| 1. Urocortin
III (Human) is identical with Stresscopin (3-40)-NH2
(Human).
2. Urocortin II (Urocortin Related Peptide,
URP) (Human) is identical with Stresscopin Related
Peptide (6-43)-NH2 (Human).
References:
Lewis, K. et al. Proc. Natl. Acad. Sci. USA
98, 7570-7575, 2001 (June 19);
Hsu, S.Y. & Hsueh, A.J.W. Nature Medicine,
7 605-611, 2001
Review by Jun Yang on June 21, 2001
Urocortin reduces food intake and gastric
emptying in lean and ob/ob obese mice
BACKGROUND & AIMS: Gastric emptying plays
an important role in regulating food intake.
This study was designed to investigate whether
intraperitoneally injected urocortin reduces
gastric emptying, feeding, and body weight in
lean and ob/ob obese mice. METHODS: Food intake
and body weight were measured after intraperitoneal
injections of one of the following: urocortin,
deamidated form of urocortin (urocortin OH),
corticotropin-releasing factor (CRF), CRF6-33,
cholecystokinin octapeptide (CCK-8), and leptin
in 16-hour food-deprived animals. Gastric emptying
was assessed 2, 4, or 8 hours after intraperitoneal
injection. Repeated injections of urocortin
were continued for 5 days in ob/ob mice. RESULTS:
Urocortin (0.003-3 nmol) dose-dependently and
potently decreased food intake and body weight
gain in lean mice. The ranking order of potency
was urocortin > urocortin OH >/= CRF >
CCK-8 > CRF6-33 > leptin. Gastric emptying
was also potently reduced by urocortin with
a similar ranking order of potency of urocortin
> CRF > urocortin OH > CCK-8. Simultaneous
administration of urocortin and CRF receptor
antagonist, alpha-helical CRF9-41, blocked the
effects of urocortin. Urocortin reduced food
intake and body weight gain, as well as the
rate of gastric emptying, in ob/ob mice, which
was significantly faster than that of lean mice.
Five daily injections of urocortin significantly
lowered body weight and improved glycemic control
in ob/ob mice. CONCLUSIONS: The urocortin-induced
decrease in food intake and body weight in lean
and ob/ob mice is closely related to gastric
emptying and opens new possibilities for the
treatment of obesity.
Asakawa A, Inui A, Ueno
N, Makino S, Fujino MA, Kasuga M. Gastroenterology
1999 Jun;116(6):1287-92
Urocortin
reduces oxygen consumption in lean and ob/ob
mice
A vast number of intensive studies
have been undertaken to clarify the mechanisms
of energy balance. This study was undertaken
to investigate the effect of urocortin, an endogenous
ligand for corticotropin-releasing factor (CRF)
type 2 receptor, on oxygen consumption in lean
and genetically obese (ob/ob) mice. Oxygen consumption
was measured after intraperitoneal injection
in unrestrained mice at an environmental temperature
of 22 degrees C of one of the following: urocortin,
deamidated form of urocortin (urocortin OH)
or CRF. The intraperitoneal injection of urocortin
(0.3-3 nmol) dose-dependently decreased oxygen
consumption in lean mice. The inhibitory effect
induced by urocortin was more potent than that
induced by CRF or urocortin OH. The ranking
potency was urocortin > urocortin OH >
CRF. Urocortin significantly reduced oxygen
consumption in ob/ob mice as well as in lean
mice. These results suggest that urocortin decreases
oxygen consumption, and that the CRF type 2
receptor may influence energy balance in lean
and ob/ob mice.
Asakawa A, Inui A, Ueno
N, Makino S, Fujimiya M, Fujino MA, Kasuga M.
Int J Mol Med 2001 May;7(5):539-41
Rat brain tissue was stained with Urocortin
Antibody (catalog No.: H-019-06)
| Rat brain
tissue was stained with Urocortin Antibody
(catalog No.: H-019-06) |
|
Human Urocortin II (Urocortin Related Peptide,
URP) is identical with Stresscopin Related Peptide
(SRP) (6-43)-NH2 (Human).
Human Urocortin III is identical with human
Stresscopin (3-40)-NH2
References:
Lewis, K. et al. Proc. Natl. Acad. Sci. USA
98, 7570-7575, 2001 (June 19)
Hsu, S.Y. & Hsueh, A.J.W. Nature Medicine,
7 605-611, 2001
Review by Jun Yang on June 21, 2001
 |
Amino Acid Sequence of Prepro-Urocortin
II (Mouse)
|
 |
| |
| 1 |
|
M |
T |
R |
W |
A |
L |
V |
V |
F |
V |
V |
L |
M |
L |
D |
R |
I |
L |
F |
V |
|
20 |
| 21 |
|
P |
G |
T |
P |
I |
P |
T |
F |
Q |
L |
L |
P |
Q |
N |
S |
L |
E |
T |
T |
P |
|
40 |
| 41 |
|
S |
S |
V |
T |
S |
E |
S |
S |
S |
G |
T |
T |
T |
G |
P |
S |
A |
S |
w |
S |
|
60 |
| 61 |
|
N |
S |
K |
A |
S |
P |
Y |
L |
D |
T |
R |
V |
I |
L |
S |
L |
D |
V |
P |
I |
|
80 |
| 81 |
|
G |
L |
L |
R |
I |
L |
L |
E |
Q |
A |
R |
Y |
K |
A |
A |
R |
N |
Q |
A |
A |
|
100 |
| 101 |
|
T |
N |
A |
Q |
I |
L |
A |
H |
V |
G |
R |
R |
|
|
|
|
|
|
|
|
|
112 |
|
|
 |
 |
 |
Human Urocortin II, a Selective
Agonist for the Type 2 Corticotropin-Releasing
Factor Receptor, Decreases Feeding and Drinking
in the Rat
Corticotropin-releasing factor (CRF) has been
hypothesized to modulate consummatory behavior
through the Type 2 CRF (CRF(2)) receptor. However,
behavioral functions subserved by the CRF(2)
receptor remain poorly understood. Recently,
human urocortin II (hUcn II), a selective CRF(2)
receptor agonist, was identified. To study the
effects of this neuropeptide on ingestive behavior,
we examined the effects of centrally infused
hUcn II (i.c.v. 0, 0.01, 0.1, 1.0, 10.0 &mgr;g)
on the microstructure of nose-poke responding
for food and water in nondeprived, male rats.
Malaise-inducing properties of the peptide were
monitored using conditioned taste aversion (CTA)
testing. To identify potential sites of action,
central induction of Fos protein expression
was examined. hUcn II dose dependently reduced
the quantity and duration of responding for
food and water at doses lower (0.01-1.0 &mgr;g)
than that forming a CTA (10 &mgr;g). Effects
were most evident during hours 4 to 6 of the
dark cycle. Meal pattern analysis showed that
hUcn II potently (0.1 &mgr;g) increased
the satiating value of food. Rats ate and drank
smaller and shorter meals without changing meal
frequency. Rats also ate more slowly. hUcn II
induced Fos in regions involved in visceral
sensory processing and autonomic/neuroendocrine
regulation and resembling those activated by
appetite suppressants. hUcn II is a promising
neuropeptide for investigating the role of the
CRF(2) receptor in ingestive behavior.
Inoue K,et al. J Pharmacol
Exp Ther 2003 Apr 1;305(1):385-393
Human urocortin II, a new CRF-related
peptide, displays selective CRF(2)-mediated
action on gastric transit in rats
Human urocortin (hUcn) II is a new member of
the corticotropin-releasing factor (CRF) family
that selectively binds to the CRF(2) receptor.
We investigated the CRF receptors involved in
mediating the effects of hUcn II and human/rat
CRF (h/rCRF) on gut transit. Gastric emptying,
4 h after a solid meal, and distal colonic transit
(bead expulsion time) were monitored simultaneously
in conscious rats. CRF antagonists were given
subcutaneously 30 min before intravenous injection
of peptides or partial restraint (for 90 min).
hUcn II (3 or 10 microg/kg i.v.) inhibited gastric
emptying (by 45% and 55%, respectively) and
did not influence distal colonic transit. The
CRF(2) peptide antagonist astressin(2)-B blocked
hUcn II action. h/rCRF, rat Ucn, and restraint
delayed gastric emptying while accelerating
distal colonic transit. The gastric response
to intravenous h/rCRF and restraint was blocked
by the CRF(2) antagonist but not by the CRF(1)
antagonist CP-154,526, whereas the colonic response
was blocked only by CP-154,526. None of the
CRF antagonists influenced postprandial gut
transit. These data show that intravenous h/rCRF
and restraint stress-induced delayed gastric
emptying involve CRF(2) whereas stimulation
of distal colonic transit involves CRF(1). The
distinct profile of hUcn II, only on gastric
transit, is linked to its CRF(2) selectivity.
Million M, et al. Am J
Physiol Gastrointest Liver Physiol 2002 Jan;282(1):G34-40
Differential actions of peripheral
corticotropin-releasing factor (CRF), urocortin
II, and urocortin III on gastric emptying and
colonic transit in mice: role of CRF receptor
subtypes 1 and 2
Peripheral CRF inhibits gastric emptying and
stimulates colonic motor function in rats. We
investigated the role of CRF(1) and CRF(2) receptors
in i.p. CRF-induced alterations of gut transit
in conscious mice using selective CRF(1) and
CRF(2) ligands injected i.p. Gastric emptying
2 h after ingestion of a solid chow meal and
colonic transit (time to expel a bead inserted
into the distal colon) were determined simultaneously.
Rat/human (r/h)CRF, which has CRF(1) > CRF(2)
binding affinity, decreased distal colonic transit
time at lower doses (6-12 microg/kg) than those
inhibiting gastric emptying (20-60 microg/kg).
Ovine CRF, a preferential CRF(1) receptor agonist
(6-60 microg/kg), reduced significantly the
colonic transit time without altering gastric
emptying, whereas the selective CRF(2) receptor
agonists mouse urocortin II (20-60 microg/kg)
and urocortin III (120 microg/kg) inhibited
significantly gastric emptying without modifying
colonic transit. The CRF(1)/CRF(2) receptor
antagonist, astressin (30-120 microg/kg), dose
dependently prevented r/hCRF (20 microg/kg)-induced
inhibition of gastric emptying and reduction
of colonic transit time. The selective CRF(1)
receptor antagonists, NBI-27914 (C(18)H(20)Cl(4)N(4)C(7)H(8)O(3)S)
and CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]e
thylamine) (5-30 mg/kg), dose dependently blocked
r/hCRF action on the colon without influencing
the gastric response, whereas the CRF(2) receptor
antagonist, antisauvagine-30 (30-100 microg/kg),
dose dependently abolished r/hCRF-induced delayed
gastric emptying and had no effect on colonic
response. These data show that i.p. r/hCRF-induced
opposite actions on upper and lower gut transit
in conscious mice are mediated by different
CRF receptor subtypes: the activation of CRF(1)
receptors stimulates colonic propulsive activity,
whereas activation of CRF(2) receptors inhibits
gastric emptying.
Martinez V,et al. J Pharmacol
Exp Ther 2002 May;301(2):611-7
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