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 effect of angiotensin II and [Sar1,Ile5,Ala8]-angiotensin II on uterine contractions and the relationship of uterine prostaglandins to these effects were studied. Uterine segments from pregnant rats were monitored in vitro for isometric contractile activity in Krebs-Ringer medium (95% O2-5% CO2; 37 C). The medium was sampled periodically and assayed for prostaglandin E2, prostaglandin F2 alpha, and 13,14-dihydro-15-keto-prostaglandin F2 alpha by RIA. Angiotensin II increased frequency of contractions and integrated contractile force in a dose-related fashion. Angiotensin II (1 microgram) resulted in increased prostaglandin (PG) production, but there was no clear dose-related effect. Indomethacin significantly reduced PG production (P < 0.001); however, the contractile response to angiotensin II was not affected. [Sar1,Ile5,Ala8]Angiotensin II had no effect on spontaneous contractile activity or PG production in uteri from 18 or 21 days of pregnancy, nor did [Sar1,Ile5,Ala8]angiotensin II affect oxytocin-stimulated uterine contractions. [Sar1,Ile5,Ala8]Angiotensin II (2.5 microgram) did inhibit (P < 0.05) uterine contractions induced by angiotensin II (0.5 microgram), but PG production was not affected. In conclusion, the studies described provide evidence that angiotensin II-induced uterine contractions of in vitro pregnant rat uteri are not dependent upon increased PG production.
 ...
PMID:Angiotensin II and [Sar1, Ile5, Ala8]angiotensin II effect on contractile activity and prostaglandin production of in vitro pregnant rat uteri. 742 93

These studies evaluated the involvement of central oxytocin (OT) and atrial natriuretic peptide (ANP) receptors in the osmotic inhibition of hypovolemia-induced salt appetite. Rats were pretreated centrally with the A chain of the cytotoxin ricin conjugated to OT (rAOT) or ANP (rAANP) to selectively inactivate cells bearing these respective receptors, or rats were pretreated with the unconjugated A chain (rA) as a control. Hypovolemia was induced with subcutaneous colloid injections, and rats then were given either 2 M mannitol, which raises plasma osmolality but lowers plasma sodium, or 1 M NaCl, which raises both. Hypertonic mannitol inhibited saline ingestion in rA-treated control rats but stimulated ingestion in rAOT- and rAANP-treated rats, whereas hypertonic NaCl blunted saline ingestion in rA- and rAOT-treated rats but stimulated ingestion in rAANP-treated rats. Angiotensin II-induced saline intake was similarly potentiated in rAOT- and rAANP-treated rats, indicating that this treatment also activates central inhibitory OT and ANP pathways. These data suggest that central ANP receptors mediate both Na(+)- and osmolality-induced inhibition of NaCl ingestion, whereas central OT receptors primarily mediate osmolality-induced inhibition of NaCl ingestion in rats.
 ...
PMID:Central oxytocin and ANP receptors mediate osmotic inhibition of salt appetite in rats. 765 44

Angiotensin II (Ang) injected intracerebroventricularly stimulates neurohypophyseal vasopressin (AVP) release into the peripheral circulation. As we have shown previously, central actions of Ang II in the rat forebrain are mediated by the AT1A receptor subtype. In the present paper, we attempted to clarify the cellular localization of the AT1A receptor mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, in order to reappraise the conflicting data on the nature of the angiotensin II receptor involved in Ang induced vasopressin release. For this purpose, double in situ hybridization was performed using a radioactive AT1A receptor riboprobe and a digoxygenin labeled AVP oligoprobe, and immunohistochemical localization of the glial marker glial fibrillary acidic protein (GFAP) on the same brain slice. The results show neuronal expression of AT1A receptor mRNA mainly in dorsal and medial parvocellular parts of the PVN, its localization in some magnocellular PVN neurons and the absence of its expression in AVP producing neurons either in the PVN or in the SON. Thus, while indirect evidence indicates the involvement of the AT1A receptor subtype in the regulation of CRH and oxytocin release, the stimulation of vasopressinergic neurons is likely due to indirect mechanisms, or to a yet unknown type of angiotensin receptor.
 ...
PMID:Comparative expression of vasopressin and angiotensin type-1 receptor mRNA in rat hypothalamic nuclei: a double in situ hybridization study. 875 Aug 69

Prolyl endopeptidase has been predominantly described as a cytosolic activity capable of cleaving a number of important neuropeptides (including TRH, LHRH, Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on the carboxy side of proline. In this paper, we report, for the first time, on the complete purification and characterization of a membrane-bound form of prolyl endopeptidase. This novel activity has been isolated from the synaptosomal (plasma membranes) membranes of bovine brain. Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity. The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60 microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme demonstrated a relatively broad substrate specificity and a relatively high affinity for proline-containing neuropeptides. It was shown to be inhibited by certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline, thus possibly classifying it as a 'thimet' activity. The purified particular form of proyl endopeptidase displayed a similar substrate specificity to the previously reported cytosolic forms of the enzyme. However, there were differences between the two forms in term of their sensitivity to inhibitors, their affinities for the peptide substrates and their relative molecular masses. The different subcellular location (i.e. the synaptosomal membrane) of the particulate prolyl endopeptidase is also of potential physiological significance given that here it is more likely to come in contact with the vesicle-bound neuropeptides than is its cytosolic counterpart.
 ...
PMID:Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain. 902 55

This review examines recent advances in the study of the behavioral responses to deficits of body water and body sodium that in humans are accompanied by the sensations of thirst and salt appetite. Thirst and salt appetite are satisfied by ingesting water and salty substances. These behavioral responses to losses of body fluids, together with reflex endocrine and neural responses, are critical for reestablishing homeostasis. Like their endocrine and neural counterparts, these behaviors are under the control of both excitatory and inhibitory influences arising from changes in osmolality, endocrine factors such as angiotensin and aldosterone, and neural signals from low and high pressure baroreceptors. The excitatory and inhibitory influences reaching the brain require the integrative capacity of a neural network which includes the structures of the lamina terminalis, the amygdala, the perifornical area, and the paraventricular nucleus in the forebrain, and the lateral parabrachial nucleus (LPBN), the nucleus tractus solitarius (NTS), and the area postrema in the hindbrain. These regions are discussed in terms of their roles in receiving afferent sensory input and in processing information related to hydromineral balance. Osmoreceptors controlling thirst are located in systemic viscera and in central structures that lack the blood-brain barrier. Angiotensin and aldosterone act on and through structures of the lamina terminalis and the amygdala to stimulate thirst and sodium appetite under conditions of hypovolemia. The NTS and LPBN receive neural signals from baroreceptors and are responsible for inhibiting the ingestion of fluids under conditions of increased volume and pressure and for stimulating thirst under conditions of hypovolemia and hypotension. The interplay of multiple facilitory influences within the brain may take the form of interactions between descending angiotensinergic systems originating in the forebrain and ascending adrenergic systems emanating from the hindbrain. Oxytocin and serotonin are additional candidate neurochemicals with postulated inhibitory central actions and with essential roles in the overall integration of sensory input within the neural network devoted to maintaining hydromineral balance.
 ...
PMID:The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms of central integration. 923 80

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

Angiotensin II and atrial natriuretic peptide (ANP) play important and opposite roles in the control of water and salt intake, with angiotensin II promoting the intake of both and ANP inhibiting the intake of both. Following blood volume expansion, baroreceptor input to the brainstem induces the release of ANP within the hypothalamus that releases oxytocin (OT) that acts on its receptors in the heart to cause the release of ANP. ANP activates guanylyl cyclase that converts guanosine triphosphate into cyclic guanosine monophosphate (cGMP). cGMP activates protein kinase G that reduces heart rate and force of contraction, decreasing cardiac output. ANP acts similarly to induce vasodilation. The intrinsic OT system in the heart and vascular system augments the effects of circulating OT to cause a rapid reduction in effective circulating blood volume. Furthermore, natriuresis is rapidly induced by the action of ANP on its tubular guanylyl cyclase receptors, resulting in the production of cGMP that closes Na+ channels. The OT released by volume expansion also acts on its tubular receptors to activate nitric oxide synthase. The nitric oxide released activates guanylyl cyclase leading to the production of cGMP that also closes Na+ channels, thereby augmenting the natriuretic effect of ANP. The natriuresis induced by cGMP finally causes blood volume to return to normal. At the same time, the ANP released acts centrally to decrease water and salt intake.
 ...
PMID:Neuroendocrine control of body fluid homeostasis. 1256 18

To explore the role of oxytocin in the regulation of salt appetite and blood pressure, we conducted studies in oxytocin gene-knockout mice and determined (1) blood pressure and heart rate during day and night periods, (2) salt appetite after iso-osmotic volume depletion, and (3) salt appetite and blood pressure after central injection of angiotensin II. Long-term arterial catheters were inserted, and blood pressure and heart rate were recorded for 24 hours. There was a modest decrease in blood pressure and heart rate in knockout mice. Salt appetite was measured with a 2- bottle choice (water and 2% NaCl), with measurement of licking activity. Mice were injected subcutaneously with 30% polyethylene glycol (0.5 mL), and voluntary intakes were measured for 24 hours. Knockout mice consumed 3 times the amount of NaCl than did controls, 276+/-77 vs 90+/-38 licks/24 h (P<0.05). Water consumption was similar between groups. Angiotensin II (5, 50, and 200 ng/3 microL) injected intracerebroventricularly produced dose-related increases in intake, with no differences between the groups. The 50-ng dose of angiotensin II elicited salt and water intakes of 151+/-43 vs 160+/-33 licks and 250+/-53 vs and 200+/-51 licks, respectively (control vs knockout). The pressor response to angiotensin II was not different between the groups. Results suggest that oxytocin plays a role in the regulation of blood pressure and salt appetite, specifically as mediated by volume receptors, and that the renin-angiotensin system is not involved in these changes.
 ...
PMID:Salt appetite and the renin-angiotensin system: effect of oxytocin deficiency. 1295 13

Mammals control the volume and osmolality of their body fluids from stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+ receptors and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrated response, which depends on the integrity of the anteroventral region of the third ventricle, e.g., organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. The hypothalamo-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and nonosmotic stimuli. Since the discovery of the atrial natriuretic peptide (ANP), a large number of publications have demonstrated that this peptide provides a potent defense mechanism against volume overload in mammals, including humans. ANP is mostly localized in the heart, but ANP and its receptor are also found in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation. Blood volume expansion acts not only directly on the heart, by stretch of atrial myocytes to increase the release of ANP, but also on the brain ANPergic neurons through afferent inputs from baroreceptors. Angiotensin II also plays an important role in the regulation of body fluids, being a potent inducer of thirst and, in general, antagonizes the actions of ANP. This review emphasizes the role played by brain ANP and its interaction with neurohypophysial hormones in the control of body fluid homeostasis.
 ...
PMID:Neuroendocrine control of body fluid metabolism. 1471 14

Angiotensin II (50 ng/5 microl) and L-NAME (250 microg/5 microl), an inhibitor of NO synthase (NOS), were administered intracerebroventricularly alone or in combination to conscious rats. Mean arterial blood pressure (MABP) increased reaching a peak within 5 min in all groups compared to controls treated with the vehicle, artificial CSF (5 microl). MABP returned to basal levels at 30 min after angiotensin II and remained stable for the following 90 min. In animals treated with L-NAME alone, after the initial pressor response, MABP declined but began to increase progressively from 30 min until the end of the experiment at 120 min. When administered with angiotensin II, however, the initial pressor response was prolonged. Angiotensin II-induced drinking was significantly attenuated by L-NAME. In control rats, inhibiting NOS elevated plasma levels of oxytocin and vasopressin but in angiotensin II-stimulated animals, only oxytocin was further elevated after L-NAME. Thus, NO formed centrally inhibits basal secretion of oxytocin and vasopressin as well as the resting blood pressure. During stimulation with angiotensin II, NO facilitates drinking, limits the pressor response and selectively inhibits oxytocin release.
 ...
PMID:NO and angiotensin II effects on blood pressure and fluid homeostasis. 1530 73


<< Previous 1 2 3 Next >>