Receptor Kanal Ion

RESEPTOR Kanal Ion

(IONOTROPIK RESEPTOR)

A motor nerve cell and

investing membranes

Neurons: cell body, dendrite, axon

Glucose: ~100 g/day

Ionic gradients across membrane

Blood-brain barrier: water soluble

molecules by transporters

glucose, O2 etc

The Nervous System

Neurotransmitter-gated ion channel receptors

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

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

+ choline Acetyl-CoA Pyruvate

PDH complex

(FAD, lipoamide, TPP)

Choline acetyltransferase (CAT)

(inhibited by mercurials)

Acetylcholine

Acetylcholinesterase (AChE) (membrane associated; inhibited by

nerve agents, sarin) Acetate + choline

Reuptake

or diet

Acetylcholine neurotransmission

1. Acetylcholine synthesized from

choline and acetyl CoA by choline

acetyltransferase (ChAT)

2. ACh loaded into synaptic vesicles

by VAchT

3. Released ACh broken down by

acetylcholinesterase (notable

difference from other neuro-

transmitters discussed so far)

4. 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-γ-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 competitive

SR95531 (gabazine) competitive

Picrotoxin mixed competitive, non-competitive

Penicillin G open channel block

Pentelenetetrazole (PTZ) open channel block

Pregnenolone sulfate 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

NMDA

KA

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