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

Using immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptide Y, somatostatin, and cholecystokinin immunoreactivity have been identified in all seven supratentorial anaplastic astrocytomas studied. These neurones have been shown not only on the edge but also in the depth of the neoplastic tissue. These neuropeptides were not present in 18 other intracranial tumours (3 astrocytomas, 1 subependymoma, 8 glioblastoma multiformes, 1 meningioma, and 5 metastases). In all 25 intracranial tumours studied, no immunoreactivity was found for vasoactive intestinal polypeptide, substance P, methionine-enkephalin, leucine-enkephalin, synenkephalin, neurophysin I-II, and corticotropin releasing factor.
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PMID:Neuropeptide Y, somatostatin, and cholecystokinin neurone preservation in anaplastic astrocytomas. 290 6

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

The effects of oxytocin (OXT) and of dipeptides derived from the C-terminal portion of oxytocin (Z-prolyl-leucine and Z-prolyl-D-leucine) on the development of acute and chronic tolerance to, and dependence on morphine were tested in the mouse. Oxytocin and the dipeptides attenuated the development of acute and chronic tolerance to the antinociceptive effect of morphine and delayed the onset of the naloxone-precipitated withdrawal syndrome. Both oxytocin and Z-prolyl-D-leucine affected drug-induced behavioural responses related to dopamine (DA) in the brain. Thus, oxytocin potentiated the hypermotility induced by a large dose of apomorphine and decreased the supersensitivity of the DA receptors. Small doses of Z-prolyl-D-leucine inhibited the hypomotility elicited by a small dose of apomorphine and potentiated the hyperactivity induced by amphetamine. The data indicate that both oxytocin and Z-prolyl-D-leucine affect tolerance to and dependence on morphine. While oxytocin interacts mainly with postsynaptic DA-ergic neuronal elements, the dipeptide primarily affects DA-ergic neurotransmission at the presynaptic level.
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PMID:Oxytocin and a C-terminal derivative (Z-prolyl-D-leucine) attenuate tolerance to and dependence on morphine and interact with dopaminergic neurotransmission in the mouse brain. 299

Neuropeptides and biogenic amines known to be present in neurons or afferent terminals in the paraventricular nucleus (PVH), supraoptic nucleus (SON) and/or lateral hypothalamus (LH) were added to small areas of these structures obtained by micropuncture and cyclic adenosine monophosphate (cAMP) levels were measured. cAMP accumulation occurred in PVH, SON and LH in response to neuropeptides of the secretin family, such as vasoactive intestinal peptide (VIP) and in response to catecholamines. Bradykinin, alpha-melanocyte-stimulating (alpha-MSH), luteinizing hormone-releasing hormone (LH-RH), oxytocin and carbamylcholine stimulated cAMP accumulation selectively in one or two of the above structures. Glucagon, cholecystokinin (CCK), somatostatin (SRIF), corticotropin-releasing factor (CRF), thyrotropin-releasing hormone (TRH), adrenocorticotropin (ACTH), melanocyte-stimulating hormone (MSH), methionine enkephalin (Met-Enk), beta-endorphin, neurotensin, bombesin and angiotensin II did not effect cAMP levels while leucine enkephalin (Leu-Enk), arginine vasopressin and gamma-aminobutyric acid (GABA) elicited regionally selective decreases in basal levels of cAMP. When interactions between some of these compounds were measured, VIP and norepinephrine exerted a more than additive effect on cAMP elevation in the PVH, while the effect on cAMP of the SON and LH was additive.
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PMID:Interaction of neuropeptides and biogenic amines on cyclic adenosine monophosphate accumulation in hypothalamic nuclei. 300 57

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

The hormonally and behaviorally active nonapeptide oxytocin (OXT), its behaviorally active N-terminal octapeptide desglycinamide9-OXT and Z-prolyl-D-leucine, a synthetic analog of the C-terminal prolyl7-leucine8 sequence, inhibited the development both of a moderate and of a strong tolerance to morphine. N-alpha-Acetyl-(2-0-methyltyrosine)-OXT and (penicillamine1-2-0-methyltyrosine)- lysine8-vasopressin, both OXT receptor antagonists, facilitated the development of a moderate morphine tolerance. The i.c.v. injection of either antagonist prevented the effects of i.c.v. and s.c. OXT treatment on the development of tolerance. The effect of desglycinamide9-OXT, but not that of Z-prolyl-D-leucine was also prevented by N-alpha-acetyl-(2-0-methyltyrosine)-OXT. It is concluded that OXT and desglycinamide9-OXT, but not Z-prolyl-D-leucine, attenuate morphine tolerance by affecting putative oxytocinergic binding sites in the mouse brain. The fact that i.c.v. injection of the receptor antagonist also blocked the effect of s.c. OXT treatment argues in favor of the possibility that a minor proportion of s.c. OXT (or behaviorally active fragments thereof) may reach central nervous system target sites.
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PMID:Effects of oxytocin-related peptides on acute morphine tolerance: opposite actions by oxytocin and its receptor antagonists. 303 20

Whole brain synaptosomes contain both an isorenin activity and angiotensin-related carboxypeptidase activity. Further hydrolysis of des-Leu angiotensin I (AI-dL) occurs more slowly; hydrolysis of angiotensin II (AII) is negligible. Vasopressin and oxytocin but not vasotocin can inhibit angiotensin-related carboxypeptidase activity. Since AII has been shown to induce vasopressin secretion, this correlation suggests a feedback inhibition by vasopressin of this enzymatic cascade. Commercially available radioimmunoassays for AI and AII show a 3.4 and 6.0% crossreactivity, respectively. When the absolute concentration of AI-dL exceeded 500 ng/ml, both antibodies to AI and AII showed maximal displacement of radiolabel. This suggests that these antibodies may not distinguish between AI-dL from other peptides during immunocytochemistry.
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PMID:Subcellular localization in rat brain of angiotensin-related carboxypeptidase activity distinct from converting enzyme. 319 54

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 effects of colchicine on neurosecretory neurons of the rat hypothalamus were studied by immunocytochemistry, high-resolution radioautography, and conventional electron microscopy. In control rats, intraneuronal immunocytochemical labeling of vasopressin, oxytocin and somatostatin occurred essentially in the Golgi apparatus, the neurosecretory granules and to a lesser extent, the endoplasmic reticulum. These immunostaining patterns were dramatically modified 24 h after the administration of colchicine: immunoreactive peptides were located in granular or tubular structures accumulated at the periphery of the perikarya, but the Golgi stacks were not immunostained. Two h after the administration of tritiated leucine, quantitative analysis of radioautographic labeling of supraoptic perikarya revealed large amounts of radioactive protein in the Golgi saccules of neurosecretory neurons in control rats, but in the neurons of colchicine-treated rats, radioautographic labeling was mainly located in granular structures accumulated at the periphery of the perikarya, with no significant labeling on the Golgi stacks. Lastly, 3 noteworthy effects of colchicine on the ultrastructural morphological features of these neurosecretory neurons consisted in: (1) a dramatic disorganization of the Golgi complexes, (2) an accumulation of electron-dense proteic material within the lumen of cisternae of both the rough and smooth endoplasmic reticulum and, (3) a marked depolymerization of perikaryal microtubules, specifically those associated with the Golgi stacks. Taken together, these data do not fit the prevailing concept that the colchicine-induced accumulation of secretory material within the perikarya of neurosecretory neurons essentially results from the blockade of axoplasmic transport mechanisms. Instead, they support the idea that the effects of colchicine are related to the inhibition of the intraneuronal transport of newly synthesized secretory material from the endoplasmic reticulum to the Golgi apparatus, suggesting that the microtubules associated with the Golgi stacks are possible sites of colchicine action.
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PMID:Effects of colchicine on the intraneuronal transport of secretory material prior to the axon: a morphofunctional study in hypothalamic neurosecretory neurons of the rat. 340 58

We examined opioid binding in fractions with disconnected nerve endings (secretosomes) which were prepared from porcine neurohypophyses by centrifugation in a discontinuous Percoll gradient. Specific (= displaceable) binding was observed with 3H-etorphine and with 3H-diprenorphine, two ligands with low selectivity for distinct opiate receptor subclasses. No displaceable binding was found with the prototypic mu- and delta-ligands 3H-dihydromorphine and 3H-(D-Ala, D-Leu) enkephalin. Displacement of 3H-diprenorphine binding was almost absent with the selective mu- and delta-ligands morphiceptin and ICI-174864. Partial displacement occurred with the selective kappa-ligand U-50488 and with dynorphin. Binding of 3H-etorphine was stereo-specific. 3H-diprenorphine binding was saturable with a KD between 2 and 4 nM. Maximum of opiate binding activity was detected in the fractions with accumulated secretosomes. By autoradiography specific 3H-diprenorphine binding is shown to be mainly associated with secretosomes. In imunocytochemical preparations an oxytocin antibody was immunoreactive in 85% of the secretosomes in the fraction with highest opiate binding. These fractions in radioimmunoassays exhibited the largest contents in oxytocin and low vasopressin levels. The data therefore suggest that in the porcine neurohypophysis opioid binding sites of the kappa-type occur in secretory endings presumably of the oxytocin type.
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PMID:Opiate binding differentially associated with oxytocin and vasopressin nerve endings from porcine neurohypophyses. 340 60


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