2. Introduction
Calcitonin gene-related peptide (CGRP) is a member of
the calcitonin family of peptides, which in humans exists in two forms: α-
CGRP and β-CGRP, also known as CGRP I and CGRP II.
α-CGRP is a 37-amino acid neuropeptide and is formed from the
alternative splicing of the calcitonin/CGRP gene located on chromosome 11.
β-CGRP is less studied. In humans, β-CGRP differs from the α-CGRP by
three amino acids and is encoded in a separate gene within the same
vicinity.
The CGRP family includes calcitonin (CT), adrenomedullin (AM), and
amylin (AMY).
3.
4. Discovery
o Canadian scientist Copp postulated the
existence of calcium lowering peptide-CT
o 1961- regulation of parathyroid hormone
o Found 2nd calcium regulating hormone- CT
o 1980- CT gene was cloned
o 1982- CGRP was discovered by molecular
cloning of CT gene
5.
6.
7. Distribution
CNS
• nervous system and discrete brain areas
• co-exists with acetylcholine
• most neurons, both CGRP co-exist but β- CGRP is
predominant in enteric nervous system and pituitary
gland.
PNS
• present in sensory ganglia often stored with
substance P.
8.
9. Receptors
Heteromeric receptor composed of a G protein- coupled
receptor called calcitonin receptor-like receptor (CALCRL)
and a receptor activity-modifying protein (RAMP1).
CGRP receptors are found throughout the body.
May modulate a variety of physiological functions in all
major systems;
respiratory,
endocrine,
gastrointestinal,
immune, and
cardiovascular.
10. Functions
o Role in CNS
- modulate acetylcholine receptor function
o Role in PNS
- modulate antigen presentation in Langerhans cells
- block tolerance to morphine
- potent inhibitor of gastric acid secretion
o Role in CVS
- potent vasodilator, positive ionotropic and
chronotropic effect
o Headache and nociception
o CGRP is known to be closely involved in the cascade of
events that lead to a migraine attack.
