Transcript galanin - Personal Home Pages (at UEL)

GALANIN
BY NKEM UMEOKOLI
MSc Neuropharmacology
University of East London
•Galanin is a 29 amino acid neuro-peptide isolated
from porcine intestine.
•It shows many interesting physiological and
behavioural actions which may be relevant to some
disease states and clinical therapeutics.
•Named from the first and last amino acids in its
porcine sequence - Glycine and Alanine.
•The first 15 amino acids in its peptide sequence
is conserved in a variety of species including
Humans, rats, pigs, cows, dogs, chickens and
alligators.
•NMR analysis of Rat galanin indicates a secondary
structure of two alpha-helices interrupted by a bend
in the proline-13 amino acid residue.
•Galanin is widely distributed in both the central
and the peripheral nervous systems.
•In the CNS: hypothalamus/hippocampus, brain
stem, spinal cord.
•In the peripheral organs: pancreas, adrenal gland,
gastrointestinal tract, genital tract, urinary bladder
•Galanin binds to and acts on G-protein coupled
receptors.
•Only one galanin receptor subtype has been cloned
so far - GalR1.
•Pharmacological evidence suggests more than one
receptor subtype exists.
•Purified galanin receptors from rat and human
brain show a single polypeptide of 54-60 kDa.
•The 1st antagonist for the galanin receptor has
been synthesised called M15 or Galantide.
•Binding of the antagonist to the galanin receptor is
0.2 - 50nM concentration.
Physiological functions of Galanin
• In Alzheimer’s disease
– galanin is elevated
– galanin inhibits acetylcholine release
– Galanin receptor antagonists may enhance
cholinergic transmission.
Galanin stimulates
•food consumption
•release of luteinising hormone
•prolactin release
•growth hormone
•Galanin serves an antinociceptive function in the
spinal cord.
•Galanin agonists may be clinically useful in
potentiating the analgesic actions of morphine.
•Galanin inhibits insulin release, therefore causes
hyperglycemia.
•Galanin may be involved in some forms of human
obesity.
In conclusion
•Galanin is a 29 amino acid neuro-peptide has
inhibitory actions
•Exerts biological effects in mammals such as
feeding, insulin release and growth hormone
release.
•Is involved in the pathogenesis of Alzheimer’s
disease and in antinociception.