Gamma-amino

butyric acid

Jyoti
 Neurotransmitter
Small Molecule
Neuropeptides
neurotransmitter
1.Enkephalins
1.Acetylcholine
2.Endorphins
2.Amino acids
3.Substance P
3.Biogenic amines
4.ATP and other purines
5.Nitric oxide.
 Emerged as a potentially important brain chemical many years ago, but
its significance as a neurotransmitter was realized late.
 Presence in brain was first reported in 1950s by Awapara etal. and by
Roberts and Frenkel.

Brain Decrease in
homogenate glutamate level
incubated with parallel with
glutamate increase in GABA
level
 • Extracts from the central nervous system of mammals contain
material (Factor I) blocks impulse generation in the stretch
Florey, 1954 receptor neurons of the crayfish

• Reported that various substances, applied directly to the cortex or

Hayashi & injected into the carotid artery, inhibits electrically or chemically
Nagai induced convulsions in dogs
(1956)

• Purification of Factor I yielded y-aminobutyric acid (GABA)

demonstrated GABA as a major factor in brain extracts responsible
Bazemore for the inhibitory action of these extracts on the crayfish stretch
etal., receptor system.
1957

Hobbiger, • The effects of GABA in antagonizing the contractions of guinea-pig

and rabbit ileum induced by acetylcholine, nicotine and histamine
1957
 • In the series of experiments the effects of Factor
I on the contractions of the guinea-pig ileum
E. FLOREY AND induced by four drugs have been investigated
H. McLENNAN,1958 • compared with the effects produced by GABA
under the same conditions.

J. Physiol. (I959) I45, 66-76

BY E. FLOREY AND H. McLENNAN
 Studies on the distribution of factor I
in mammalian brain by Elisabeth Florey and Ernst florey (1958)

• Occurs in high
concentration
IN CNS only in the central
nervous system,
but is absent in
peripheral nerves

• Only small amounts

are found in white
IN GREY MATTER matter, cranial
nerves, pineal body
and hypophysis.
 Mimic the physiological and pharmacological
properties of natural transmitter.
 Presence in pre-synaptic neuron.
 Synthesis in pre-synaptic neuron.
 Release from the inhibitory nerve terminal
on stimulation.
 Restrict the release of luteinizing hormone-
releasing hormone before the onset of puberty.
 High level of GABA released in stalk-median
eminence of pre-pubertal mice as compared to
pubertal mice.
 Low levels of LHRH release in the prepubertal
period appear to be due to the dominant
inhibitory mechanism of GABA mediated by the
GABAA receptor
 Removal of this inhibition may trigger an increase
in LHRH release and the onset of puberty.
 Three mechanisms for the reduction in
endogenous GABA release leading to the
increase in LHRH release and the subsequent
initiation of puberty can be speculated:
 Principles of Anatomy and Physiology, GERARD J. TORTORA BRYAN
DERRICKSON
 RONALD HARRIS-WARRICK,Synaptic chemistry in single neurons J Neurophysiol
93:3019-3031,2005
 DAI MITSUSHIMA, DAVID L. HEI, AND Ei TERASAWA, y-Aminobutyric acid is an
inhibitory neurotransmitter restricting the release of luteinizing hormone-
releasing hormone before the onset of puberty. Vol. 91, pp. 395-399, January
1994 Neurobiology
 N.G. BOWERY & T.G. SMART, GABA and glycine as neurotransmitters: a brief
history. British Journal of Pharmacology (2006) 147, S109–S119
 F. HOBBIGER, effects of y-aminobutyric acid on the isolated mammalian
ileum. J. Physiol. (I958) I42, I47-I64
 E. FLOREY AND H. MCLENNAN, the effects of factor I and of gamma-
aminobutyric acid on smooth muscle preparations. J. Physiol. (I959) I45, 66-76
 RICHARD W. OLSEN,TOBIN A J. Molecular biology of GABAA receptors
 ELISABETH FLOREY AND ERNST FLOREY, studies on the distribution of factor
iin mammalian brain. J. Physiol. (I958) I44, 220-228