(Phe2,Orn8)-Oxytocin
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(Phe2,Orn8)-Oxytocin

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(Phe2,Orn8)-Oxytocin is a potent agonist of vasopressor (V1) with very little antidiuretic (V2) activity.

Category
Peptide Inhibitors
Catalog number
BAT-015175
CAS number
2480-41-3
Molecular Formula
C42H65N13O11S2
Molecular Weight
992.18
(Phe2,Orn8)-Oxytocin
IUPAC Name
(2S)-N-[(2S)-5-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-benzyl-13-[(2S)-butan-2-yl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide
Synonyms
(Phe2,Ile3,Orn8)-Vasopressin; L-cysteinyl-L-phenylalanyl-L-isoleucyl-L-glutaminyl-L-asparagyl-L-cysteinyl-L-prolyl-L-ornithyl-glycinamide (1->6)-disulfide; H-Cys-Phe-Ile-Gln-Asn-Cys-Pro-Orn-Gly-NH2 (Disulfide bridge: Cys1-Cys6); 1-({(4R,7S,10S,13S,16S,19R)-19-Amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-benzyl-13-[(2S)-2-butanyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}carbonyl)-L-prolyl-L-ornithylglycinamide
Appearance
White or Off-white Lyophilized Powder
Purity
95%
Density
1.337±0.1 g/cm3
Boiling Point
1536.7±65.0°C at 760 mmHg
Sequence
CFIQNCP-Orn-G-NH2 (Disulfide bridge: Cys1-Cys6)
Storage
Store at -20°C
Solubility
Soluble in Water
InChI
InChI=1S/C42H65N13O11S2/c1-3-22(2)34-41(65)50-26(13-14-31(45)56)37(61)52-28(18-32(46)57)38(62)53-29(21-68-67-20-24(44)35(59)51-27(39(63)54-34)17-23-9-5-4-6-10-23)42(66)55-16-8-12-30(55)40(64)49-25(11-7-15-43)36(60)48-19-33(47)58/h4-6,9-10,22,24-30,34H,3,7-8,11-21,43-44H2,1-2H3,(H2,45,56)(H2,46,57)(H2,47,58)(H,48,60)(H,49,64)(H,50,65)(H,51,59)(H,52,61)(H,53,62)(H,54,63)/t22-,24-,25-,26-,27-,28-,29-,30-,34-/m0/s1
InChI Key
DHMCDFJJCGVQSC-OVCMMVBBSA-N
Canonical SMILES
CCC(C)C1C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(C(=O)NC(C(=O)N1)CC2=CC=CC=C2)N)C(=O)N3CCCC3C(=O)NC(CCCN)C(=O)NCC(=O)N)CC(=O)N)CCC(=O)N
1. A V1-type receptor for mediating the neurohypophysial hormone-induced ACTH release in trout pituitary
P M Pierson, B Lahlou, M E Guibbolini J Endocrinol . 1996 Apr;149(1):109-15. doi: 10.1677/joe.0.1490109.
We analysed the effects of specific neurohypophysial analogues for pharmacological characterization of the type of vasotocin receptor involved in the control of the adrenocorticotrophin hormone (ACTH) release from the perifused pituitary in the rainbow trout, Oncorhynchus mykiss. Mammalian corticotrophin releasing factor (CRF) and teleostean neurohypophysial peptides (arginine vasotocin (AVT) and isotocin (IT)) stimulated ACTH release. Analysis of concentrations giving half-maximal effects (D50) showed that these peptides affected ACTH release in the following order of potency: CRF (8 x 10(-13) M) > AVT (2 x 10(-10) M) > IT (10(-7) M). Maximal responses (Dmax) were obtained for hormonal concentrations of 10(-10) M, 10(-8) M and 10(-6) M respectively. This suggests that AVT and IT have different roles in the control of ACTH release. The values obtained for AVT and IT were in agreement with the circulating levels we previously found for these peptides. Specific V1 or V2 agonists or antagonists (with reference to vasopressin in mammals) were used to define the specificity of the neurohypophysial peptide receptor involved in this stimulation. The V1 agonist, [Phe2, Orn8]-oxytocin, stimulated ACTH release while the V2 agonist, [deamino1, Val4, D-Arg8]-vasopressin, had no such effect. Maximal and half-maximal responses were obtained in the presence of the V1 agonist with 10(-7) M and 7 x 10(-9) M respectively, and were in the range of values obtained with natural peptides. The V1 antagonist, [d(CH2)5(1), O-Me-Tyr2, Arg8]-vasopressin, and the V2 antagonist, [d(CH2)5(1), D-Ile2, Ile4, Arg8, Ala9]-vasopressin, maximally reversed the 10(-9) M AVT-stimulated ACTH release by 60% and 25% respectively, for a 5 x 10(-10) M concentration of the analogues and a D50 approximately 2 x 10(-11) M. These results demonstrated the presence of only one V1-type receptor in fish pituitary, with some of the structural and functional peculiarities typically displayed by the mammalian V1a-type receptor, but distinct from it. In this sense, the fish pituitary vasotocin receptor may represent a novel type of neurohypophysial hormone receptor, more closely related to the mammalian V1b-type.
2. Role of V1 receptors in the action of vasopressin on the baroreflex control of heart rate
J Wong, L Chou, V Wong, I Ajaelo, J Luk, D Chang, I A Reid Am J Physiol . 1993 Sep;265(3 Pt 2):R524-9. doi: 10.1152/ajpregu.1993.265.3.R524.
Arginine vasopressin (AVP) elicits a larger decrease in heart rate for a given increase in arterial pressure than do other vasoconstrictors, but there is disagreement as to whether this results from an increase in baroreflex gain or a resetting of the baroreflex to a lower blood pressure. It is also unclear which type of vasopressin receptor mediates the action of vasopressin on the baroreflex. In the present study, the effects of vasopressin, selective vasopressin V1 and V2 receptor agonists, oxytocin, and a vasopressin V1 receptor antagonist on the baroreflex control of heart rate were investigated in conscious, chronically prepared rabbits. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside and analyzed using a four-parameter logistic model. Intravenous infusion of vasopressin at 5 ng.kg-1.min-1 increased mean arterial pressure by 9 mmHg and decreased heart rate by 31 beats/min. The arterial pressure at the midrange of the baroreflex curve (BP50) decreased from 75.9 +/- 4.8 to 57.6 +/- 1.7 mmHg (P < 0.01), indicating a shift of the baroreflex curve to a lower pressure, but the gain did not change significantly. The actions of vasopressin on blood pressure, heart rate, and BP50 were completely blocked by pretreatment with d(CH2)5[Tyr(Me)2]AVP, a selective V1 receptor antagonist. Infusion of [Phe2,Ile3,Orn8]AVP, a selective V1 receptor agonist, produced cardiovascular effects similar to those of vasopressin and decreased the BP50 of the baroreflex from 73.0 +/- 2.2 to 63.8 +/- 2.2 mmHg (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
3. Oxytocin and V1 vasopressin receptors in rabbit endometrium during pregnancy
V Guardabasso, M Serio, S Giannini, G Fantoni, M Maggi, A Peri J Reprod Fertil . 1991 Mar;91(2):575-81. doi: 10.1530/jrf.0.0910575.
Neurohypophysial hormone receptors were identified and characterized in rabbit endometrium and decidua by radioligand binding methods. The results strongly support the presence of a heterogeneity of sites in the decidua of parturient rabbits. The oxytocin site (R1) binds oxytocin and oxytocin analogues ([Thr4, Gly7]oxytocin and OTA) with high affinity, whereas the AVP site (R2) was selective for the V1 AVP analogues, [Phe2, Orn8]VT and d(CH2)5TyrMeAVP. The concentration of oxytocin receptors was low (50-100 fmol/mg protein) at oestrus (Day 0) and on Day 29 of pregnancy, but increased significantly (about 8-fold, P less than 0.05) during parturition. Conversely, V1 AVP receptors were more concentrated than the oxytocin sites at the end of pregnancy (150 fmol/mg protein) but did not change during parturition. These results indicate that neurohypophysial hormones have specific receptors not only in the myometrium but also in the uterine mucosa and we suggest that these receptors may participate in the regulation of uterine activity during pregnancy.
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