Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P01178 (oxytocin)
15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurohypophyseal oxytocin (OT), secreted continuously under conditions of hyperosmolality, is a potent natriuretic hormone in rats. In contrast, OT secretion during lactation is pulsatile and is not accompanied by increased urinary Na+ excretion. The present experiments compared the effects of continuous and pulsatile infusion of OT on natriuresis in rats. In male rats anesthetized with Inactin, continuous infusion of OT (125 ng/kg x h) increased plasma OT to about 70 pg/ml; renal Na+ excretion increased 10-fold, and urine volume and K+ excretion also were elevated. However, when OT was administered i.v. in the same amount but in pulses given once every 5 or 10 min, to simulate the pattern of OT secretion during lactation, rats did not excrete significantly more urine, Na+, or K+ than did vehicle-treated animals. The plasma renin concentration, measured in these experiments because OT receptors are present in the macula densa, increased 2-fold when OT was infused either continuously or in pulses. These results indicate that the effects of OT administration on urinary Na+ excretion in rats varies depending on whether the infusion is pulsatile or continuous, whereas the effects of OT on renin secretion show no such difference.
...
PMID:Sodium excretion and renin secretion after continuous versus pulsatile infusion of oxytocin in rats. 1034 72

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in alpha2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.
...
PMID:Selective serotonin reuptake inhibitors and neuroendocrine function. 1050 38

Arterial hypotension and hypovolemia are known to stimulate neurohypophysial secretion of oxytocin (OT) in rats, although the physiological function of OT under these circumstances is uncertain. We now report that OT infused intravenously into conscious rats at 125 ng x kg(-1) x h(-1), a dose selected to mimic plasma OT levels during hypotension or hypovolemia, increased plasma renin concentration and plasma renin activity by twofold. This effect was prevented by systemic pretreatment with an OT receptor antagonist [[1-(3-mercaptopropionic acid)-2-O-ethyl-D-Tyr-Thr(4)-Orn(8)]-OT]. The OT antagonist did not block renin secretion induced by systemic injection of the beta-adrenergic receptor agonist isoproterenol, indicating that the OT antagonist does not interfere nonselectively with renin release. Pretreatment of rats with the beta-adrenergic receptor antagonist nadolol also prevented OT-induced renin secretion. Similarly, nadolol injected during infusion of OT markedly reduced the elevated plasma renin levels. These observations raise the possibility that pituitary OT secretion during hypotension or hypovolemia in rats may serve to support blood pressure by enhancing activation of the renin-angiotensin system via a beta-adrenergic receptor-dependent mechanism.
...
PMID:Oxytocin-induced renin secretion in conscious rats. 1064 43

The aim of the present study was to investigate the anxiolytic effects of long-term treatment with fluoxetine in rats. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic disorders, in addition to treating depression. A major concern with SSRIs is a 2-3-week delay in their therapeutic effects. SSRIs share with anxiolytic 5-HT(1A) agonists the ability to produce desensitization of post-synaptic 5-HT(1A) receptors. To investigate the anxiolytic effects of fluoxetine, rats were treated for 14 days with fluoxetine (10 mg kg(-1) day(-1), i.p. ). The rats were stressed using a conditioned stress procedure and tested one day after the last fluoxetine injection. Fluoxetine decreased stress-induced defecation (by 60%), reversed the stress-induced suppression of exploring behavior (by 59%) and shortened the duration of stress-induced freezing behavior (by 11. 5%). However, the stress-induced increase in plasma levels of ACTH, corticosterone, oxytocin, prolactin and renin were not inhibited by fluoxetine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mechanism of the anxiolytic effects of fluoxetine. In contrast, the neuroendocrine responses to conditioned stress are not affected by these neuroadaptive changes.
...
PMID:Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats. 1065 Jan 30

Previous experiments have indicated that arterial hypotension increases plasma oxytocin (OT) levels in rats and that OT infused intravenously causes an increase in plasma renin activity (PRA). The goal of the present study was to determine whether systemic administration of an OT receptor antagonist would attenuate the increase in PRA that is normally evoked by arterial hypotension in rats. In conscious male rats, intravenous injection of hydralazine or diazoxide produced sustained hypotension and evoked a significant increase in PRA, as expected. Intravenous infusion of an OT receptor antagonist did not alter the hypotension induced by hydralazine or diazoxide, but it did markedly blunt the induced increase in PRA. The OT receptor antagonist also blunted the hypotension-evoked increase in heart rate and plasma vasopressin levels, suggesting that the antagonist may have generally disrupted afferent signaling of hypotension. Thus hypotension-evoked OT secretion may contribute to cardiovascular homeostasis by enhancing baroreceptor signals that stimulate increases in renin secretion, vasopressin secretion, and heart rate during arterial hypotension in rats.
...
PMID:Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats. 1117 55

The 5-HT(2A/2C) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) stimulates hypothalamic neurons to increase the secretion of several hormones. This study addressed two questions: 1) are the neuroendocrine effects of DOI mediated via activation of 5-HT(2A) receptors; and 2) which neurons are activated by 5-HT(2A) receptors. The 5-HT(2A) antagonist (+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (MDL 100,907; 0.001, 0.01, or 0.1 mg/kg, s.c.) was administered before rats were challenged with DOI (2.5 mg/kg, i.p.). MDL 100,907 produced a dose-dependent inhibition (ED(50) congruent with 0.001 mg/kg) of the effect of DOI on plasma levels of ACTH, corticosterone, oxytocin, prolactin, and renin without altering basal hormone levels. Complete blockade of the effect of DOI was achieved for all hormones at MDL 100,907 doses of 0.01-0.1 mg/kg. In a parallel experiment, DOI was injected 2 hr before killing to determine its effects on the expression of Fos, the product of the immediate early gene c-fos. DOI induced an increase in Fos immunoreactivity in corticotropin-releasing factor (CRF) and in oxytocin-expressing neurons but not in vasopressin-containing neurons in the hypothalamic paraventricular nucleus or CRF cells in the amygdala. Pretreatment with MDL 100,907 (0.1 mg/kg, s.c.) blocked the DOI-induced increase in Fos expression in all regions including the hypothalamus, amygdala (central and corticomedial), bed nucleus of the stria terminalis, and prefrontal cortical regions. The combined neuroanatomical and pharmacological observations suggest that the neuroendocrine responses to DOI are mediated by activation of neurons in the hypothalamic paraventricular nucleus and associated circuitry. Furthermore, selective activation of 5-HT(2A) receptors mediates the hormonal and Fos-inducing effects of DOI.
...
PMID:5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells. 1133 86

Although women constitute the majority of patients who receive treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, most animal studies of SSRIs are conducted on males. The present study investigated whether long-term treatment of cycling female rats with fluoxetine alters their estrous cycle and the sensitivity of hypothalamic serotonin (5-HT) 5-HT(1A) and 5-HT(2A) receptor systems. Adult female rats received daily injections of fluoxetine (10 mg/kg, i.p.) for three consecutive estrous cycles (15.2+/-0.2 days) with the first injection beginning on metestrus (when circulating estrogen levels are low and stable). Fluoxetine did not alter basal plasma estradiol levels at metestrus, nor did it alter the pattern of estrous cyclicity. Rats treated with fluoxetine showed a loss in body weight. On the morning of metestrus of the fourth cycle (18 h after the last fluoxetine injection), the rats were injected with a sub-maximal dose of the 5-HT(1A) agonist (+/-)-8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT, 50 MICRO/kg, s.c.) or a maximal dose of the 5-HT(2A) agonist [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] (DOI). Plasma levels of oxytocin, ACTH and corticosterone were measured as peripheral indicators of hypothalamic 5-HT(1A) and 5-HT(2A) receptor sensitivity. Injecting 8-OH-DPAT to saline pretreated rats produced a significant increase in plasma oxytocin (299%), ACTH (1456%) and corticosterone (170%) levels but not in plasma prolactin or renin concentrations. Greater increases in plasma levels of these hormones were observed after injecting DOI. Fluoxetine treatment completely blocked the oxytocin, ACTH and corticosterone responses to 8-OH-DPAT, but did not inhibit the effect of DOI on any hormone, thus confirming that fluoxetine treatment did not produce a deficit in the functioning of corticotropin releasing hormone or oxytocin containing neurons. These results indicate that in cycling female rats, fluoxetine treatment desensitizes hypothalamic post-synaptic 5-HT(1A) receptor signaling. Understanding the pharmacological effects of fluoxetine in females may lead to more effective treatment of women with mood disorders.
...
PMID:Treatment of cycling female rats with fluoxetine induces desensitization of hypothalamic 5-HT(1A) receptors with no change in 5-HT(2A) receptors. 1221 58

The present study determined whether the serotonin2A (5-HT2A) receptors in the hypothalamic paraventricular nucleus mediate the neuroendocrine responses to a peripheral injection of the 5-HT2A/2C receptor agonist (-)DOI [(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The 5-HT2A receptor antagonist MDL100,907 ((+/-)-alpha(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol), the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), or vehicle were microinjected bilaterally through a chronically implanted double-barreled cannula into the hypothalamic paraventricular nucleus 15 min before a peripheral injection of (-)DOI in conscious rats. (-)DOI significantly elevated plasma levels of oxytocin, prolactin, ACTH, corticosterone, and renin. Neither the 5-HT2A receptor antagonist nor the 5-HT2C receptor antagonist, injected alone, altered the basal levels of these hormones. MDL100,907 (0.748, 7.48, and 18.7 nmol) dose dependently inhibited the (-)DOI-induced increase in all of the hormones except corticosterone. In contrast, SB-242084 (10 nmol) did not inhibit (-)DOI-increased hormone levels. To confirm the presence of 5-HT2A receptors in the hypothalamic paraventricular nucleus, 5-HT2A receptors were mapped using immunohistochemistry. Densely labeled magnocellular neurons were observed throughout the anterior and posterior magnocellular subdivisions of the hypothalamic paraventricular nucleus. Moderately to densely labeled cells were also observed in parvicellular regions. Thus, it is likely that 5-HT2A receptors are present on neuroendocrine cells in the hypothalamic paraventricular nucleus. These data provide the first direct evidence that neuroendocrine responses to a peripheral injection of (-)DOI are predominantly mediated by activation of 5-HT2A receptors in the hypothalamic paraventricular nucleus.
...
PMID:Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI. 1241 89

The effects of oxytocin on renin secretion by denervated kidney were investigated in vivo, by infusing the peptide directly into the renal artery of anaesthetized rats. Renin secretion was calculated by the renal veno-arterial difference in plasma renin activity multiplied by renal plasma flow. The intra-renal arterial (i.r.a.) infusion of oxytocin (1.5 or 15 ng/kg/min, 10 min) induced a sixfold increase in renin secretion as compared to vehicle-treated controls, without effects on renal blood flow, mean arterial blood pressure, glomerular filtration rate or natriuresis. The effect of oxytocin (1.5 ng/kg/min) was prevented by pretreatment with an oxytocin receptor antagonist, desGly-NH(2),d(CH(2))(5)[D-Tyr(2),Thr(4),Orn(8)]vasotocin] (5.6 microg/kg bolus i.v. 20 min before oxytocin infusion, followed by 2.8 microg/kg/min i.r.a.). Nadolol (2.5 mg/kg i.v.), a beta-adrenoceptor antagonist, also blocked the oxytocin-induced increase in renin secretion. These results show that oxytocin is able to stimulate renin release by activating oxytocin receptors but that beta-adrenoceptors also seem to be involved.
...
PMID:Oxytocin-induced renin secretion by denervated kidney in anaesthetized rat. 1242 53

Our recent published studies suggest that angiotensin II (AII), generated and retained intracellularly, enhances growth of H4-II-E-C3 rat hepatoma cells, an average of 33%. Proliferation conferred by introduction of a plasmid [ Ang(-S)Exp/pSVL ] encoding a signal sequence-depleted angiotensinogen [Ang(-S)Exp] into these cells (which we have shown possess ACE and renin mRNAs) is mediated, at least in part, by enhanced PDGF-A chain mRNA production and protein secretion. The mitogenic effect is inhibited by losartan suggesting that it involves AII interaction with an AT(1)-like receptor. Introduction of anti-AII antibodies into the medium of these transfected cells has no effect upon growth of the cells, suggesting that AII is retained by the cells and that intracellular AII is growth stimulatory. In the present study, we sought to further characterize the intracellular localization and mode of action of Ang(-S)Exp. Consistent with our expectations, we now show that a fusion product of Ang(-S)Exp with green fluorescent protein [Ang(-S)Exp/EGFP], generated from an expression plasmid, is abundant and primarily cytoplasmic. Wild-type angiotensinogen/EGFP, in contrast, is only detectable following a cold-block (which acts to enhance folding-kinetics and slow secretion) and is largely restricted to the secretory pathway. We further show, using semi-quantitative RT/PCR that the long isoform of PDGF mRNA is elevated in Ang(-S)Exp transfected cells and in AII-treated naive cells but not in losartan-treated Ang(-S)Exp transfected cells. We identify C-terminal amidation recognition sites within the long-form protein (that are not present in the short-form) and show that these cells possess PAM (amidating enzyme precursor) and carboxypeptidase E mRNAs (the corresponding proteins of which are sufficient for amidation). Inhibitors of amidation inhibit growth of naive and Ang(-S)Cntr/ pSVL -transfected cells (2.6-fold for phenylbutenoic acid and 3.5-fold for disulfiram treatment) but more profoundly inhibit growth of Ang(-S)Exp/pSVL -transfected cells (6.7-fold for phenylbutenoic acid and 13-fold for disulfiram). In conclusion, these data confirm that signal sequence-depleted Ang(-S)Exp is retained within cells and is largely cytoplasmic. Because C-terminal amidation is absolutely required for full biological potency of a number of peptide hormones (including oxytocin, gastrin and calcitonin), we postulate that growth effects of both intracellular AII and exogenous AII can be conferred by PDGF long-form, possibly through an amidation-dependent mechanism.
...
PMID:Intracellular angiotensin II increases the long isoform of PDGF mRNA in rat hepatoma cells. 1243 51


<< Previous 1 2 3 4 5 6 7 8 Next >>

---