CGRP
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Receptor Activity Modifying Proteins (RAMPs) and Calcitonin Receptor Like Receptor (CRLR)  

 

The calcitonin family of bioactive peptides comprises of calcitonin, amylin, two calcitonin-gene related peptides (CGRP1, and CGRP2) and adrenomedullin (ADM). Calcitonin is 32 aa peptide found in the parafollicular "C" cells of the thyroid in mammals. It is also found in a number of non-mammals. It regulated the mineral (calcium and phosphate) balance. Calcitonin causes hypercalcemia by acting as an inhibitor of osteoclast induced bone resorption. CGRP is a 37-aa peptide produced by tissue specific processing of the calcitonin gene. Calcitonin is the major product in the thyroid, whereas CGRP is the major product in neural tissues. CGRP is a potent cardiovascular agent. It has structural similarity with amylin. CGRP is found in two isoforms (CGRP-I and CGRP-II) that differs only by 3 amino acids.

Amylin is a 37-aa peptide produced in the pancreatic beta-cell secretory granules and is co-released with insulin. Amylin also has CGRP-like effects on bone metabolism. Amylin has specific binding sites in the CNS and it may regulate gastric emptying and influence carbohydrate metabolism.

Adrenomedullin (ADM) is a 52-aa hypotensive peptide. It has structural similarity with CGRP and amylin. ADM is produced in peripheral tissues, adrenal medulla, lung, and kidney. ADM has specific receptors on astrocytes and it is unregulated in ischaemia. In general, calcitonin family of peptides has N-terminal ring structures of 6-7 aa involving a disulfide and an amidated C-terminal end.

The calcitonin family peptides probably act through G-protein coupled membrane receptors. The gene for calcitonin receptors has been cloned. It is homologous to GPCRs in family "B" which typically recognizes regulatory peptides (secretin, glucagons, VIP). Recently, a homolog of calcitonin receptor, CRLR (calcitonin-receptor-like receptor human 461 aa; rat/mouse 463 aa) was identified. CRLR has 55% homology with calcitonin receptor. Other members of calcitonin peptide family were candidate for CRLR but CRLR seemed not to be a receptor for CGRP. Two related members of the family "A" class of GPCR, RDC1 and G10D, were then identified as receptors for CGRP and ADM, respectively. It is now shown that CRLR can function as either a CGRP receptor or an ADM receptor, depending upon which members of a new family of proteins called receptor activity modifying proteins (RAMP1-3) are expressed. RAMPs1-3 contains an N-terminal signal peptide, an extracellular N-terminus, a single transmembrane domain near the C-terminus, and cytoplasmic C-terminus. RAMP1-3 displays 31% identity. RAMPS may be involved in the transport of CRLR to the plasma membrane. RAMP1 (human, mouse, rat 148 aa) presents the CRLR receptor as a glycoprotein that functions as CGRP receptor. RAMP1 is expressed in many tissues, including the uterus, bladder, brain, pancreas, and GI tract. CRLR and RAMP1 are not co-expressed in all tissues suggesting that their co-expression may define which cells express functional CGRP receptors. RAMP2 (human 175 aa; rat 182 aa, and mouse 189 aa)-transported receptors are core-glycosylated and function as ADM receptor. It is expressed in the lung, breast, immune system and fetal tissues. RAMP3 is most abundant in the kidney and lung.

 

 Items

Antigen peptide location 

 Antibody Host

* Expected  Ab Crossreactivity

 Neat Antisera Cat # 100 ul

Aff. Pure IgG or Mab
(100 ug)

 * Control Peptide
(100 ug)

RAMP1

H, 19 aa ~I,
H, 11 aa, ~CT

Rb, poly

H, R, M

RAMP11-S

RAMP11-A 

RAMP11-P

RAMP2

H, 20 aa ~NT,
H, 9 aa, ~CT

Rb, poly

H, R, M

RAMP21-S

RAMP21-A

RAMP21-P

RAMP3

H, 13 aa ~I
H, 9 aa, ~CT

Rb, poly

H, R, M

RAMP31-S

RAMP31-A

RAMP31-P

RCP

 H, 18aa,
~NT

 Rb, poly

 H, R, M, C

RCP11-S

RCP11-A

RCP11-P

CRLR

 R, 20 aa
~CT

 Rb, poly

  R, M, H

CRLR11-S

CRLR11-A

CRLR11-P

 

 CGRP
(ab # 1)

 

 H, 19 aa,
~NT

 

 Rb, poly

 

 R, M, H

 

 CGRP11-S

 

CGRP11-A

 

CGRP11-P

 

 CGRP
(ab # 2)

 

 H, 14 aa,
~I

 

 Rb, poly

 

 R, M, H

 

 CGRP12-S

 

CGRP12-A

 

CGRP12-P

 

CGRP 1-37 aa (full length)

 

Human CGRP (1-37 aa, oxidized); Cat # CGRP15-P5; 500 ug
Rat CGRP (1-37 aa, oxidized); Cat # CGRP16-P5; 500 ug

 

CGRP II (1-37 aa)

 

 Human CGRP II (1-37 aa, oxidized); Cat # CGRP25-P5; 500 ug
Rat CGRP II (1-37 aa, oxidized); Cat # CGRP26-P5; 500 ug

 

 Amylin (ab # 1)

 

 H, 1-37aa

 

 Rb, poly

 

 R, M, H

 

 AMYL11-S

 

 

 AMYL11-P

 

  Human Amylin, 1-37aa
(Non-oxidized)

Amylin (1-37 aa, non-oxidized); Cat # AMYL14-P; 100 ug
Biotinylated-Amylin (1-37 aa, non-oxidized), Cat #AMYL15-P-100;100ug

 

Amylin, 1-37aa
(oxidized, Cys2-Cys7)

Human Amylin (1-37 aa, oxidized); Cat # AMYL16-P5; 500 ug
Rat Amylin (1-37 aa, oxidized); Cat # AMYL17-P5; 500 ug

 

 Amylin
(ab # 2)

 

H, 13 aa, ~I &
R 13 aa, ~I

 

 Rb, poly

 

 R, M, H

 

 AMYL12-S

 

 AMYL12-A

 

 AMYL12-P

 

 ADML

 H, 17 aa, ~CT

 

 Rb, poly

 

 R, M, H

 

 ADML11-S

 

 ADML11-A

 

 ADML11-P

 

Human ADML 1-52 aa (full length)

 

Human ADML 1-52 aa purified (>99%), Cat # ADM15-P; 100 ug

Control IgGs For use as -ve controls in ELISA, Western, IHC.

 

Control Mouse IgG (non immune), Cat # 20008-1 (1 mg)  
Control Rabbit IgG (non immune) , Cat # 20009-1 (1 mg)



M= Mouse; R=Rat; H=Human; Ha=Hamster; Rb=Rabbit; B=Bovine; C=Chicken; D=DOG; CT= near C-terminus; NT=near N-terminus; I=Middle of protein; CL=Cytoplasmic loop; EC=Extracellular domain; IC=Intracellular domain.

* Expected antibody crossreactivity information is mostly based upon high (>70%) sequence conservation of antigenic/control peptides in various species. When antibody crossreactivity has actually been experimentally confirmed in various species, it will be mentioned in the appropriate data sheets.

"Neat Antisera or antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" IgG may be more suitable for immunohistochemical (IHC) applications and to reduce background in most immunological applications including ELISA and Western.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody blocking studies to establish antibody specificity.
Western blot +ve protein controls, where available, are semi-pure, pure or recombinant proteins that are formulated in SDS-PAGE sample buffer (reduced). They are recommended to be used for Western (load 10 ul/lane) for visualization with antibodies.