7-TM Receptors

7-Transmembrane receptors (7-TM receptors), also known as G-protein-coupled receptors, or GPCRs, are integral
membrane proteins that contain seven membrane-spanning helices. As the name suggests they are coupled to
heterotrimeric G proteins on the intracellular side of the membrane. Upon ligand binding, the GPCR undergoes a
conformational change which is transmitted to the G protein causing activation. Further signal transduction depends
on the type of G protein.

Classification
7-TM receptors are activated by a wide variety of ligands including light, olfactory stimulants, peptides, hormones and
neurotransmitters. They are grouped into 6 classes based on sequence homology and functional similarity:

Class A (or 1) (Rhodopsin-like)

Class B (or 2) (Secretin receptor family)

Class C (or 3) (Metabotropic glutamate/pheromone)

Class D (or 4) (Fungal mating pheromone receptors)

Class E (or 5) (Cyclic AMP receptors)

Class F (or 6) (Frizzled/Smoothened)

Physiology and Disease

The human genome encodes roughly 350 7-TM receptors, of which approximately 150 of these have an unknown
function. They comprise the largest family of receptors in the human genome and because of their large number,
widespread distribution and important roles in cell physiology and biochemistry, they play an important role in
medicine.
Diseases involving mutations of 7-TM receptors are relatively rare, however disorders which involve antibodies
directed against 7-TM receptors are more common. Typically disease can be caused by:

Non-functional receptors (GHRH and familial growth hormone deficiency)

Constitutive activation (Rhodopsin and retinitis pigmentosa)

Changes in ligand binding specificity (Thyroid-stimulating hormone receptor and hyperthyroidism of

pregnancy)

Improper receptor processing (vasopressin receptor and diabetes insipidus)

Antibodies directed against the receptors (Thyroid stimulation hormone receptor and Graves disease)

Constitutively active or inactive G proteins

7-TM receptors are the target of around half of all modern medicinal drugs. Their expression on the cell surface
makes them readily accessible to hydrophilic drugs and their non-uniform expression provides selectivity in activating
or blocking physiological events. Agonists and antagonists of 7-TM receptors are used in the treatment of disease in
every organ system.
Muscarinic receptors are widely distributed throughout the body and control distinct functions according to location
and subtype (M1 - M5).They are predominantly expressed in the parasympathetic nervous system where they exert
both inhibitory and excitatory effects.
Receptor
Subtype

M1

M2

M3

M4

M5

Transduction
Mechanism

PLC (Gq/11)

Adenylyl Cyclase (Gi/o)

PLC (Gq/11)

Adenylyl Cyclase
(Gi/o)

PLC (Gq/11)

Primary
Distribution

Neocortex, hippocampus,
neostriatum, salivary
glands, eye, heart

Brain, heart, smooth muscle,

salivary glands

Smooth muscle, exocrine

glands, brain, autonomic
ganglia, salivary glands

Neostriatum, cortex,
hippocampus,
autonomic ganglia

Substantia nigra, pars

compacta, ventral
tegmental area,
hippocampus

Tissue
Function

Learning and memory,

neuromodulation, Mcurrent inhibition

Bradycardia, smooth muscle

contraction, antinociception,
hyperthermia,
neurotransmitter release
(presynaptic)

Smooth muscle contraction,

gland secretion,
neurotransmitter release
(presynaptic)

Regulation of
dopamine
D1stimulated
locomotor activity

Unknown