RESEPTOR Kanal Ion

(IONOTROPIK RESEPTOR)

The Nervous System

Neurons: cell body, dendrite, axon

Glucose: ~100 g/day
Ionic gradients across membrane
Blood-brain barrier: water soluble
molecules by transporters
glucose, O2 etc

A motor nerve cell and

investing membranes

Ligand-Gated Ion Channel Receptors

Nerve-nerve or nerve-muscle synapsis

Very rapid (msec) with minimal
enzymatic steps
Neurotransmitters (amino acid
derivatives etc) released from vesicles.
Low affinity (mM-mM Kd): rapid
association/dissociation

Neurotransmitter-gated ion channel receptors

Neurotransmitters
Excitatory neurotransmitters
(depolarizing)
Acetylcholine
Aspartate
Dopamine
Histamine
Epinephrine
Glutamate
Inhibitory neurotransmitters
(Hyperpolarizing)
4-Aminobytyrate (GABA)
Glycine
Taurine

RESEPTOR
ASETILKOLIN
NIKOTINIK

Acetylcholine Synthesis and Degradation

PDH complex
(FAD, lipoamide, TPP)
Pyruvate

Acetyl-CoA

+ choline

Choline acetyltransferase
(CAT)
(inhibited by mercurials)

Reuptake
or diet

Acetylcholine
Acetylcholinesterase (AChE)
(membrane associated; inhibited by
nerve agents, sarin)

Acetate

+ choline

Acetylcholine neurotransmission
1.
2.
3.

4.

Acetylcholine synthesized from

choline and acetyl CoA by choline
acetyltransferase (ChAT)
ACh loaded into synaptic vesicles
by VAchT
Released ACh broken down by
acetylcholinesterase (notable
difference from other neurotransmitters discussed so far)
Choline taken up by presynaptic
terminal as precursor to further
ACh synthesis

Antagonis Reseptor Nikotinik

- Letak reseptor: ganglia otonom, NMJ

- Contoh obat pemblok ganglion :
heksametonium, trimetafan tidak
digunakan lagi karena efek pada aksi
simpatik dan parasimpatik ESO besar
- Obat pada NMJ : non-depolarizing
blocking agent dan depolarizing blocking
agent

Agonis Reseptor Nikotinik

- Contoh senyawa/obat : Nikotin, Lobelin

- Nikotin : berikatan dengan Reseptor
asetilkolin nikotinik di SSP
peningkatan kewaspadaan, euforia
ringan, mual dll
- Obat untuk membantu mengatasi gejala
putus rokok : Vareniklin

RESEPTOR GABA

GABA--Aminobutyric acid
The chief inhibitory neurotransmitter in the
mammalian central nervous system
Neurons that produce GABA as their output are
called GABAergic neurons

GABAA a ligand-gated ion channel

GABAB-a G protein-coupled
receptor
Composed of two subunits
When binding to the GABAB receptor activates
the trimeric G protein
Inhibit voltage-gated Ca++ channels
or activate K+ channels.

synthesis

Amino acids

Function class

Secretion sites

GABA

Inhibitory

CNS; invertebrate
neuromuscular junction

Glutamate

Excitatory

CNS; invertebrate
neuromuscular junction

Glycine

Inhibitory

CNS

GABA receptors:
Fast GABA transmission mediated mainly by GABAA
receptors, which are ligand-activated chloride channels.
Some fast GABA transmission mediated by so-called GABAC
receptors, which are a closely-related sub-family of GABAA
receptors
GABA also utilizes a metabotropic receptor called the
GABAB receptor, described in Neuromodulation section.

GABAA receptor pharmacology

Antagonists:
Bicucculine
SR95531 (gabazine)
Picrotoxin

competitive
competitive
mixed competitive, non-competitive

Penicillin G
Pentelenetetrazole (PTZ)
Pregnenolone sulfate

open channel block

open channel block
non-competitive

Agonist:
Muscimol
Barbiturates, neurosteroids (high concentrations)
Enhancers:
Benzodiazepines
Barbiturates, neurosteroids (low concentrations)

GABAA receptor antagonists are important research tools, but not

clinically useful. GABAA receptor enhancement, but not direct
agonism, is useful therapeutically in neurology.

RESEPTOR
GLUTAMAT

glutamate receptor (GluR) is the most important

excitatory transmitter in the CNS

Ionotropic Glutamate
Receptors

AMPA

KA

NMDA

Structure

Ionotropic Glutamate Receptors

AMPA-R

NMDA-R

NMDA receptors

RESEPTOR
SEROTONIN

5-Hydroxytryptamine
(Serotonin)

Derived from tryptophan

Terminated by reuptake
Serotonin deficiency: depression
Paxil, Prozac, Zoloft: antidepressants

Degradation of serotonin

Ionotropic receptors