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)

We recently reported that acute pharmacologic depression of dopaminergic tone at different times of day unmasks a sex-specific endogenous stimulatory rhythm regulating PRL secretion. The PRL secretory responses of ovariectomized rats to the dopamine antagonist domperidone (DOM) were higher at 0300 and 1700 h than at 1200 h. These are the times during which surges of PRL appear in mated rats. This experimental paradigm was used to investigate the roles of the putative PRL-releasing factors (PRFs) oxytocin (OT), vasoactive intestinal peptide (VIP), and serotonin (5-HT) in this rhythm. The role of OT was studied by infusion of the OT antagonist 1-deamino-2-D-Trp-4-Val-8-Orn-Oxytocin (OT-A, 0.5 microgram/kg min) for 6 h. Two hours after beginning the OT-A infusion DOM was administered, as a single injection of 200 micrograms/kg iv at either 0300, 1200, or 1700 h. Serial blood samples were collected immediately before and 5, 10, 20, 30, 60, 120, 180, and 240 min after DOM administration. Infusion of OT-A attenuated the heightened PRL secretory responses to DOM given at both 0300 and 1700 h but did not affect the response at 1200 h. The role of VIP was studied by infusing the VIP antagonist [D, 4-Cl-Phe6,Leu17] VIP (VIP-A, 0.1 microgram/kg.min) as described above. VIP-A infusion had no effect on the PRL secretory responses to DOM given at 1200 or 1700 h but attenuated the heightened response at 0300 h. In order to study the role of 5-HT in the rhythm, rats were pretreated with p-chlorophenylalanine (250 mg/kg sc) 48 and again 24 h before the experiment. Pretreatment with p-chlorophenylalanine had no effect on the PRL secretory responses to DOM given at 0300 or 1200 h, but it attenuated the augmented PRL secretory response at 1700 h. These data suggest that both VIP and OT act as endogenous PRFs at 0300 h and 5-HT and OT act as PRFs at 1700 h. We propose that VIP and 5-HT are continuously active oscillatory neurotransmitters regulating OT release into pituitary portal blood and that these daily events only eventuate in PRL release when the mating stimulus has release the lactotroph from the inhibitory effects of dopamine.
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PMID:Hypothalamic factors involved in the endogenous stimulatory rhythm regulating prolactin secretion. 252 68

The ability of centrally administered vasoactive intestinal peptide (VIP) to stimulate PRL secretion when injected intracerebroventricularly could be due to leakage to the pituitary, where it is known to exert direct PRL-releasing activity, or to a hypothalamic action on its own release or that of another possible PRL-releasing factor. When 3 micrograms VIP were injected into the third ventricle of conscious ovariectomized rats, a significant (P less than 0.005) and transient elevation of plasma oxytocin (OT) levels was observed. When OVX rats were injected iv with 1 ml anti-OT serum 30 min before the central administration of 3 micrograms VIP, the PRL surge seen after VIP injection in normal rabbit serum-treated controls was completely absent. The PRL surge seen after central VIP administration was not significantly altered by iv saline infusion (1 ml over 30 min) or by infusion of a VIP antagonist [D-4-Cl-Phe6,Leu17]VIP at a dose of 0.5 microgram/kg.min in 1 ml saline for 30 min before the VIP injection. This was not due to the inability of the VIP antagonist to block the PRL-releasing factor activity of VIP, since it significantly antagonized that action both in vitro and in vivo in the suckling stimulation paradigm. However, the PRL surge was completely absent in ovariectomized rats pretreated by iv infusion of an OT antagonist, [deamino Cys1,D-Trp2,Val4,Orn8]OT, at a similar dose. This recruitment of OT by VIP indicates that it may act at more than one locus within the hypothalamo-pituitary axis to insure the coordinated control of PRL secretion.
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PMID:Oxytocin mediates the hypothalamic action of vasoactive intestinal peptide to stimulate prolactin secretion. 291 3

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

Vasoactive intestinal polypeptide (VIP)ergic nerves innervate both the neurohypophysis and the hypothalamus. To test the hypothesis that VIP is a releasing factor for neurohypophyseal hormones, rats were given intracerebroventricular (icv) infusions of VIP in doses varying from 0.3 pmol/kg.min to 3 nmol/kg.min for 5 min (0.001-10 micrograms/rat). Serial blood samples were drawn from the vena cava for measurement of oxytocin (OT), vasopressin (AVP), and VIP by RIA. After the VIP infusions mean plasma OT and AVP levels rose in a dose-dependent manner; the rise was significant for both hormones at the dose of 300 pmol/kg.min. Peak levels after infusion of 3 nmol/kg.min were greater for OT than AVP [96.1 +/- 14.7 vs. 33.9 +/- 9 microU/ml (mean +/- SE); n = 6]. In addition, the concentration of plasma OT increased more promptly than that of AVP. Plasma OT was significantly raised over control values at 5 min, whereas plasma AVP was not increased until 15 min after the VIP infusion began. The concentration of VIP in peripheral plasma rose somewhat after icv infusions (maximum, 300 pmol/liter 30 min after 10 micrograms/rat), but the rise was only 5% of that observed after systemic infusions of equimolar doses of VIP (maximum, 6000 pmol/liter 5 min after 10 micrograms/rat). Peak plasma OT levels after administration of 3 nmol/kg.min VIP were significantly higher after icv than after systemic infusion of the same dose of VIP reported previously. Intravenous injection of 0.5 ml VIP antiserum with a binding capacity of VIP of 2.3 micrograms/ml before the icv administration of VIP (1 microgram/rat) did not prevent the VIP-induced rise in plasma OT and AVP. These observations suggest a central site of action for VIP in OT and AVP release, probably in the hypothalamus. The results are in harmony with the hypothesis that endogenous VIP is a physiological regulator of OT and AVP release in rats.
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PMID:Release of oxytocin and vasopressin by intracerebroventricular vasoactive intestinal polypeptide. 316 20

The effect of 15 defined neuropeptides on the mitogenic activation of lymphocytes from human thymus, guinea pig lymph nodes and rat spleen was investigated. Lymphocytes were incubated in the absence or presence of polyclonal T and B cell activators together with increasing doses of the neuropeptides, and harvested at 48 h of culture after pulse-labeling with 3H-thymidine to assess the DNA synthesis. A dose-related stimulatory effect on the spontaneous 3H-thymidine incorporation of human thymocytes was obtained with methionine-enkephalin (met-enk), motilin and neurotensin. Vasoactive intestinal polypeptide (VIP) and peptide HI (PHI) were inhibitory. A similar responsiveness was observed in cultures of phytohemagglutinin P (PHA)-activated human thymocytes. The low level of basal DNA synthesis of guinea pig lymph node cells was stimulated by VIP and inhibited by neuropeptide Y (NPY) and PHI. PHA-activated lymph node T lymphocytes were stimulated by neurotensin, bombesin and motilin, whereas NPY inhibited the thymidine uptake. The low rate of spontaneous DNA synthesis of rat spleen cells was increased in the presence of VIP. Met-enk stimulated both basal and dextran sulfate-activated splenic B cell proliferation, whereas PHI was inhibitory in both cases. The following peptides were found to be inactive in all the above assays: substance P, cholecystokinin-octapeptide, somatostatin, galanin, oxytocin, pentagastrin and gastrin-releasing peptide 1-27 and 14-27. Although the responses were generally of low magnitude and observed at high peptide concentrations, present study contributes to the understanding of possible mechanisms involved in interactions between the nervous and the immune system.
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PMID:Neuropeptide regulation of human thymocyte, guinea pig T lymphocyte and rat B lymphocyte mitogenesis. 349 94

Vasoactive intestinal polypeptide (VIP) was infused into the aorta of pentobarbitone-anesthetized rats (n = 12) in stepwise increasing doses of 0.001 to 10 micrograms/rat at rates varying from 0.3 pmol/min/kg to 3000 pmol/min/kg over 3 min. Blood was withdrawn from the vena cava inferior for the measurement of oxytocin (OT) and vasopressin (AVP) by RIA. The loss of blood was compensated for by infusion of isotonic saline (0.9% NaCl with 0.5% human serum albumin). Control rats received this solution only (n = 11). VIP infusions resulted in a dose-dependent increase in plasma OT which was significantly greater than the slight rise observed in the controls. The difference from controls was significant at infusion rates of 3 pmol/min/kg and more. Plasma AVP, on the other hand, did not rise in response to VIP infusions until the infusion rate was increased to 300 and 3000 pmol/min/kg. At these infusion rates, the increments in AVP were much smaller than those of OT, the levels during the highest infusion rates rising to 8.6 +/- 2.8 and 27.2 +/- 4.8 microU/ml, respectively (log normal means). The preferential release of OT in response to exogenous VIP in rats differs from the response in cats where intracarotid administration of VIP resulted in the release of proportionately more AVP than OT. Immunoreactive VIP is found in the hypothalamo-neurohypophyseal system of rats in close proximity of some of the magnocellular neurons as well as within the nerve terminals. This, together with our data, suggests that endogenous VIP may participate in the release mechanism for OT in rats.
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PMID:Preferential release of oxytocin in response to vasoactive intestinal polypeptide in rats. 379 18

The brain contains a large variety and number of peptides some of which were known earlier as hypothalamic hormones (vasopressin, oxytocin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, somatostatin) or as pituitary hormones (the family of opiomelanocortins), while others, not primarily known as hypothalamic or pituitary hormones, may also have endocrine effects (substance P, angiotensin II, neurotensin, bombesin, vasoactive intestinal peptide (VIP), gastrin-cholecystokinin, glucagon, carnosine, bradykinin). These peptides, which form a new class of putative neurotransmitters, are present early in brain development and show important sex differences in both their pattern of innervation and their effects. Their peripheral effects may include intrauterine growth of the placenta and fetus, the timing of birth, acceleration of the course of labour and responses to haemorrhage (redistribution of cardiac output and stimulation of blood cell formation). Endogenous peptides are probably involved in brain development, which may explain their general, permanent and sex-dependent effects when given in the period of rapid brain development. Although peptides might in the future be useful for stimulating recovery from retarded brain development, at present one should be aware of the potential dangers of their use in, for example, obstetrics.
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PMID:Development of peptidergic systems in the rat brain. 627 64

The concentration of vasoactive intestinal peptide (VIP) was measured by RIA in pituitary extracts of female cats; it was significantly higher in the posterior than in the anterior lobe, 47.3 +/- 3.9 pmol/g wet wt vs. 7.7 +/- 2.0 pmol/g wet wt (mean +/- SE, n = 5 in both instances). To investigate the effect of VIP on the release of posterior pituitary hormones, the concentration of arginine vasopressin and oxytocin was measured by RIA in jugular vein plasma during intracarotid infusion of VIP. The levels of both hormones rose during the 5-min infusion of VIP. Oxytocin levels increased from a mean of 7.9 microU/ml to a maximum of 34.9 microU/ml at 1 min and arginine vasopressin levels from from 27.4 microU/ml to a maximum of 157 microU/ml at 1 min. The levels of both hormones returned to baseline values in about 20 min. Since VIP has been localized to the nerve terminals of the neurohypophysis, these data suggest that endogenous VIP may play a role as a neurotransmitter in the magnocellular hypothalmo-neurosecretory system.
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PMID:Vasoactive intestinal peptide (VIP) stimulates oxytocin and vasopressin release from the neurohypophyis. 647 4

An indirect immunofluorescence technique was used to study the peptidergic innervation of the thyroid gland in homozygous Brattleboro rats (DI) and normal Long-Evans rats (LE). The primary goal of this study was to determine whether the previously demonstrated decrease in thyroid responsiveness to TSH in DI might be due to an abnormality in the innervation of the thyroid. Thyroids from both types of rats were found to contain nerve fibers containing immunoreactivity for vasoactive intestinal peptide (VIP), substance P (SP), neuropeptide Y (NPY), and peptide HI (PHI). All four types of fibers were found in close association with both follicle cells and blood vessels. Well developed networks of fibers surrounding blood vessels were particularly apparent in the case of NPY. The density of fibers associated with follicle cells in DI was at least as great as that in LE in regard to SP, NPY, and PHI. Fibers containing VIP were found in greater abundance in DI than in LE. Additional studies revealed no evidence of thyroid fibers containing either somatostatin or neurophysin, which was used as a marker for vasopressin. We conclude that the reduced responsiveness of the thyroid in DI is not due to an inadequate supply of any of the neuropeptides included in this study. Since VIP is known to enhance thyroid secretion, we suggest that the apparent proliferation of VIP-containing fibers in DI may be a reflection of a neural mechanism attempting to compensate for a thyroid gland deficiency analogous to the humoral mechanism by which TSH secretion increases in response to thyroid deficiency.
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PMID:Immunocytochemical studies of the peptidergic innervation of the thyroid gland in the Brattleboro rat. 654 94

1. The action of vasoactive intestinal peptide (VIP) on the electrical and mechanical activity of strips of longitudinal myometrial smooth muscle from rabbits and guinea-pigs treated with oestradiol was studied in the sucrose-gap apparatus. 2. In myometrial strips which spontaneously exhibited regular contractions, or which were induced to contract rhythmically to the application of oxytocin, VIP reduced both the frequency and the force of contraction. 3. Contractions were associated with bursts of action potential discharge. In guinea-pig, the membrane potential reached its most negative value shortly following a burst and a slow decay of negativity followed ("generator potential'). VIP inhibited the decay of this negativity and increased the duration of the period between bursts. In rabbit myometrical strips, electrical discharges occurred less regularly but VIP also had an inhibitory action. The inhibitory action of VIP was not affected by the beta-adrenoreceptor blocker propranolol, by tetrodotoxin, or by apamin. 4. Using the double sucrose-gap apparatus, bursts of action potentials and contractions were elicited with depolarizing electrical pulses in the absence of oxytocin. Changes in membrane resistance were also estimated by eliciting hyperpolarizing electrotronic potentials. VIP hyperpolarized the membrane and inhibited contractions as depolarizing pulses now failed to reach threshold for action potential discharge or fewer action potentials were discharged. A small (about 10%) reduction in membrane resistance was freqeuently observed during the hyperpolarization. 5. If a single action potential was elicited in the presence of VIP, the tension generated by the muscle was less than in its absence. 6. In a calcium-free high-potassium (126 mM) solution, readmitting calcium produced contraction; VIP inhibited this contraction. Activation of beta-receptors by means of isoprenaline had a similar effect but unlike isoprenaline the action of VIP was not blocked by propranolol. 7. It is suggested that the primary action of VIP is on the calcium economy of the myometrial smooth muscle cell, possibly to accelerate sequestration and/or extrusion of calcium from the cell. In some way this is associated with inhibition of the generator potential, hyperpolarization, and with a small increase in permeability of the membrane to potassium.
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PMID:Mechanism of action of vasoactive intestinal polypeptide on myometrial smooth muscle of rabbit and guinea-pig. 732 Aug 97


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