PACAP-27 (human, mouse, ovine, porcine, rat) trifluoroacetate salt

Names

[ Name ]:
PACAP-27 (human, mouse, ovine, porcine, rat) trifluoroacetate salt

[Synonym ]:
MFCD00167418
L-Leucinamide, L-histidyl-L-seryl-L-α-aspartylglycyl-L-isoleucyl-L-phenylalanyl-L-threonyl-L-α-aspartyl-L-seryl-L-tyrosyl-L-seryl-L-arginyl-L-tyrosyl-L-arginyl-L-lysyl-L-glutaminyl-L-methionyl -L-alanyl-L-valyl-L-lysyl-L-lysyl-L-tyrosyl-L-leucyl-L-alanyl-L-alanyl-L-valyl-
ADENYLATE CYCLASE ACTIVATING PEPTIDE-27
L-Histidyl-L-seryl-L-α-aspartylglycyl-L-isoleucyl-L-phenylalanyl-L-threonyl-L-α-aspartyl-L-seryl-L-tyrosyl-L-seryl-L-arginyl-L-tyrosyl-L-arginyl-L-lysyl-L-glutaminyl-L-methionyl-L-alanyl-L-val yl-L-lysyl-L-lysyl-L-tyrosyl-L-leucyl-L-alanyl-L-alanyl-L-valyl-L-leucinamide
Talopram hydrochloride
PACAP (1-27), human, ovine, rat

Biological Activity

[Description]:

PACAP (1-27), human, ovine, rat, the N-terminal fragment of PACAP-38, is a potent PACAP receptor antagonist with IC50s of 3, 2, and 5 nM, respectively, for rat PAC1, rat VPAC1, and human VPAC2.

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

Peptides

[Target]

IC50: 3 nM (rat PAC1), 2 nM (rat VPAC1), 5 nM (human VPAC2)[1]

[In Vitro]

The PACAP type I and II receptors recognize PACAP-27 and PACAP-38 with an equal high affinity[1]. PACAP(1-27) exhibits a distinct and much higher susceptibility to VIP-amino acid substitutions, compared to PACAP (1-38). Positions 4 and 5 seem to be most important for receptor binding of PACAP (1-27), whereas position 13 is identified to be crucial for maximal affinity of PACAP (1-38)[2].

[In Vivo]

PACAP (1-27) produces significant bronchodilatation and rapid onset of sustained action and without pronounced cardiovascular side effects. This peptide may have therapeutic potential as a bronchodilator[3]. PACAP(1-27) (0.005-5 μg) increases the basal insulin secretion by about 15 folds in a dose-dependent manner. Local infusion of either glucose (5%) or PACAP(1-27) (0.05 μg) results in a significant increase in the basal insulin output to about 300 μUx per min per g. PACAP(1-27) directly enhances the glucose-evoked insulin secretion in the endocrine pancreas in anesthetized dogs. The study suggests that PACAP may play a local facilitating role in insulin secretion in response to glucose loading[4].

[Animal admin]

Guinea-pigs[3] PACAP-27 (0.045 to 4.5 nmol/kg/min), salbutamol (0.045 to 4.5 nmol/kg/min) or sterile saline is given i.v. (1.0 mL) via an infusion pump, starting 5 min before and continuing 10 min after airway challenge[3]. Dogs[4] Four dogs (28.4±1.8 kg) receive PACAP (1-27) with four different concentrations of 0.01, 0.1, 1.0 and 10 µg/mL, or 0.00318, 0.0318, 0.318 and 3.18 µM, respectively. Each solution is locally infused at a rate of 0.5 mL/min for precisely 1 min. A total dose delivered to the pancreas during each infusion is therefore 0.005, 0.05, 0.5 and 5 µg. The dead volume of the pancreatic arterial catheter (0.5 mL) is taken into account in relation to the infusion rate. After taking the initial control sample, simultaneously from the SPD vein and the aorta, saline is infused for 1 min and samples are obtained 1, 3 and 5 min after the onset of infusion. This procedure is repeated every 15 min for the doses of PACAP (1-27). The sample obtained at 15 min after the onset of each infusion served as control for the subsequent intervention[4].

[References]

[1]. Gourlet P, et al. Fragments of pituitary adenylate cyclase activating polypeptide discriminate between type I and II recombinant receptors. Eur J Pharmacol. 1995 Dec 4;287(1):7-11.

[2]. Schäfer H, et al. Structural motifs of pituitary adenylate cyclase-activating polypeptide (PACAP) defining PAC1-receptor selectivity. Regul Pept. 1999 Feb 5;79(2-3):83-92.

[3]. Lindén A, et al. Inhibition of bronchoconstriction by pituitary adenylate cyclase activating polypeptide (PACAP 1-27) in guinea-pigs in vivo.

[4]. Yamaguchi N, et al. Pituitary adenylate cyclase activating polypeptide enhances glucose-evoked insulin secretion in the canine pancreas in vivo. JOP. 2001 Sep;2(5):306-16.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Molecular Formula ]:
C₁₄₂H₂₂₄N₄₀O₃₉S

[ Molecular Weight ]:
3147.608

[ Exact Mass ]:
3145.649414

[ PSA ]:
1340.85000

[ LogP ]:
-3.65

[ Appearance of Characters ]:
solid | white

[ Index of Refraction ]:
1.657

[ Storage condition ]:
−20°C

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

Articles

PACAP system evolution and its role in melanophore function in teleost fish skin.

Mol. Cell. Endocrinol. 411 , 130-45, (2015)

Pituitary adenylate cyclase-activating polypeptide (PACAP) administered to tilapia melanophores ex-vivo causes significant pigment aggregation and this is a newly identified function for this peptide ...

Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet beta-cells.

J. Biol. Chem. 269 , 1290-1293, (1994)

Insulin secretion from pancreatic islets is controlled by peptides as well as by nutrients. We report here a novel, extraordinarily potent peptidergic regulation of insulin secretion. A 27-residue for...

Pituitary adenylate cyclase-activating polypeptide increases [Ca2]i in rat gonadotrophs through an inositol trisphosphate-dependent mechanism.

J. Biol. Chem. 269 , 5680, (1994)

Pituitary adenylate cyclase-activating polypeptide (PACAP) increases cAMP production and stimulates hormone release from a variety of anterior pituitary cells. However, in anterior pituitary gonadotro...