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)

A synthetic procedure was developed for the direct immobilization on preactivated affinity supports of peptidic ligands requiring free alpha-amino groups to recognize their targets properly. The peptidic ligand is assembled by solid-phase peptide synthesis on an octa-branched heptalysine core through a polyglycine spacer, similar to the method developed for the production of multiple antigenic peptides. After deblocking from the resin, peptide is dialysed, lyophylized and used directly for coupling to preactivated supports. Following immobilization, only a limited number of peptide chains are covalently linked to the solid phase, leaving the remainder facing the mobile phase and sufficiently spaced to interact properly. This procedure was applied successfully to the design, synthesis and oriented immobilization of a multimeric tripeptide ligand (Met-Tyr-Phe) for affinity purification of bovine neurophysin.
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PMID:Oriented immobilization of peptide ligands on solid supports. 161 62

The neurointermediate lobe of the pituitary (NIL) contains the opioid peptides methionine enkephalin (MENK) and dynorphin 1-8 (DYN) in addition to oxytocin (OT) and vasopressin (AVP). If the opioids have a functional role, such as feedback control on OT or AVP release, the content or release of the opioids might be expected to change under conditions in which OT or AVP change. This expectation was examined by studying the synthesis, storage and release of the 4 peptides under conditions in which OT and AVP dynamics are known to be altered. Diestrus, diethylstilbesterol(DES)-treated, and day 22 pregnant rats were decapitated, the hypothalamo-neurohypophysial system (HNS) excised and either superfused in oxygenated Krebs buffer at 37 degrees C or stored at -80 degrees C for measurement of paraventricular and supraoptic nuclei mRNA content by in situ hybridization analysis. Peptide content of superfusates and NIL homogenates were determined by specific RIAs. Compared with diestrus animals, DES treatment increased NIL OT but decreased MENK. In term pregnant rats, NIL OT, AVP, and DYN were increased over diestrus values, while MENK was again decreased. Release of the peptides from the isolated HNS paralleled changes in NIL content. The hypothalamic mRNA for OT was increased in DES-treated and pregnant rats while MENK mRNA was decreased. AVP and DYN mRNA was increased in pregnant animals. Although the NIL was found to contain much more immunoreactive OT and AVP than MENK or DYN, under basal conditions the release of MENK was equal to or greater than the release of OT, while the release of DYN approached that of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diethylstilbesterol- and pregnancy-induced changes in rat neurointermediate lobe oxytocin, arginine vasopressin, methionine enkephalin and dynorphin. 168 32

Cross-reaction of a rat monoclonal antibody (BTP-1) against seventeen substance P analogues was studied. The antibody was of IgG type and related to the carboxyl terminal of substance P, especially methionyl in the terminal, but did not depend on the strength of antagonistic effects of these analogues. It did not show cross-reaction with the following nine peptides: glucagon, endorphin, angiotensin I, II, leucine-enkephalin, methionine-enkephalin, bradykinin, oxytocin and dernorthin, indicating its high specificity to substance P. By means of immuno-enzyme histochemical method, it was shown that stained nerve fibers were located in the gelaliternous substance of Rolando, interpeduncular nucleus, substantia nigra and nerve cell bodies in the vestibular nucleus, lateral tegmental nucleus of mesencephalon and ventral region of third ventricle.
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PMID:[Study of characteristics of monoclonal antibody against substance P]. 169 64

The intrinsic innervation of the human uterine artery was investigated histochemically, and the motor responses to some of the demonstrated peptides and other humoral factors were studied on isolated vascular preparations. There were nerves with specific immunoreactivities for tyrosine hydroxylase, dopamine beta-hydroxylase, neuropeptide-Y (NPY), vasoactive intestinal peptide (VIP) and peptide histidine methionine, and enzymatic reactivity for acetylcholine esterase. The most effective stimulator of smooth muscle contractility was arginine vasopressin followed in order by oxytocin, noradrenaline together with NPY, noradrenaline alone and dopamine. No effect was seen with acetylcholine and tyrosine, and VIP caused inconsistent relaxation of contractile activity induced by PGF2 alpha. These results suggest that the uterine blood flow is regulated by complex interactions of factors, some occurring in nerve terminals and some being circulating humoral factors.
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PMID:Innervation of the human uterine artery and contractile responses to neuropeptides. 201 Jan 12

The response to small peptides such as Arg-vasopressin, oxytocin and tachykinins was investigated in cultured porcine aortic endothelial cells. The production of endothelium-derived nitric oxide was assessed indirectly by the accumulation of cyclic GMP, a response that is due to the increased activity of soluble guanylate cyclase of the endothelial cells after release of the mediator. Arg-vasopressin, oxytocin, substance P and physalae-min (an analog of substance P, pGlu-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-Gly-Leu-Met-NH2) markedly and transiently stimulated the production of cyclic GMP without affecting that of cyclic AMP. Treatment of endothelial cells with either hemoglobin or methylene blue reduced significantly both the basal and stimulated level of cyclic GMP. The production of cyclic GMP evoked by Arg-vasopressin and substance P was inhibited selectively by NG-monomethyl-L-arginine but not by its D-enantiomer. The neurohypophyseal hormones and related peptides stimulated the accumulation of cyclic GMP in a concentration-dependent manner, with the following relative order of potency: oxytocin greater than Lys-vasopressin greater than Arg-vasopressin much greater than [deamino-Cys1, D-Arg8]-vasopressin. The production of cyclic GMP evoked by oxytocin was inhibited selectively by [d(CH2)5, Tyr(OMe)2, Orn8]-vasotocin, an oxytocin antagonist. The production of cyclic GMP evoked by Arg-vasopressin and Lys-vasopressin was inhibited by [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin, a selective V1-receptor antagonist. The moderate production of cyclic GMP evoked by [deamino-Cys1, D-Arg8]-vasopressin was inhibited significantly by the V1-receptor antagonist. The peptide antagonists affected only minimally or not at all the production of cyclic GMP evoked by a donor of nitric oxide, SIN-1 (3-Morpholino-Sydnonimine). These observations indicate that 1) neurohypophyseal hormones and tachykinins stimulate the accumulation of cyclic GMP in cultured porcine aortic endothelial cells by increasing the production of endothelial-derived nitric oxide, which in turn enhances the activity of soluble guanylate cyclase; 2) the production of cyclic GMP in response to oxytocin is due to activation of oxytocinergic receptors; and 3) the production of cyclic GMP evoked by Arg-vasopressin and Lys-vasopressin is due mostly to activation of V1-vasopressinergic receptors.
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PMID:Neurohypophyseal peptides and tachykinins stimulate the production of cyclic GMP in cultured porcine aortic endothelial cells. 217 9

The distribution of leucine-enkephalin, methionine-enkephalin, neurotensin, somatostatin, substance P, oxytocin, vasopressin, neurophysin II, and serotonin in nerve terminals and fibers of sympathetic autonomic areas of the thoracolumbar (T-L) spinal cord was studied immunohistochemically in cats. Densities of these immunoreactive terminals and fibers were estimated in the intermediolateral nucleus pars principalis (IMLp) and pars funicularis (IMLf), the nucleus intercalatus (IC), and the central autonomic area (CA). Results for leucine- and methionine-enkephalin-like immunoreactivity (ENK) were similar and immunoreactivity for vasopressin was not observed. The greatest numbers of terminals and fibers in the IMLp region contained ENK, neurotensin-(NT), and serotonin-like immunoreactivity (5HT); terminals and fibers containing substance P-(SP) and neurophysin II-like immunoreactivity (NP2) were intermediate in number, and those containing somatostatin-(SS) and oxytocin-like immunoreactivity (OXY) were generally sparse. In the IC and CA, terminals and fibers containing ENK and NT were dense, those containing SP were moderate, and those containing OXY, NP2, and 5HT were sparsely represented. In the IMLp, where the largest proportion of sympathetic preganglionic neurons (SPN) is found, the greatest concentration of terminals and fibers containing ENK was found in segments T1-T8; for NT these segments were T1-T5 and T11-L1, for SP-C8-T2 and T11-L1, for NP2-T4-T7 and L2 to L3, and for 5HT-T1-T5. Terminals and fibers containing SS and OXY were present in segments C8-T10 and segments C8, T2-T8, T13, and L2 to L3, respectively. These results indicate that while ENK, NT, SP, NP2, and 5HT fibers and terminals are widely distributed throughout the T-L cord, they may influence to a greater degree the SPN in segments where they are present in greater numbers. As SS and OXY were not found at all levels of the IMLp, their functions may be more organ specific.
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PMID:Segmental distribution of peptide- and 5HT-like immunoreactivity in nerve terminals and fibers of the thoracolumbar sympathetic nuclei of the cat. 241 41

The distribution of leucine-enkephalin, methionine-enkephalin, neurotensin, somatostatin, substance P, oxytocin, vasopressin, and neurophysin II in cell bodies of sympathetic autonomic nuclei of the thoracolumbar (T-L) spinal cord was studied immunohistochemically in cats after intrathecal administration of colchicine. Neurons containing only enkephalin-, neurotensin-, somatostatin-, and substance P-like immunoreactivity (ENK, NT, SS, SP, respectively) were found in the intermediolateral nucleus pars principalis (IMLp) and pars funicularis (IMLf), the nucleus intercalatus (IC), and the central autonomic area (CA). The size, shape, location, and numbers of the peptide-positive neurons in the IMLp, IMLf, and IC suggested that they were sympathetic preganglionic neurons (SPN). This was confirmed by a combined retrograde tracing/immunohistochemical study showing that most of these neurons at the levels of the T-L cord known to provide preganglionic fibers to the stellate ganglion were SPN. On the other hand, the functional identification of the neurons in the CA is uncertain as neurons were not observed which were both retrogradely labelled and contained ENK, NT, SS, or SP. Immunoreactive neurons in each area were counted in ten sections from each segment from C8 to L4. In the IMLp, the SPN with ENK were greatest in number (up to 25) in segments T4-T7 and L2-L3. The maximum number of SPN containing NT was found in segments T4-T7 (45 neurons). Of the four peptides, neurons containing SS were found in the greatest number (up to 48 in segments T2-T6); neurons containing SP were found in the smallest number (15 or fewer per segment). Few SPN containing each of the four peptides were found in the IC; CA neurons with ENK and NT were also few in number. A comparison of the numbers of immunoreactive neurons in the IML with earlier estimates for the total numbers of SPN in the IML at each level showed that the proportions of IML neurons containing each of the four peptides were fairly consistent throughout the T-L cord, with some exceptions. These results suggest that the innervation of visceral organs is not obviously peptide-specific, although some organs may be innervated by a greater proportion of SPN containing one of these peptides. Finally, the presence of ENK, NT, SS, and SP in SPN suggests that these four peptides act as neurotransmitters in preganglionic pathways to sympathetic ganglia.
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PMID:Segmental distribution of peptide-like immunoreactivity in cell bodies of the thoracolumbar sympathetic nuclei of the cat. 241 42

A bland procedure, conducted in ice, is described for the extraction with HCl of smooth-muscle-contracting substances from plexus-containing ileal longitudinal muscle (l.m.) sheets obtained mainly from rabbits and some guinea-pigs. The spasmogenic activity in rabbit extracts was distinguished from acetylcholine, histamine and 5-hydroxytryptamine by antagonists; and from prostaglandins, by its insolubility in ether at acid pH and by pretreatment of the animals with indomethacin. The fact that it contracts the separated l.m. of the guinea-pig ileum, whether plexus-containing or plexus-free, and in atropine distinguishes it also from methionine-enkephalin, somatostatin, 13-norleucine motilin, bombesin, and cholecystokinin octapeptide (CCK8). This activity was partially purified, first by several partitions with ether at pH 1.4-2.2 and then by treatment at pH 4.5-5 with lead acetate. The virtual absence of ATP was confirmed by the firefly bioluminescence technique. The guinea-pig-ileum-contracting component in the partially purified extracts was destroyed by pepsin, chymotrypsin and DPCC-treated trypsin, indicating its peptide nature and distinguishing it from oxytocin, vasopressin, bradykinin, etc. In parallel assays the partially purified rabbit extracts were considerably more active than Substance P on jird or rat ascending colons than on the guinea-pig l.m., suggesting the presence of a second spasmogenic component in the extracts. In guinea-pig extracts the partially purified activity was 8-16 times greater when plexus-containing than when plexus-free, pointing to Auerbach's plexus as the source of the activity.
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PMID:Extraction and partial purification of spasmogenic substances in Auerbach's plexus. 242 21

We have examined the distribution pattern and the density of various neuropeptide, neurotransmitter and enzyme containing neurons in the rat medial septum and the nucleus of the diagonal band of Broca to assess their possible involvement in the septohippocampal, septocortical and septobulbar pathways. Immunohistochemical methods were combined with the retrograde transport of a protein-gold complex injected in the hippocampus, the cingulate cortex or the olfactory bulb. Cholinergic neurons were the most numerous. Galanin-positive neurons were about two or three times less numerous than cholinergic cells. Both these cell types had a similar location though the choline acetyl transferase-like immunoreactive cells extended more caudally in the horizontal limb of the nucleus of the diagonal band of Broca. Immunoreactive cells for other neuroactive substances were few (calcitonin gene-related peptide, luteinizing hormone releasing hormone. [Met]enkephalin-arg-gly-leu) or occasional (dynorphin B, vasoactive intestinal polypeptide, somatostatin, neurotensin, cholecystokinin, neuropeptide Y and substance P). No immunoreactive cells for bombesin, alpha atrial natriuretic factor, corticotropin releasing factor, 5-hydroxytryptamine, melanocyte stimulating hormone, oxytocin, prolactin, tyrosine hydroxylase or arg-vasopressin were present. Choline acetyltransferase- and galanin-like immunoreactive cells densely participate to septal efferents. Cholinergic neurons constituted the bulk of septal efferent neurons. Galanin-positive cells were 22% of septohippocampal, 8% of septocortical, and 9% of septobulbar neurons. Galanin containing septohippocampal neurons were found in the medial septum and the nucleus of the diagonal band of Broca; galanin-positive septobulbar and septocortical cells were limited to the nucleus of the diagonal band of Broca. Occasional double-labellings were noticed with some peptides other than galanin. Luteinizing hormone-releasing hormone, calcitonin gene-related peptide and enkephalin were the most often observed; some other projecting cells stained for vasoactive intestinal polypeptide or dynorphin B. Luteinizing hormone-releasing hormone, calcitonin gene-related peptide and enkephalin were observed in septohippocampal neurons; luteinizing hormone-releasing hormone and vasoactive intestinal peptide were observed in septocortical neurons and calcitonin gene-related peptide, luteinizing hormone-releasing hormone and dynorphin B were observed in septo-bulbar cells. These results show that, in addition to acetylcholine, galanin is a major cellular neuroactive substance in septal projections to the hippocampus, the cingulate cortex and the olfactory bulb. The presence of septal projecting neurons immunoreactive for other peptides shows that a variety of distinct peptides may also participate, but in a smaller number, to septal efferent pathways.
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PMID:Cholinergic and peptidergic projections from the medial septum and the nucleus of the diagonal band of Broca to dorsal hippocampus, cingulate cortex and olfactory bulb: a combined wheatgerm agglutinin-apohorseradish peroxidase-gold immunohistochemical study. 247 18

The posterior pituitary contains a PRL-releasing factor (PRF), a small (less than 5000 mol wt) peptide which is distinct from known PRL secretagogues. The objectives of this study were to determine if posterior pituitary extracts specifically stimulate PRL release in vivo and to assess the relative contributions of oxytocin (OT), arginine vasopressin (AVP), and beta-endorphin (beta END) to the PRF activity of the extract. Rat posterior pituitaries or cerebellar tissue were extracted with 1.0 N acetic acid, boiled, and ultrafiltered through 5000 mol wt cutoff membranes. The eluates were treated with performic acid (which oxidizes disulfide bonds and methionine residues), lyophilized, and reconstituted in saline. Jugular blood was collected from conscious ovariectomized rats before and after intracarotid injection of test substances and was analyzed for PRL, LH, and GH by RIA. Injection of 0.3, 1.0, and 3.0, posterior pituitary equivalents increased plasma PRL levels by 2-, 8-, and 22-fold, respectively. PRL levels peaked within 5 min after the injection and returned to basal levels by 30 min. Plasma LH levels decreased slightly, and GH was unchanged. Cerebellar extracts did not affect plasma hormone levels. Injection of OT induced a 4-fold rise in plasma PRL levels. Oxidation of OT was well as AVP with performic acid abolished any PRL-releasing activity. Injection of beta END increased plasma PRL levels by 7-fold. Treatment of beta END with performic acid caused a 60% loss in its ability to release PRL. Pretreatment of rats with naloxone abolished the PRL-releasing effect of beta END, but did not alter the PRF activity of posterior pituitary extracts. We conclude that posterior pituitary extracts stimulate PRL release in vivo in the presence of an intact dopaminergic inhibition. This stimulation is rapid, dose dependent, and hormone specific. OT, AVP, and beta END do not contribute significantly to the PRF activity in the posterior pituitary extract.
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PMID:The posterior pituitary contains a potent prolactin-releasing factor: in vivo studies. 252 28


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