58. The method of plotting dose-response
curves facilitates quantitative analysis
of: full agonists, which produce
graded responses up to maximum
value; antagonists, which produce no
response on their own but antagonize
the response to an agonist; partial
agonists, which produce some response
but to a lower maximum than that of
a full agonist and antagonize its effect.
59. •The affinity of a drug is its ability
to bind to the receptor.
•The intrinsic activity of a drug is
its ability after binding to the receptor
to produce effect.
•The efficacy of a drug is its ability
to produce maximal response.
•The selectivity of a drug is the extent
to which it acts preferentially on
particular receptor types.
62. Dose-response curve of two full
agonists (A, B) of different
potency, and a partial agonist (C).
63. In the clinical situation
dose-response curves are
influenced by many factors
including genetic, as well as
age, weight, nutrition;
psychological and social
factors (that strongly influence
compliance and placebo effect).