88813-36-9 Usage
Structure
GAL is a 29-aa C-terminally amidated peptide, apart
from human GAL, which has 20 aa and no amidated
N-terminus. The N-terminal 1–15 aa are highly
conserved.??Human proGAL: Mr 13,302.1, pI 6.84. Soluble in water
and physiological saline solution.
Gene, mRNA, and precursor
The GAL gene is located on human chromosome
11q13.2, rat chromosome 1q42, and mouse chromosome
19A. The peptide precursor of GAL is encoded by a
single-copy gene consisting of six small exons spanning
about 6 kb of genomic DNA. Regarding its structure, a
sequence of GAL is followed by the signal peptide, and
the remainder is called the GAL message-associated
peptide (GMAP).?GAL is widely expressed in the central and peripheral
nervous systems in many mammalian species. In the
brain, GAL is synthesized in the dorsal raphe nucleus,
locus coeruleus, rostral ventrolateral medulla, central
nucleus of the amygdala, paraventricular nucleus, and
supraoptic nucleus. GAL is also found in the spinal cord
and gut.
Synthesis and release
GAL colocalizes in vasopressin neurons and increases
during salt loading, suggesting its influence on osmotically stimulated vasopressin release. GAL gene expression in magnocellular neurons is increased by estrogen.
Receptors
GAL receptors have three subtypes, referred to as GAL
receptor types 1, 2, and 3 (GALR1, GALR2, and GALR3).6
The human GALR1 gene contains three exons and is
translated into a 349-aa protein. The homology between
species is 93% for rat and human GALR1. The expression
of GALR1 is regulated by cAMP through the transcription
factor CREB. Human GALR2 has 92% sequence identity
to rat GALR2, although there is a 15-aa extension of the
C-terminal end in human GALR2. The GALR2 gene is
expressed more ubiquitously compared with that of
GALR1, as it is found in several peripheral tissues, including the pituitary gland, gastrointestinal tract, skeletal
muscle, heart, kidney, uterus, ovary, and testis, in addition to the central nervous system. The Galr3 transcript
was first isolated from rat hypothalamic cDNA libraries.
Human GALR3 consists of 368 aa and shares 36% identity
with human GALR1, 58% with human GALR2, and
approximately 90% with rat GALR3.
Agonists and Antagonists
M617 (GALR1), M1153, M1145 (GALR2).?M35 and galantide (nonselective GALR antagonists),
RWJ-57408 (GALR1), M871 (GALR2), and SNAP37889
and SNAP398299 (GALR3).
Biological functions
In rats, GALR1 is prominently distributed in the hypothalamus, amygdala, hippocampus, thalamus, brainstem, spinal cord, dorsal root ganglion (DRG), gut,
heart, lung, kidney, muscle, adipocytes, and testis.
GALR2 mainly exists in the cortex, hypothalamus, hippocampus, amygdala, cerebellum, DRG, heart, liver, lung,
kidney, intestine, uterus, ovary, stomach, pancreas, and
testis. GALR3 is found in the hypothalamus, dorsal raphe
nucleus, locus coeruleus, and amygdala. GAL is thought
to regulate numerous physiological processes in the adult
mammalian nervous system, including sleep/wake regulation, energy and osmotic homeostasis, reproduction,
nociception, and cognition.
Clinical implications
GAL increases food intake and body weight via
GALR1. Intranasal administration is an effective route
for the delivery of GAL-related agents into the brain by
use of various cyclodextrins. Thus, the intranasal administration of a GALR1 antagonist offers an attractive
approach to combat obesity. Clinical studies indicated
that the GAL concentration is correlative to the morbidity
of type 2 diabetes mellitus in humans. In addition,
some clinical studies have shown that the activation of
the GAL pathway is effective in treating type 2
diabetes.
Description
GAL is expressed in the brain and peripheral organs, and
has diverse physiological actions, including energy homeostasis, reproduction, nociception, and cognition. GAL was isolated in 1983 from the porcine intestine by
Tatemoto and colleagues. The GAL peptide has been
purified from the chicken, alligator, and fish species,
including trout, tuna, bowfin, dogfish, and sturgeon.
Biological Functions
Galanin is
colocalized with acetylcholine, 5-HT , and NE in neurons or in brain regions implicated in cognitive and
affective behavior, suggesting a possible role in the regulation of 5-HT and NA neurotransmission in
depressive states and during the course of antidepressant therapy. Three galanin receptor subtypes have
been cloned and studied, but little is known about their specific contributions to behavioral processes. In the
CNS, galanin inhibits acetylcholine release, suggesting a possible role for galanin in cholinergic dysfunction;
inhibits neurotransmitter release and neuronal firing rate; and inhibits signal transduction by inhibition of
phosphatidyl inositol hydrolysis, leading to symptoms of depression. Thus, blocking the inhibitory effects of
galanin on monoamine neurotransmitters with galanin receptor antagonists would be predicted to mimic or
augment the action of the other monoamine classes of antidepressants."
Clinical Use
Since its discovery in 1983, the neuropeptide galanin has been found to be involved in a wide range of
functions, including pain sensation, sexual activity, feeding, and learning and memory. Galanin is widely
distributed in the central and peripheral nervous systems and in the endocrine system, and it acts as a
inhibitory neuromodulator of NE and 5-HT in the brain. The 29- to 30-amino-acid sequence of galanin is
conserved (almost 90% among species), indicating the importance of the molecule among species.
Check Digit Verification of cas no
The CAS Registry Mumber 88813-36-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,8,8,1 and 3 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 88813-36:
(7*8)+(6*8)+(5*8)+(4*1)+(3*3)+(2*3)+(1*6)=169
169 % 10 = 9
So 88813-36-9 is a valid CAS Registry Number.
InChI:InChI=1/C146H213N43O40/c1-15-75(10)119(187-123(207)78(13)167-129(213)101(51-84-60-154-68-162-84)182-143(227)110-31-24-42-189(110)116(200)65-161-124(208)93(43-71(2)3)173-130(214)95(45-73(6)7)174-132(216)98(49-82-34-38-88(194)39-35-82)170-114(198)63-159-122(206)77(12)166-141(225)108(66-190)186-137(221)105(55-112(150)196)179-131(215)96(46-74(8)9)183-145(229)120(79(14)192)188-140(224)100(168-113(197)58-148)50-83-59-158-90-28-20-19-27-89(83)90)144(228)184-107(57-118(203)204)139(223)180-104(54-111(149)195)136(220)178-102(52-85-61-155-69-163-85)134(218)172-92(30-23-41-157-146(152)153)127(211)185-109(67-191)142(226)176-99(47-80-25-17-16-18-26-80)133(217)177-103(53-86-62-156-70-164-86)135(219)181-106(56-117(201)202)138(222)171-91(29-21-22-40-147)126(210)175-97(48-81-32-36-87(193)37-33-81)125(209)160-64-115(199)169-94(44-72(4)5)128(212)165-76(11)121(151)205/h16-20,25-28,32-39,59-62,68-79,91-110,119-120,158,190-194H,15,21-24,29-31,40-58,63-67,147-148H2,1-14H3,(H2,149,195)(H2,150,196)(H2,151,205)(H,154,162)(H,155,163)(H,
