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Definition
The neurohypophysial hormone oxytocin (OT) was the first peptide hormone to have its structure determined and the first to be chemically synthesized in biologically active form. It is named after the “quick birth” which it causes due to its uterotonic activity. OT was also found to be responsible

for the milk-ejecting activity of the posterior pituitary gland 1.


Related Peptides
Vasopressin and OT are nonapeptides that are present in all placental mammals. Although similar in structure, they serve different functions. Peptides of the vasopressin family have a basic amino acid residue at position 8 in common, whereas OT and related peptides have a neutral amino acid residue at this position. The chemical nature of this amino acid residue is thought to be of critical importance in the interactions of the peptides with their respective receptors 2.


Analogs
It has been reported that the inhibitory properties of [2-0-methyltyrosine]-oxytocin (methyloxytocin) can be accentuated by additional substitution of the terminal amino group by a carbamoyl residue. While methyloxytocin acts as an inhibitor of OT on some assay systems and has an OT-like action on others, its N-carbamoyl derivative acts as an antagonist on all the systems which are generally used for the assay of oxytocin 3. Corey-Pauling-Koltun models of [Gly7] deaminooxytocin, deaminotocinamide, and their respective retro-D-analogs are essential for "occupation" and "activation" of uterine receptors4. The protracted effect of [2-O-methyltyrosine]-deamino-1-carba-oxytocin, [2-O-methyltyrosine]-oxytocin and its dimeric form  studied on the mammary gland of lactating rat in vivo showed a biphasic course of biological response that led to the assumption that the substances behaved like hormonogens5. Replacement of the amide groups of Gln(4) and Asn(5) in OT by tetrazole analogues of aspartic, glutamic and alpha-aminoadipic acids containing the tetrazole moiety in the side chains leads to analogues with decreased biological activities6. 1-Butanoic acid-2-(O-methyl-L-tyrosine)-1-carbaoxytocin (carbetocin) and/or other long-acting oxytocin analogues are formulated with a pharmaceutically acceptable carrier and administered in an amount sufficient to inhibit initiation or growth of breast cancer in the patient. The carbetocin and/or other long-acting OT analogues may also be formulated with a pharmaceutically acceptable carrier and administered in an amount sufficient to treat, prevent or alleviate the symptoms of a psychiatric disorder in the patient7, 8.


Discovery
OT and vasopressin were isolated and synthesized by Vincent du Vigneaud in 1953. The structure of the OT gene was elucidated in 1984, and the sequence of the OT receptor was reported in 1992 2.


Structural Characteristics
All neurohypophysial hormones are nonapeptides with a disulfide bridge between Cys residues 1 and 6. This results in a peptide constituted of a six-amino acid cyclic part and a COOH-terminal a-amidated three-residue tail. Based on the amino acid at position 8, these peptides are classified into vasopressin and OT families: the vasopressin family contains a basic amino acid (Lys, Arg), and the OT family contains a neutral amino acid at this position. Isoleucine in position 3 is essential for stimulating OT receptors and Arg or Lys in position 8 for acting on vasopressin receptors. The difference in the polarity of these amino acid residues is believed to enable the vasopressin and OT peptides to interact with the respective receptors 1.


Mode of Action
The OT receptor is a typical member of the rhodopsin-type (class I) GPCR family. The seven transmembrane a-helices are most highly conserved among the GPCR family members. Conserved residues among the GPCRs may be involved in a common mechanism for activation and signal transduction to the G protein. OT receptors are functionally coupled to Gq/11 a class GTP binding proteins that stimulate together with Gß? the activity of phospholipase C-ß isoforms. This leads to the generation of inositol trisphosphate and 1, 2-diacylglycerol. Inositol trisphosphate triggers Ca2+ release from intracellular stores, whereas diacylglycerol stimulates protein kinase C, which phosphorylates unidentified target proteins. Finally, in response to an increase of intracellular [Ca2+], a variety of cellular events are initiated.


Functions
Stimulation of milk ejection (milk letdown): Mammary alveoli are surrounded by smooth muscle (myoepithelial) cells which are a prominent target cell for OT. OT stimulates contraction of myoepithelial cells, causing milk to be ejected into the ducts and cisterns.

Stimulation of uterine smooth muscle contraction at birth: During the later stages of gestation, there is an increase in abundance of OT receptors on uterine smooth muscle cells, which is associated with increased "irritability" of the uterus (and sometimes the mother as well). OT is released during labor when the fetus stimulates the cervix and vagina, and it enhances contraction of uterine smooth muscle to facilitate parturition or birth.

In cases where uterine contractions are not sufficient to complete delivery, physicians and veterinarians sometimes administer OT (pitocin) to further stimulate uterine contractions.

Establishment of maternal behavior: During parturition, there is an increase in concentration of OT in cerebrospinal fluid, and OT acting within the brain plays a major role in establishing maternal behavior1.

References


1.     Gimpl  G,  Fahrenholz F (2001). The Oxytocin Receptor System:Structure, Function, and Regulation. Physiol Rev., 81(2):629-683.

2.     Van Kesteren RE, Smit AB, De Lange RP, Kits KS, Van Golen FA, Van Der Schors RC, De With ND, Burke JF, Geraerts WP (1995). Structural and Functional Evolution of the Vasopressin/Oxytocin Superfamily: Vasopressin-Related Conopressin Is the Only Member Present in Lymnaea, and Is Involved in the Control of Sexual Behavior. J  Neurosci., 15(9): 5989-5998.

3.     Bisset GW, Clark BJ,  Krejci I, Polacek I,  Rudinger J (1970). Some pharmacological properties of a synthetic oxytocin analogue 11-N-carbamoyl-hemicystine-2-0-methyltyrosinel-oxytocin (carbamoylmethyloxytocin), an antagonist to the neurohypophysial hormones. Br. J. Plarinac., 40: 342-360.

4.     Hechter O, Kato T, Nakagawa SH, Yang F, Flouret G (1975). Contribution of the Peptide Backbone to the Action of Oxytocin Analogs (stereoisomers/hormone action). PNAS., 72(2):563-566.

5.     Barth T, Flegel M, Jost K (1976. Protracted milk-ejecting effect of some oxytocin analogues in rats. Endocrinol Exp., 10(1):65-71.

6.     Manturewicz M, Grzonka Z, Borovicková L, and Slaninová J (2007). Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9. Acta biochimica Polonica, 54(4):805.

7.     Cassoni P, Sapino A, Papotti M, Bussolati G(1996). “Oxytocin and Oxytocin-Analogue F314 Inhibit cell Proliferation and Tumor Growth of Rat and Mouse mammary carcinomas,” Int. J. Cancer., 66(6):817-820.

8.     Cassoni P, Sapino A, Fortunati N, Munaron L, Chini B, Bussolati G (1997). “Oxytocin Inhibits the Proliferation of MDA-MB231 Human Breast-Cancer Cells Via Cyclic Adenosine Monophosphate and Protein Kinase A,” Int. J. Cancer., 72:340-344.

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If you are unable to find your desired product please contact us for assistance or send an email to info@biosyn.com

 
Product Name Catalog # Unit Price/Unit 
3,4 Dehydro - Pro - Arg - Vasotocin
CYIQNC(3,4-Dehydro-pro)-RG-CONH2 (S-S Bond)
12807-01 1 mg $350 cart inquire
Aquaporin - 2 (254 - 267), human
RQSVELHSPQSLPR
12802-01 1 mg $220 cart inquire
Aquaporin - 2 (254 - 267), pSER256, human
RQ-pS-VELHSPQSLPR
12803-01 1 mg $255 cart inquire
Aquaporin - 2 (255 - 271), human
QSVELHSPQSLPRGSKA
12804-01 1 mg $235 cart inquire
Aquaporin - 2 (255 - 271), rat
QSVELHSPQSLPRGTKA
12805-01 1 mg $235 cart inquire
[Arg8] - Vasopressin (AVP)
CYFQNCPRG-CONH2 (Disulfide bridge: 1-6)
12799-01 1 mg $210 cart inquire
[Arg8] - Vasopressin (AVP)
CYFQNCPRG-CONH2 (Disulfide bridge: 1-6)
12799-05 5 mg $122 cart inquire
[Arg8] - Vasopressin, free acid
CYFQNCPRG (Disulfide bridge: 1-6)
12800-01 1 mg $240 cart inquire
Biotin - Oxytocin
Biotin-CYIQNCPLG-CONH2 (Disulfide bridge: 1-6)
12797-01 1 mg $198 cart inquire
Oxytocin
CYIQNCPLG-CONH2 (Disulfide bridge: 1-6)
12798-05 5 mg $120 cart inquire
Oxytocin
CYIQNCPLG-CONH2 (Disulfide bridge: 1-6)
12798-25 25 mg $286 cart inquire
Serum Albumin (102 - 226)
ADDKETCFAEEGKKLVAASQAALGL
12808-01 1 mg $330 cart inquire

Biosynthesis Inc.