Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The changes in FMRFamide (Phe-Met-Arg-Phe-NH2) immunoreactivity in response to incubation in dopamine, serotonin, met-enkephalin, oxytocin, arg-vasopressin and FMRFamide were examined in the central nervous system of the snail, Achatina fulica. 2. When the central nervous system was cultured in medium which contained dopamine and in medium which contained serotonin, the number of immunoreactive neurons increased in the anterior part of the cerebral ganglion and decreased in the sub-esophageal ganglion. 3. When arg-vasopressin was added to the culture medium, the number of immunoreactive neurons increased in the pedal ganglion and decreased in the other sub-esophageal ganglion. 4. By contrast, when the central nervous system was cultured in medium which contained oxytocin, the number of immunoreactive neurons did not increase, but rather decreased, in each ganglion. 5. No changes in immunoreactivity were detected in the central nervous system when it was cultured in medium which contained FMRFamide. 6. It appears, from these results, that the production and release of FMRFamide from different neurons are differentially affected by the physiologically active substances tested.
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PMID:Dynamics of FMRFamide immunoreactivity in response to physiologically active substances in the central nervous system of the snail, Achatina fulica. 290 40

The pairing of the 14 half-cystine residues of bovine neurophysin was established by sequential proteolytic digestion. Purified released peptides and the residual disulfide-linked core were monitored at each step by use of amino acid analysis, gas-phase sequencing, and mass spectrometry. The approach included application of gas-phase sequencing to assign disulfide pairs in peptides containing multiple disulfides. The results demonstrate that neurophysin disulfides are paired in two distinct domains--an NH2 domain (residues 10-54) containing four disulfides and a COOH domain (residues 61-85) containing three disulfides. The specific disulfide bridges are Cys-10 to Cys-54, Cys-13 to Cys-27, Cys-21 to Cys-44, Cys-28 to Cys-34, Cys-61 to Cys-73, Cys-74 to Cys-79, and Cys-67 to Cys-85. The results place the internally duplicated segments of neurophysin (residues 12-31 and 60-77) in separate domains. Disulfide-pairing patterns within each domain are homologous with the exception of the Cys-10 to Cys-54 bond, which is unique to the NH2 domain and which links the two ends of this domain together. The potential role of the Cys-10 to Cys-54 bond in organizing the hormone-binding site is discussed.
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PMID:Complete assignment of neurophysin disulfides indicates pairing in two separate domains. 291 88

We describe the synthesis and some pharmacological properties of 16 new in vivo antagonists of oxytocin. These are based on modifications of three peptides: A, B, and C. A is our previously reported potent and selective antagonist of the vasopressor (V1 receptor) responses to arginine-vasopressin (AVP)/weak oxytocin antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid), 2-O-methyltyrosine]arginine-vasopressin (d(CH2)5[Tyr(Me)2]AVP. B reported here, the Ile3 analogue of A, is d(CH2)5[Tyr(Me)2]AVT (5 below) and C is our previously reported potent nonselective oxytocin antagonist/AVP V1 antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O- methyltyrosine,8-ornithine]vasotocin (d(CH2)5[Tyr(Me)2]OVT). The following substitutions and deletions, alone or in combination, were employed in A, B, and C: 1-deaminopenicillamine (dP); D-Tyr(Alk)2 (where Alk = Me or Et), D-Phe2; Val4, Thr4; delta 3-Pro7; Lys8, Cit8; desGly9, desGly-NH2(9), Ala-NH2(9); Leu-NH2(9); Arg-NH2(9). The 16 new analogues are (1) d(CH2)5[D-Tyr(Me)2]AVP, (2) d(CH2)5[D-Tyr(Me)2, Val4,delta 3-Pro7]AVP, (3) d(CH2)5[D-Tyr-(Et)2, Val4,Lys8]VP, (4) d(CH2)5[D-Tyr(Et)2,Val4,Cit8]VP, (5) d(CH2)5[Tyr(Me)2]AVT, (6) d(CH2)5[Tyr(Me)2,Lys8]VT, (7) dP[Tyr(Me)2]AVT, (8) dP[Tyr(Me)2,Val4]AVT, (9) d(CH2)5[D-Tyr(Me)2, Val4]AVT, (10) d(CH2)5[D-Phe2,Val4]AVT, (11) d(CH2)5[Tyr(Me)2,Thr4]OVT, (12) d(CH2)5[Tyr(Me)2,Thr4,Ala-NH2(9)]OVT, (13) d(CH2)5[Tyr(Me)2,Thr4,Leu-NH2(9)]OVT, (14) d(CH2)5[Tyr(Me)2,Thr4,Arg-NH2(9)]OVT, (15) desGly-NH2(9),d(CH2)5[Tyr(Me)2,Thr4]OVT, (16) desGly9,d(CH2)5[Tyr(Me)2,Thr4]OVT. 1-4 are analogues of A, 5-10 are analogues of B, and 11-16 are analogues of C. Their protected precursors were synthesized either entirely by the solid-phase method or by a combination of solid-phase and solution methods (1 + 8 or 8 + 1 couplings). All analogues were tested in rats for agonistic and antagonistic activities in oxytocic (in vitro, without and with Mg2+, and in vivo) assays as well as by antidiuretic and vasopressor assays. All analogues exhibit potent oxytocic antagonism in vitro and in vivo. With an in vitro pA2 (in the absence of Mg2+) = 9.12 +/- 0.09, dP[Tyr(Me)2]AVT is (7) one of the most potent in vitro oxytocin antagonists reported to date. Fifteen of these analogues (all but 6) appear as potent or more potent in vivo oxytocin antagonists than C (pA2 = 7.37 +/- 0.17). Analogues 1-9 and 14 are potent AVP V1 antagonists. Their anti-V1 pA2 values range from 7.92 to 8.45. They are thus nonselective oxytocin antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Solid-phase synthesis of 16 potent (selective and nonselective) in vivo antagonists of oxytocin. 291 98

We have previously demonstrated that intracerebroventricular (ICV) administration of oxytocin (OXY) enhanced grooming behaviors in male and female rats at a 1 microgram dose. In the present study female rats were injected ICV with 1 microgram OXY or equimolar doses of other peptides. At this dose arginine-vasopressin (AVP), arginine-vasotocin (AVT) and lysine-vasopressin (LVP), as well as alpha-MSH, were as effective as OXY in increasing grooming behavior. At equimolar doses, ACTH1-10, tocinoic acid (the ring structure of OXY) and Pro-Leu-Gly-NH2 (the tail structure of OXY) had no significant effect on grooming behavior. The potency of AVP and AVT was determined across a 0.05-5 microgram dose range. Grooming scores increased in an apparent linear manner across a similar OXY dose range. Both AVP and AVT, however, manifested an inverted U grooming response curve. Maximum grooming scores resulted from a 0.1 microgram dose of AVT or a 0.5 microgram AVP dose. Analyses of the aspects of grooming separately found that nonapeptides OXY, AVP and AVT all elevated body grooming, washing, and scratching. Because AVT and AVP administration resulted in grooming scores significantly higher than OXY at lower doses, we concluded that the CNS is more sensitive to the effects of AVT and AVP on grooming behavior than OXY.
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PMID:A comparison of grooming behavior potencies of neurohypophyseal nonapeptides. 301 15

Peptides with vasopressin- and oxytocin-immunoreactivity were purified from bovine pineal glands. Three immunoreactive peptides were purified by successive high performance liquid chromatography steps in sufficient quantities for identification by fast atom bombardment-mass spectrometry. Two peptides were characterized as authentic vasopressin and oxytocin. Their identities were in agreement with the observed immunoreactivities, high performance liquid chromatography behavior, and biological activity. The third peptide was identified as N alpha-acetyloxytocin. The presence of the acetyl group was demonstrated by the molecular mass of the peptide, and the N alpha position was shown to be the modified site by the presence of a blocked NH2 terminus. N alpha-Acetylation of oxytocin may be involved in altering the biological properties of the peptide.
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PMID:Isolation and identification of vasopressin- and oxytocin-immunoreactive substances from bovine pineal gland. Presence of N alpha-acetyloxytocin. 312 16

Brain and spinal sites of action of the stable thyrotropin-releasing hormone (TRH) analogue, RX 77368 [pGlu-His-(3,3'-dimethyl)-Pro-NH2], for stimulation of gastric acid secretion have been investigated in urethane-anesthetized rats with gastric fistula. RX 77368 microinjected at a 7.7-pmol dose into the dorsal vagal complex or nucleus ambiguus stimulated gastric acid secretion to 62.2 +/- 15.9 and 45.3 +/- 14.3 mumol/h, respectively, whereas in the vehicle-treated group acid secretion was 0.5 +/- 1.0 mumol/h. A 10-fold higher dose of RX 77368 was inefficient when microinjected into the medial septum, central amygdala, or lateral hypothalamus. The gastric secretory response to microinjection of RX 77368 into the nucleus ambiguus was dose related (0.7-77 pmol), long-lasting (greater than 90 min), and blocked by vagotomy. TRH (144 pmol) injected into the nucleus ambiguus also stimulated gastric acid secretion but was less potent than the stable TRH analogue, whereas the unrelated peptide, oxytocin, was inactive. Intrathecal injection of RX 77368 at doses up to 2500 pmol did not modify gastric acid secretion. These results demonstrate that the dorsal vagal complex and nucleus ambiguus are TRH sites of action for stimulation of gastric acid secretion through vagal dependent pathways. These findings, added to the high concentrations of TRH-like immunoreactivity and receptors present in these nuclei, suggest a possible role of medullary TRH in the vagal regulation of gastric acid secretion.
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PMID:Medullary sites of action of the TRH analogue, RX 77368, for stimulation of gastric acid secretion in the rat. 314 Dec 37

Because arginine vasotocin (AVT) activates male sexual behaviors in the rough-skinned newt (Taricha granulosa), quantitative autoradiography with radiolabelled arginine vasopressin (3H-AVP) was used to characterize putative AVT receptors in the telencephalon of this amphibian. Analyses were restricted to specific binding sites in the medial pallium, although dense binding also was observed in the dorsal pallium and amygdala pars lateralis. Binding of 3H-AVP to these sites was saturable, specific, reversible, of high affinity (Kd = 1 nM) and low capacity (57 fmol/mg protein). The rank order of potency of related peptides in inhibiting 3H-AVP binding was as follows: AVT greater than d(CH2)5[Tyr(Me)2]AVP (a mammalian pressor antagonist) greater than AVP, oxytocin, and [dPen1Tyr(Me)2]AVP (also a pressor antagonist) greater than mesotocin much greater than desGly(NH2)AVP, AVP fragment 4-9 and pressinoic acid. Thus, these binding sites appear to represent authentic central nervous system receptors for AVT. Furthermore, ligand specificity for the binding sites in this amphibian differ from that reported for AVP binding sites in rat brains. The AVT receptors in the medial pallium, dorsal pallium, and amygdala pars lateralis may represent site(s) of action where AVT elicits sexual behaviors in male T. granulosa.
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PMID:Autoradiographic characterization of binding sites labelled with vasopressin in the brain of a urodele amphibian. 317 42

Treatment of a mixture of Cys(R)(O) and Cys(R') with an acid was found to generate cystine in fairly good yields, when suitable R, R', and an acid were selected. An unsymmetrical cystine peptide was prepared by treatment of a mixture of Z(OMe)-Cys(R) (0)-Ala-NH2 (R = Acm or MBzl) and Z(OMe)-Cys(MBzl)-Gly-OBzl with TFA or 1 M TFMSA/TFA3. Oxytocin was obtained in an excellent yield by TFA treatment of the protected peptide containing Cys(Acm)(0) and Cys(MBzl). Thus, formation of the disulfide bond was found feasible at the position of Cys(R) (0).
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PMID:Studies on peptides CLVIII. Model experiments for the synthesis of open-chain unsymmetrical cystine-peptides. 325 66

Oxytocin (OXT) reduced locomotion, rearing, grooming and bolus production in a circular open field at 15 min, but not at 60 min, after a subcutaneous (s.c.) injection. The OXT fragments OXT-(1-8), OXT-(4-9), OXT-(4-8), OXT-(5-9) and OXT-(5-8) had no effect at 15 min or 60 min after s.c. injection. OXT and its fragments attenuated passive avoidance behavior following postlearning (consolidation test) or preretention (retrieval test) injection. Some of the fragments were more potent than the parent molecule. The extinction of pole-jumping avoidance behavior was inhibited by OXT-(1-9) in doses of 1 and 3 micrograms s.c. Doses lower than 1 microgram had no effect or even tended to facilitate extinction. This bimodal effect was more pronounced when OXT fragments OXT-(4-9) and OXT-(5-9) were used. S.c. injection of these peptides in low doses (0.01-0.001 microgram) caused facilitation, and in doses higher than 0.1 microgram inhibition, of pole-jumping avoidance behavior. Removal of the Gly9-NH2 moiety eliminated the bimodal effect; such peptides (OXT-(1-8), OXT-(4-8), OXT-(5-8) caused facilitation of extinction only. Since the C-terminal peptides Pro-Leu-Gly-NH2 and Leu-Gly-NH2 both seem to inhibit extinction of pole-jumping avoidance behavior, it is possible that there are two sequences in the OXT molecule, which act in opposite ways.
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PMID:Bimodal effect of oxytocin on avoidance behavior may be caused by the presence of two peptide sequences with opposite action in the same molecule. 336 72

The presence of vasopressin receptors of the V1 (vascular) type and of oxytocin receptors in the rat kidney was investigated using an autoradiographical approach. Rat kidney sections were incubated with tritiated vasopressin ([3H]vasopressin, 1.5 nM) or oxytocin ([3H]oxytocin, 3 nM). The ligand selectivity of the [3H]vasopressin binding sites detected was deduced from competition experiments using one selective unlabeled ligand for V2 (antidiuretic) vasopressin receptors (1-deamino-[8-D-arginine]-vasopressin, dDAVP) and one selective unlabeled ligand for V1 receptors (des-glycineamide-[1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid]-arginine vasopressin, des(Gly(NH2)9d(CH2)5-AVP). Specific and dense [3H]vasopressin labeling was observable in the medullopapillary and cortical portions of the kidney. Specific [3H]vasopressin binding in the cortex was insensitive to the V1-selective ligand, des(Gly(NH2)9d(CH2)5-AVP, but was inhibited by dDAVP. Glomerular structures identified as such by microscopical observation of the kidney sections were specifically labeled with [3H]oxytocin and [125I]-SAR1-angiotensin II but not with [3H]vasopressin. It is concluded that V1 receptors which have been evidenced on mesangial cells in culture are not expressed in a detectable quantity on mesangial cells in situ. The specific [3H]oxytocin binding to glomeruli might reflect the presence on glomerular structures of oxytocin receptors involved in the effects of the hormone on renal hemodynamics, and possibly in some of the effects ascribed to vasopressin.
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PMID:Autoradiographic localization of vasopressin and oxytocin binding sites in rat kidney. 339 84


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