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S e m e s t e r G a s a l T. A 2 0 1 9 / 2 0 2 0

G-Protein Coupled Receptors (GPCRs)

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oleh:

Yance Anas, M.Sc., Apt.

Bag. Farmakologi & Toksikologi

Fakultas Farmasi Universitas Wahid
Hasyim Semarang
 G-Protein Coupled Receptors (GPCRs)
Also Knows:
• G Protein-linked receptors
• G Protein-link to 2nd Massangers
• Seven-Transmembrane Receptors (7-TMR)
• “G Protein”
Juga tahu: G protein-Linked reseptor G protein-link ke 2 Massangers tujuh-
Transmembrane reseptor (7-TMR) "G protein" Guanine protein
nukleotida-mengikat guanosin triphospate = GTP guanosin diphospate =
PDB
G-Protein Coupled Receptors (GPCRs)
 G-Protein Coupled Receptors (GPCRs)

• Sangat penting secara fisiologis

• Hanya ditemukan di eukariota
• Dua jalur sinyal transduksi utama
• cAMP-dependent pathway
– IP3/DAG pathway
 Nature Reviews Molecular Cell Biology 3, 639-650 (2002)
SEVEN-TRANSMEMBRANE RECEPTORS

• Kristen L. Pierce, Richard T. Premont & Robert J. Lefkowitz

• The Howard Hughes Medical Institute and the Departments of Medicine and Biochemistry,
Box 3821, Duke University Medical Center, Durham, North Carolina, 27710, USA.

• Disebut sebagai Seven-transmembrane

receptors
• Merupakan jenis reseptor
transmembran terbanyak (dalam tubuh)
• Terdapat pada semua jaringan tubuh
• Merupakan target aksi sebagian besar
obat-obatan.
 SEVEN-TRANSMEMBRANE RECEPTORS
Extracellular
loops NH2

N -Terminal chain

Membrane VII VI
Transmembrane
V IV III II I helix

G-Protein
binding region

HO2C
Variable
C -Terminal chain
intracellular loop Intracellular loops
Struktur Dasar
• 7 Transmembrane Domains (TMDs),
• 3 intracellular loops,
• 3 extracellular loops, Pharmacol Ther. 2004 Jul;103(1):21-80
• N- and C-teminals
Basic structure: GPCRs are lipoproteins
Diversity of GPRS Receptors

The EMBO Journal (1999) 18, 1723–1729

large variety of different agonists
 Diversity of physiological responses to GPCR stimulation
TARGET TISSUE HORMONE MAJOR RESPONSE
Thyroid gland thyroid-stimulating hormone thyroid hormone synthesis and
(TSH) secretion
Adrenal cortex adrenocorticotrophic hormone cortisol secretion
(ACTH)
Ovary luteinizing hormone (LH) progesterone secretion
Muscle adrenaline glycogen breakdown
Bone parathormone bone resorption
Heart adrenaline increase in heart rate and force
of contraction
Liver glucagon glycogen breakdown
Kidney vasopressin water resorption
Fat adrenaline, ACTH, glucagon, triglyceride breakdown
TSH

TARGET TISSUE SIGNALING MOLECULE MAJOR RESPONSE

Liver vasopressin glycogen breakdown
Pancreas acetylcholine amylase secretion
Smooth muscle acetylcholine contraction
Blood platelets thrombin aggregation
Receptor activation of heterotrimeric G-proteins.
Basic model

Hollinger et al. 2000 Pharmacological Reviews

 What are “G Proteins”?
• Protein yang mengikat GTP hetertrimeric,
terdiri dari 3 subunit:
• Subunit α
• Subunit β
• Subunit γ
 What are G Protein-linked 2nd massangers

• Target selular (protein/enzim) dengan fungsi tertentu (mis: membuat

produk) ketika berinteraksi dengan “protein G”
What are G Protein-linked 2nd massangers
Two important Signal Pathway
Two important Signal Pathway
Two important Signal Pathway
Two important Signal Pathway
Two important Signal Pathway
Two important Signal Pathway
 Two important Signal Pathway

C-AMP dependent pathway IP3/DAG Pathway

• Gi • Gq
M2, α2, D2 H1, α3, V1, M1, M3
• Gs
Β1, β2, D1, H2, V2