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)

The possible role of angiotensin II (AII) in the control of the hypothalamic-pituitary-adrenal (HPA) axis was studied in the rat by examining the regulation and cellular localization of AII receptors in the paraventricular nucleus (PVN) of the hypothalamus and the effect of AII on corticotropin-releasing hormone (CRH) and vasopressin (VP) mRNA levels. In situ hybridization studies using cRNA 35S-labelled probes showed that while type 1 AII receptor (AT1) mRNA levels were high in the periventricular and parvicellular pars of the PVN, only very low levels were present in the magnocellular pars. A similar distribution of AT1 receptor binding in the periventricular, parvicellular and magnocellular divisions of the PVN was observed in autoradiographic studies in hypothalamic sections labelled with 125I[Sar1,Ile8]AII. In addition, AII receptor binding was clearly evident in nerve fibers adjacent to the PVN. Double-labelling hybridization using digoxigenin-labelled CRH, VP and oxytocin probes and 35S-labelled AT1 receptor cRNA probes showed AT1 receptor mRNA in cells stained for CRH mRNA, but not in VP or oxytocin cells. Four hours after a single intracerebroventricular (i.c.v.) injection of 50 ng AII in conscious rats, CRH mRNA levels in the PVN were increased by 43%, similar to the increases observed following acute stress by intraperitoneal (i.p.) injection of 1.5 M NaCl (76%). On the other hand, while i.p. hypertonic saline injection increased VP mRNA levels by 29% in the PVN and by 32% in the supraoptic nucleus, i.c.v. AII injection had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Direct regulation of hypothalamic corticotropin-releasing-hormone neurons by angiotensin II. 778 57

Central serotonin (5-HT) and angiotensin (ANG II) stimulate arginine vasopressin (AVP), oxytocin (OT), and adrenocorticotropin (ACTH) secretion and increase blood pressure. Studies were conducted in conscious rats to determine whether neuroendocrine activation by 5-HT requires a brain angiotensinergic intermediate pathway. In the first study, ANG II formation was inhibited by the angiotensin-converting enzyme inhibitor enalapril before injection of the 5-HT releaser/uptake inhibitor d-fenfluramine. Fenfluramine (2 mg/kg ip) stimulated AVP, OT, corticosterone, and prolactin (PRL) secretion (P<0.01). Enalapril (60 mg/l in drinking water for 4 days and 10 mg/kg ip 2 h before the rats were killed) inhibited only the AVP response (P<0.01) to d-fenfluramine. In the second study, the effect of intracerebroventricular injection of the 5-HT2A/2C antagonist LY-53857 (10 microgram), or the ANG II AT1 antagonist DuP-753 (10 microgram), on intracerebroventricular 5-HT (10 microgram)-stimulated AVP, OT, ACTH, PRL, renin secretion, mean arterial pressure (MAP) and heart rate (HR) was tested. LY-53857 inhibited the AVP, OT, and ACTH responses to 5-HT (P<0.01), whereas DuP-753 inhibited only the AVP response (P<0.01). Intraventricular injection of 5-HT increased MAP and decreased HR. The MAP response was not affected by LY-53857 or DuP-753, and at no time did MAP decline below starting levels. The decreased HR was inhibited by LY-53857 but not by DuP-753. These results demonstrate that 5-HT-induced AVP secretion is mediated selectively via brain angiotensinergic mechanisms by way of the AT1 receptor.
 ...
PMID:Neuroendocrine and cardiovascular effects of serotonin: selective role of brain angiotensin on vasopressin. 863

This study was designed to ascertain whether the extracellular loops of vasopressin/oxytocin receptors bind ligands and, if so, to locate the molecular determinants of this ligand-receptor interaction. Ligand-binding studies were employed using a rat liver V1a vasopressin receptor preparation and both peptide and non-peptide receptor ligands. Synthetic peptides corresponding to defined regions of the extracellular surface of the neurohypophysial hormone receptors recognized radioligands. These receptor mimetics inhibited the binding of radioligands to the V1a receptor with apparent affinities (pKi) ranging from 3.1 to 6.75. The same mimetics had no effects on the binding of angiotensin II to the rat AT1 receptor, indicating specificity for V1a receptor ligands. A mimetic peptide (DITYRFRGPDWL) of the first extracellular loop (ECII) of the V1a vasopressin receptor also inhibited vasopressin-stimulated, but not angiotensin II-stimulated, glycogen phosphorylase in isolated rat hepatocytes. In contrast, scrambled ECII mimetics displayed greatly reduced affinity for vasopressin. In addition, the role of peptide side-chain versus main-chain atoms in the binding of ligands by vasopressin receptors was addressed using retro-inverso peptide mimetics. Our findings indicate a precise orientation of the extracellular receptor surface (particularly the ECII domain) which facilitates the initial 'capture' of both peptide and non-peptide ligands. Moreover, the data indicate that the main-chain atoms of both a major binding-site determinant in the first extracellular loop of the receptor and the neurohypophysial hormones contribute significantly to the ligand-receptor interaction. These findings also suggest that soluble receptor-binding domains have therapeutic potential.
 ...
PMID:Molecular recognition of peptide and non-peptide ligands by the extracellular domains of neurohypophysial hormone receptors. 871 88

The subfornical organ and organum vasculosum laminae terminalis represent neuroglial circumventricular organ structures bordering the anterior third cerebral ventricle. Owing to the absence of the blood-brain barrier, the cellular elements of the subfornical organ and the organum vasculosum laminae terminalis can be reached by circulating messenger molecules transferring afferent information. As demonstrated for the control of extracellular fluid composition, the circulating hormone angiotensin II acts on these sensory circumventricular organs to induce drinking, elevated peripheral resistance and neurohypophyseal hormone release via interaction with membrane-spanning receptor proteins. To characterize the cell-specific distribution of angiotensin II receptors within the circumventricular organs, primary cell cultures derived from the subfornical organ or organum vasculosum laminae terminalis of five- to six-day-old rat pups were used to measure alterations in intracellular calcium at the single cell level. Neurons and astrocytes were identified by immunocytochemical staining for specific marker proteins. Bath application of angiotensin II (10(-10)-10(-6) M) dose-dependently induced calcium transients in neurons (19.6%) and astrocytes (15.7%), and angiotensin II threshold concentrations to elicit intracellular calcium signalling proved to be one order of magnitude higher in astrocytes as compared to neurons (10(-9) M). At angiotensin II concentrations higher than 10(-7) M, pronounced desensitization of the angiotensin II receptor occurred. Employing the angiotensin II receptor antagonists losartan (DUP-753; AT1-receptor) and PD-123319 (AT2-receptor), exclusive expression of the AT1 receptor subtype coupled to intracellular calcium concentration signalling could be demonstrated for neurons and astrocytes. In all cells examined, the angiotensin II-evoked increase in intracellular calcium concentrations could be fully suppressed in the absence of extracellular calcium. Co-activation by angiotensin II and other agents (vasopressin, its fragment 8-arginine-vasopressin(4-9), oxytocin, endothelin) was indicated for subfornical organ neurons and organum vasculosum laminae terminalis astrocytes.
 ...
PMID:Angiotensin II-induced calcium signalling in neurons and astrocytes of rat circumventricular organs. 962 48

Using the immunohistochemical localization of the protein product of the immediate early gene, c-fos, to localize activated neurons in the paraventricular nucleus of the hypothalamus (PVN), we studied the chemical phenotypes of neurons activated by circulating angiotensin II (AII). We determined the proportions of activated PVN neurons that expressed AII type I receptor-like immunoreactivity (AT1-L) or the neurohormones vasopressin (VP) and oxytocin (OXY). In addition, we identified activated PVN neurons that putatively produce nitric oxide (NO) on the basis of histochemical staining for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). Conscious rats received intravenous AII infusions at a rate sufficient to elevate mean arterial pressure by 40-60 mmHg for 90 min; control rats received infusions of vehicle. Brains were prepared for double immunohistochemistry [Fos-like immunoreactivity (FLI)/AT1-L, FLI/VP or FLI/OXY] or FLI/ NADPH-d histochemistry. Systemic AII infusions led to activation of 149+/-14 PVN neurons per section. In contrast, control animals showed activation of 21+/-6 PVN neurons per section. AII infusions elicited the activation of the following numbers of chemically identified PVN neurons per section: AT1-L, 24+/-5; VP, 26+/-5; OXY, 11+/-2; NADPH-d, 22+/-4. Control animals had few activated PVN neurons per section. For each of the chemically identified populations of PVN neurons, the following proportions were activated: AT1-L, 12.5%; VP, 15.2%; OXY, 7.2%; NADPH-d, 17.3%. The results suggest that PVN neurons producing the AT1 receptor, VP, OXY, and NO, participate in the mediation of the central responses to circulating AII.
 ...
PMID:Activation by systemic angiotensin II of neurochemically identified neurons in rat hypothalamic paraventricular nucleus. 968 48

In the present study, we investigated the expression pattern of the inducible transcription factors (ITF) c-Fos, c-Jun, JunB, JunD, and Krox-24 following intracerebroventricular injections of hyperosmolar saline (0.2, 0.3, and 0.6 M NaCl) and its mediation via angiotensin and/or muscarinic receptors. c-Fos, c-Jun, and Krox-24 were differentially expressed in organum vasculosum laminae terminalis, median preoptic area, subfornical organ (SFO), and paraventricular and supraoptic nuclei. Expression of c-Fos and c-Jun was inhibited by pretreatment with the angiotensin AT1 receptor antagonist losartan (10 and 20 nmol icv) following 0.20 and 0.30 M saline. Pretreatment with atropine (15 nmol icv) inhibited the 0.30 and 0.60 M NaCl-induced expression of c-Fos, c-Jun, and Krox-24 in all areas except the SFO. Coexpression of the ITF with vasopressin and oxytocin, the major effector peptides in osmoregulation, was demonstrated, implying the corresponding genes as putative target genes of the ITF. The results show a highly differentiated ITF expression pattern in the brain mediated by angiotensinergic and muscarinergic pathways, suggesting a finely tuned regulation of target genes.
 ...
PMID:Central angiotensin AT1 and muscarinic receptors in ITF expression on intracerebroventricular NaCl. 968 84

This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.
 ...
PMID:Arginine vasopressin and oxytocin responses to angiotensin II are mediated by AT1 receptor subtype in normal men. 971 80

The neuropeptides angiotensin II (AngII) and oxytocin (OT) play important but opposing roles in the regulation of sodium appetite in the rat, AngII as a stimulatory peptide and OT as an inhibitory peptide. Adrenal steroids increase the density of AngII receptors in brain following in vivo administration, although the neuroanatomical and subtype specificity have not been thoroughly examined. Furthermore, previous studies demonstrate that adrenalectomy (ADX) leads to a reduction in OT receptors, although regions associated with sodium appetite remain to be examined. In the present study, quantitative receptor autoradiography was used to locate regions where perturbations in circulating adrenal steroids affect the density of oxytocin receptors and the angiotensin receptor subtypes AT1 and AT2. The results show that ADX results in a small, but significant decrease in AT1 expression in the paraventricular nucleus of the hypothalamus, subfornical organ, and the area postrema. That this effect is reversed by either aldosterone or low-dose corticosterone replacement suggests that occupancy of the mineralocorticoid receptor is responsible for the steroid effect. No changes were observed in AT2 or OT receptors in nuclei associated with sodium appetite, indicating that perturbations in adrenal steroids did not affect these receptors in brain regions implicated in the control of salt appetite.
 ...
PMID:Adrenal steroid regulation of central angiotensin II receptor subtypes and oxytocin receptors in rat brain. 975 19

Angiotensin-(1-7) (Ang-(1-7)) increased osmotic water permeability in the isolated toad skin, a tissue with functional properties similar to those of the distal mammalian nephron. Concentrations of 0.1 to 10 microM were effective, with a peak at 20 min. This effect was similar in magnitude to that of frog skin angiotensin II (Ang II) and oxytocin but lower than that of human Ang II and arginine-vasotocin. The AT2 angiotensin receptor antagonist PD 123319 (1.0 microM) fully inhibited the response to 0.1 microM Ang-(1-7) but had no effect on the response to Ang II at the same concentration. The specific receptor antagonist of Ang-(1-7), A-779, was ineffective in blocking the response to Ang-(1-7) and to frog skin Ang II. The AT1 receptor subtype antagonist losartan, which blocked the response to frog skin Ang II, was ineffective in blocking the response to Ang-(1-7). The present results support the view of an antidiuretic action of Ang-(1-7) in the mammalian nephron.
 ...
PMID:Angiotensin-(1-7) increases osmotic water permeability in isolated toad skin. 1097 45

Although the presence of endometrial receptors for angiotensin (Ang) II has been demonstrated, a specific function for AngII in the uterus has not been identified. Cytosolic free Ca2+ concentration [Ca2+]i, phospholipase C (PLC) activity and prostaglandin (PG) F2alpha secretion in response to AngII and oxytocin (OT) were measured in pig endometrial stromal cells collected 16 days after oestrus. Treatment with 100 nM OT or AngII increased (P<0.001) [Ca2+]i in stromal cells similarly (720 +/- 34 v. 690 +/- 33 pM, respectively). Subsequent administration of OT or AngII to the same cells induced smaller [Ca2+]i increases (25% or 35% of the initial responses, respectively) that occurred only if the second exposure to the same agent took place at least 5 min after the first. When administered sequentially, OT and AngII each induced a full response within 1 min of the previous treatment, regardless of which peptide was applied first. Whereas OT increased PLC activity and PGF2alpha secretion in stromal cells (P<0.01), AngII did not increase either PLC activity or PGF2alpha secretion. Type I AngII (AT1) receptors were present on stromal cells, whereas AT2 receptors were absent. Therefore, the effect of AngII in stromal cells was mediated via AT1 receptors. That AngII increased [Ca2+]i in stromal cells, but did not increase PLC or PGF2alpha secretion, indicates that either AngII releases a pool of Ca2+ through a mechanism that is not mediated by PLC and is not involved in PGF2alpha secretion or that a mechanism for PGF2alpha production other than one involving Ca2+ may exist.
 ...
PMID:Angiotensin II increases intracellular calcium concentration in pig endometrial stromal cells through type 1 angiotensin receptors, but does not stimulate phospholipase C activity or prostaglandin F2alpha secretion. 1221 42


1 2 Next >>