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predominately involved in the modulation and inhibition of action potentials in neurons



schematics galanin human


schematics galanin rat

schematics galanin porcine


schematics galanin bovine

 

 

sequence comparison galanin
Galanin is a neuropeptide with a wide variety of biological functions, including that of a strong endogenous anticonvulsant. No nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin, a combinatorial library was designed, synthesized, and screened at the rat hippocampal galanin receptor. A low molecular weight galanin receptor agonist, 7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin (galnon) was found to displace (125)I-galanin with micromolar affinity at Bowes cellular and rat hippocampal membranes. Autoradiographic binding assay on rat spinal cord sections confirmed the ability of galnon to displace (125)I-galanin from its binding sites. Galnon inhibited adenylate cyclase activity, suggesting an agonist action at galanin receptors. When injected i.p. galnon reduced the severity and increased the latency of pentylenetetrazole-induced seizures in mice and reversed the proconvulsant effects of the galanin receptor antagonist M35, injected into a lateral ventricle. Intrahippocampal injection of galnon also shortened the duration of self-sustaining status epilepticus in rats, confirming its agonist properties in vivo. Pretreatment of rats with antisense peptide nucleic acid targeted to galanin receptor type 1 mRNA abolished the effect of galnon, suggesting mediation of its anticonvulsant properties through this receptor subtype. These findings introduce a systemically active nonpeptide galanin agonist anticonvulsant.

Saar K, Mazarati AM, Mahlapuu R, et al. Anticonvulsant activity of a nonpeptide galanin receptor agonist. Proc Natl Acad Sci USA. 2002;99(10):7136-41.

Galanin is a widely distributed neuropeptide with a variety of physiological functions. Three galanin receptor subtypes, GALR1, GALR2, and GALR3, have been reported. We isolated a novel galanin-like peptide (GALP) from porcine hypothalamus by observing its activity for increasing [(35)S]GTPgammaS binding to a membrane preparation of GALR2-transfected cells. The peptide had 60 amino acid residues and a non-amidated C terminus. The amino acid sequence of GALP-(9-21) was completely identical to that of galanin-(1-13). A cloned porcine GALP cDNA indicated that GALP was processed from a 120-amino acid GALP precursor protein. The structures of rat and human GALP-(1-60) were deduced from cloned cDNA, which indicated that the amino acid sequences 1-24 and 41-53 were highly conserved between humans, rats, and pigs. Receptor binding studies revealed that porcine GALP-(1-60) had a high affinity for the GALR2 receptor (IC(50) = 0.24 nM) and a lower affinity for the GALR1 receptor (IC(50) = 4.3 nM). In contrast, galanin showed high affinity for the GALR1 (IC(50) = 0.097 nM) and GALR2 receptors (IC(50) = 0.48 nM). GALP is therefore an endogenous ligand that preferentially binds the GALR2 receptor, whereas galanin is relatively non-selective.

Ohtaki T, Kumano S, Ishibashi Y, et al. Isolation and cDNA cloning of a novel galanin-like peptide (GALP) from porcine hypothalamus. J Biol Chem. 1999;274(52):37041-5.

The galanin neuropeptide system is widely distributed throughout the brain and periphery and is thought to play a role in feeding, pain and reproduction. To evaluate the human galanin receptor 1 as a potential therapeutic target, we fully characterized its interaction with several galanin-like peptides. The human galanin receptor 1 receptor was stably expressed using an episomal system in human embryonic kidney 293E cells. Saturation isotherms using 125I-human galanin revealed two distinct populations of receptor affinity states in membranes and whole cells with picomolar and nanomolar affinities at the high- and low affinity states, respectively. A scintillation proximity assay revealed that 125I-human galanin binding in membranes reached steady-state within 2 to 2.5 hr; however, only 50% of galanin radiolabel dissociated from the receptors by excess galanin or guanosine 5'-O-3-thiotriphosphate even after 20 hr. In contrast, galanin binding in whole cells was completely reversible within 1 hr. Competition binding assays showed that galanin-like peptides bound with picomolar affinities in membranes and whole cells. These peptides behaved as full agonists as determined by the inhibition of forskolin-stimulated cyclic 3'5'-adenosine monophosphate production and the stimulation of guanosine 5'-O-(3-[35S]thiotriphosphate binding. The agonist profile of M40, a representative chimeric peptide, was found not to be the result of receptor reserve because receptor inactivation by partial alkylation experiments confirmed its full intrinsic efficacy under conditions of a "zero" reserve state. These observations suggest that the antagonist effects in vivo of M40, and perhaps other chimeric peptides, are not mediated via direct interactions with the galanin receptor 1 receptor.

Fitzgerald LW, Patterson JP, Conklin DS, Horlick R, Largent BL. Pharmacological and biochemical characterization of a recombinant human galanin GALR1 receptor: agonist character of chimeric galanin peptides. J Pharmacol Exp Ther. 1998;287(2):448-56.

Obesity Related Peptide

 

    

Peptide Name

Function

Tracer

Tissue or cell 

 

References

galantide (M15), galanin-(1-12) -Pro-SP-(5-11) amide

antagonist

 

rat hypothalamus

KD(1) less than 0.1 nM and KD(2) approximately 6 nM

Langel U, et al. Int J Pept Protein Res. 1992 ; 39(6) :516-22

galanin 

agonist

[125I] Galanin

rat pancreatic beta-cell line Rin m 5F

KD: 1 nM

Kask K, et al. Regul Pept. 1995 , 59(3):341-8

galanin-(1-16)

agonist

[125I] galanin

rat forebrain and spinal cord

IC50: 3 nM

Fisone G, et al. Proc Natl Acad Sci U S A. 1989; 86(23) :9588-91

M35 [galanin(1-13)- bradykinin (2-9) amide]

antagonist
agonist ?

[125I] M35

rat pancreatic beta-cell line Rin m 5F

KD = 0.9 +/- 0.1 nM; Bmax=72 +/- 3 fmol/mg protein

Kask K, et al. Regul Pept. 1995, 59(3) :341-8

M15 (galantide)

antagonist

 

 

Hill coefficient:0.4-0.5

Ogren SO, et al. Eur J Pharmacol. 1993;242(1):59-64

Galnon

non-peptide agonist

 

spinal cord membranes

KD:6+/-0.6 microM

Wu WP, et al. Eur J Pharmacol. 2003 ;482(1-3):133-7

 M242

 

 

Bowes cells& Chinese hamster ovary cells

at hGalR1<1 nM and at hGalR2<10 nM

Saar K, et al. Regul Pept. 2001; 102(1) :15-9

M38, [galanin(1-13)- (Ala-Leu)3-Ala amide]

antagonist

 

 

 

Xu XJ, et al. Br J Pharmacol. 1995 Oct;116(3):2076-80

M40, [galanin(1-13) -Pro-Pro-(Ala-Leu)2-Ala amide]

antagonist in vivo

 

 

 

Xu XJ, et al. Br J Pharmacol. 1995 Oct;116(3):2076-80

C7 [galanin (1-13)-spantide] 11

antagonist

 

 

 

Xu XJ, et al. Br J Pharmacol. 1995 Oct;116(3):2076-80

Galanin (Porcine)

agonist

[125I]galanin (porcine)

Bowes melanoma cell line

KD = 0.05 +/- 0.01 nM; Bmax = 135 +/- 7 fmol/mg protein

Heuillet E, et al. Eur J Pharmacol. 1994 ; 269 (2):139-47

Galanin (Human)

agonist

[125I]galanin (porcine)

Bowes melanoma cell line

IC50 = 0.35 +/- 0.13 nM

Heuillet E, et al. Eur J Pharmacol. 1994 ; 269 (2):139-47

    

 


Related Products

Catalog# Product Standard Size Price
026-52 Galanin-Like Peptide (GALP) (Rat) 100 µg $214
026-13 Galanin (Rat, Mouse) 200 µg $138
026-16 Galanin (1-13)-Bradykinin (2-9) amide / M35 200 µg $56
026-17 Galanin (1-13)-Pro-Pro-(Ala-Leu)2-Ala amide / M40 200 µg $66
026-18 Galanin (1-13)-Spantide amide / C7 200 µg $87
026-08 Galanin (1-16) (Rat, Porcine) 200 µg $43
026-02 Galanin (1-19) (Human) 200 µg $77
026-03 Galanin (1-30) (Human) 200 µg $199
026-21 Galanin (2-11) amide / AR-M1896 (Human) 200 µg $107
026-04 Galanin (65-88) (Human) 200 µg $97
026-05 Galanin (89-123) (Human) 200 µg $214
026-19 Galanin (Bovine) 200 µg $138
026-01 Galanin (Human) 200 µg $128
H-026-01 Galanin (Human) - Antibody 50 µl $179
FG-026-01A Galanin (Human) - FAM Labeled 1 nmol $357
T-026-01 Galanin (Human) - I-125 Labeled 10 µCi $723
T-G-026-01 Galanin (Human) - I-125 Labeled Purified IgG 10 µCi $723
MB-026-01 Galanin (Human) - MagBead (Magnetic Bead Linked Antibody) 1 ml $638
MRK-026-01 Galanin (Human) - Magnetic Bead RIA Kit 125 tubes $671
G-026-01 Galanin (Human) - Purified IgG Antibody 400 µg $332
RK-026-01 Galanin (Human) - RIA Kit 125 tubes $588
FR-026-01 Galanin (Human) - Rhodamine Labeled 1 nmol $357
026-06 Galanin (Porcine) 200 µg $138
H-026-06 Galanin (Porcine) - Antibody 50 µl $179
T-026-06 Galanin (Porcine) - I-125 Labeled 10 µCi $723
T-G-026-06 Galanin (Porcine) - I-125 Labeled Purified IgG 10 µCi $723
G-026-06 Galanin (Porcine) - Purified IgG Antibody 400 µg $332
RK-026-06 Galanin (Porcine) - RIA Kit 125 tubes $588
H-026-13 Galanin (Rat, Mouse) - Antibody 50 µl $179
FG-026-13A Galanin (Rat, Mouse) - FAM Labeled 1 nmol $357

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