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)

The neurohypophysial nonapeptides vasotocin (VT) and mesotocin (MT) are the amphibian counterparts of arginine vasopressin (AVP) and oxytocin (OT). We have here reported the cloning and functional characterization of the receptors for vasotocin (VTR) and mesotocin (MTR) in two species of frog, Rana catesbeiana and Rana esculenta. The frog VTR and MTR cDNAs encode proteins of 419 and 384 amino acids respectively. Frog VTR exhibits a high degree of sequence identity with the mammalian AVP-1a (V1a) receptor while the frog MTR possesses a high degree of sequence identity with the mammalian OT receptor. Activation of VTR induced both c-fos promoter- and cAMP-responsive element (CRE)-driven transcriptional activities, while activation of MTR induced c-fos promoter-driven transcriptional activity but failed to evoke CRE-driven transcriptional activity, suggesting differential G protein coupling between VTR and MTR. The VTR exhibited the highest sensitivity for VT followed by OT>AVP approximately MT, whereas the MTR showed preferential ligand sensitivity for MT>OT>VT>AVP. A V1a agonist but not V2 and OT agonists substantially activated both VTR and MTR with a similar sensitivity. V1a, V2 and OT antagonists inhibited MT-induced MTR activation but not VT-induced VTR activation. In the frog brain, VTR and MTR mRNAs were found to be widely expressed in the telencephalon, diencephalon and mesencephalon, and exhibited very similar regional distribution. In the pituitary, VTR and MTR were expressed in the distal and intermediate lobes but were virtually absent in the neural lobe. Taken together, these data indicated that, although the distribution of VTR and MTR largely overlaps in the frog brain and pituitary, VT and MT may play distinct activities owing to the ligand selectivity and different signaling pathways activated by their receptors.
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PMID:Molecular cloning, pharmacological characterization, and histochemical distribution of frog vasotocin and mesotocin receptors. 1529 60

Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n = 10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n = 11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 mg/250 mL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.
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PMID:Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin. 1580 Mar 79

We examined the effects of intracerebroventricular (i.c.v.) administration of adrenomedullin 2 (AM2) on plasma oxytocin (OXT) and arginine vasopressin (AVP) levels in conscious rats. Plasma OXT levels were markedly increased 5 min after i.c.v. administration of AM2 (1 nmol/rat) compared with vehicle and remained elevated in samples taken at 10, 15, 30, and 60 min. By contrast, plasma AVP levels were not significantly elevated in samples taken between 5 and 180 min after i.c.v. administration of AM2 except at the 30-min time point. Fos-like immunoreactivity (Fos-LI) was observed in various brain areas, including the paraventricular (PVN) and the supraoptic nuclei (SON) after i.c.v. administration of AM2 (2 nmol/rat) in conscious rats (measured at 90 min post-AM2 infusion). Dual immunostaining for OXT/Fos and AVP/Fos showed that OXT-LI neurons predominantly exhibited nuclear Fos-LI compared with AVP-LI neurons in the PVN and the SON. In situ hybridization histochemistry showed that i.c.v. administration of AM2 (0.2, 1, and 2 nmol/rat) caused marked induction of the expression of the c-fos gene in the PVN and the SON. This induction was significantly reduced by pretreatment with both the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) (3 nmol/rat) and the AM receptor antagonist AM-(22-52) (27 nmol/rat). These results suggest that centrally administered AM2 mainly activates OXT-secreting neurons in the PVN and the SON, at least in part through the CGRP and/or AM receptors with marked elevation of plasma OXT levels in conscious rats.
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PMID:Centrally administered adrenomedullin 2 activates hypothalamic oxytocin-secreting neurons, causing elevated plasma oxytocin level in rats. 1595 53

Peripheral administration of cholecystokinin (CCK)-8 selectively activates oxytocin (OXT)-secreting neurons in the supraoptic (SON) and the paraventricular nuclei (PVN) with the elevation of plasma OXT level in rats. We examined the effects of intravenous (iv) administration of CCK-8 on the neuronal activity of hypothalamic OXT-secreting neurons and plasma OXT level in Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a congenital defect in the expression of the CCK-A receptor gene. In situ hybridization histochemistry (ISH) for c-fos mRNA revealed that the expression of the c-fos gene was not induced in the SON, the PVN, the nucleus of the tractus solitarius (NTS) and the area postrema (AP) 30 min after iv administration of CCK-8 (20 and 40 microg/kg) in OLETF rats. In Long-Evans Tokushima Otsuka (LETO) rats (controls), c-fos mRNA was detected abundantly in those nuclei 30 min after iv administration of CCK-8 (20 microg/kg). Immunohistochemistry for c-fos protein (Fos) showed that the distributions of Fos-like immunoreactivity (LI) were identical to the results obtained from ISH. Dual immunostaining for OXT and Fos revealed that Fos-LI was mainly observed in OXT-secreting neurons in the SON and the PVN of LETO rats 90 min after iv administration of CCK-8 (20 microg/kg). Radioimmunoassay for OXT and arginine vasopressin (AVP) showed that iv administration of CCK-8 did not cause significant change in the plasma OXT and AVP levels in OLETF rats, while iv administration of CCK-8 caused a significant elevation of plasma OXT level without changing the plasma AVP level in LETO rats. These results suggest that peripheral administration of CCK-8 may selectively activate the hypothalamic OXT-secreting neurons and brainstem neurons through CCK-A receptor in rats.
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PMID:Effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons in rats lacking CCK-A receptor. 1597 47

Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with ejaculation was investigated. Male Wistar rats that were pretreated with paroxetine (20 mg/kg/day p.o.) or vehicle for 22 days and had received an additional injection with the 5-HT(1A) receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.4 mg/kg s.c.) or saline on day 22, 30 min prior to a sexual behavior test, were perfused 1 h after the sexual behavior test. Brains were processed for Fos-, and oxytocin immunohistochemistry. The drug treatments markedly changed both sexual behavior and the pattern and number of Fos-immunoreactive cells in the brain. Chronic pretreatment with paroxetine caused delayed ejaculation. Acute injection with 8-OH-DPAT facilitated ejaculation in vehicle-pretreated rats, notably evident in a strongly reduced intromission frequency, whereas 8-OH-DPAT had no effects in paroxetine-pretreated rats. Chronic treatment with paroxetine reduced Fos-immunoreactivity in the locus coeruleus, and prevented the increase in Fos-immunoreactive neurons induced by 8-OH-DPAT in the oxytocinergic magnocellular part of the paraventricular nucleus as well as in the locus coeruleus. Since oxytocin and noradrenalin facilitate ejaculation, the alterations in Fos-IR in these areas could connect selective serotonin reuptake inhibitor treatment and 5-HT(1A) receptor activation to ejaculation. Chronic paroxetine treatment and 8-OH-DPAT changed c-fos expression in a number of other brain areas, indicating that Fos-immunohistochemistry is a useful tool to find locations where selective serotonin reuptake inhibitors and 8-OH-DPAT exert their effects.
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PMID:Effects of chronic paroxetine pretreatment on (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin induced c-fos expression following sexual behavior. 1601 52

Following refeeding, c-fos expression is induced in a particular set of brain regions that include the nucleus of the solitary tract (NTS), parabrachial nucleus (PB), central amygdala (CeA), paraventricular hypothalamic nucleus (PVH), supraoptic nucleus (SON) and the circumventricular organs. Within the PVH, the expression is particularly intense in the magnocellular division of the nucleus and it is as yet not clear how this activation occurs. The respective contribution of the vagus afferents and lamina terminalis, which conveys signals entering the brain through the forebrain circumventricular organs, has been investigated in rats subjected to a unilateral cervical vagotomy (UCV) or a unilateral lesion of the fibres running within the lamina terminalis (ULT) and projecting to the neuroendocrine hypothalamus. UCV significantly decreased postprandial c-fos expression in the NTS, PB, CeA and parvocellular division of the PVH. In contrast, ULT impaired postprandial activation of the magnocellular neurons in the PVH and SON. The present study also characterized the types of neurons activated in the PVH and SON during refeeding. In the magnocellular regions, arginine-vasopressin (AVP) neurons were activated upon refeeding whereas there was no apparent induction of Fos expression in oxytocin cells. In the parvocellular PVH, postprandial Fos was induced only in 30% of the corticotrophin-releasing factor (CRF) and AVP neurons. The results of the present study suggest that the postprandial activation of the brain requires the integrity of both the vagal- and lamina terminalis-associated pathways.
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PMID:Contribution of the vagus nerve and lamina terminalis to brain activation induced by refeeding. 1619 Sep 2

It has been well known that oxytocin (OT)-ergic and arginine vasopressin (AVP)-ergic neurons located in the hypothalamic paraventricular nucleus (PVN) and super optic nucleus (SON) are two kinds of neuroendocrine cells with diverse functions. It has also been demonstrated that immune stimuli can activate these neurons to secret OT and AVP. However, the intracellular signal transduction molecules responsible for the activation of these OT-ergic and AVP-ergic neurons in PVN by immune stimuli are still unclear. In this experiment, the roles of Fos, a protein product of immediate early gene c-fos, and extracellular signal-regulated protein kinase (ERK) 1/2, a signal transduction molecule of mitogen-activated protein kinase (MAPK) family, in these processes were studied in the PVN of the rat following IL-1beta stimulation. The Sprague-Dawley rats were received either 750 ng/kg IL-1beta or equal volume normal saline (NS) injection intravenously (i.v.), and perfused transcardially by 4% paraformaldehyde 3h later. Fos and phosphorylated ERK1/2 (pERK1/2)-immunoreactivity (-ir) was observed in PVN by ABC immunohistochemical staining. Meanwhile, the double staining for OT/Fos, AVP/Fos, OT/pERK1/2 and AVP/pERK1/2 were also processed. The ABC immunohistochemical staining results showed that after an i.v. injection of IL-1beta, the expressions of Fos and pERK1/2 increased evidently in the PVN. Double-staining results showed that a large number of OT-ir cells contained strong Fos-ir products in their nuclei, while only a few of OT cells were double labeled with pERK1/2. As to AVP neurons, great quantities of AVP cells were strongly double labeled with pERK1/2 while there were nearly no Fos-ir nuclei in AVP-ir cells. We conclude from these results that the intracellular IL-1beta-induced events in OT and AVP neurons in PVN are quite different. The OT neurons are mainly activated via Fos without involvement of ERK1/2 pathway, while the latter, but not Fos, involves the intracellular event in AVP neurons activated by IL-1beta.
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PMID:Different signaling molecules responsible for IL-1beta-induced oxytocinergic and vasopressinergic neuron activation in the hypothalamic paraventricular nucleus of the rat. 1638 22

Intracerebroventricular administration of oxytocin reduces anxiety behavior and hypothalamo-pituitary-adrenal (HPA) responses to stress in female rats. Similar changes are seen in late-pregnant rats, and oxytocin-sensitive pathways may mediate these effects. This study investigated anxiety behavior and stress responses using a gonadal steroid model of late pregnancy, which is known to increase endogenous oxytocin expression. Compared with continuous progesterone treatment, 3-d withdrawal of progesterone after 11-d treatment of ovariectomized rats with estradiol and progesterone resulted in increased binding of the oxytocin receptor ligand [(125)I]d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2)(9)]ornithine vasotocin in selective forebrain regions, including the ventrolateral septum and ventromedial hypothalamus. Behavior in the elevated plus-maze indicated that progesterone withdrawal had an anxiolytic effect, and this was associated with lower levels of c-fos mRNA expression in the ventral hippocampus, an area previously shown to be sensitive to oxytocin. In other groups of animals, the plasma corticosterone response to a psychological stress (10 min of 114 dB white noise) was significantly attenuated by this steroid manipulation. Furthermore, simultaneous infusion of the selective oxytocin receptor antagonist desGlyNH(2), d(CH(2))(5)[Tyr(Me)(2),Thr(4)]OVT during the period of progesterone withdrawal reversed this attenuation of noise-induced HPA activation, indicating a role for endogenous oxytocin in this effect. Thus, mimicking the steroid profile of late pregnancy leads to a reduction in anxiety behavior and attenuates HPA activity induced by mild stress. These effects appear to be mediated through the involvement of central oxytocin neurotransmission.
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PMID:Gonadal steroid modulation of stress-induced hypothalamo-pituitary-adrenal activity and anxiety behavior: role of central oxytocin. 1643 58

During the early phase of endotoxic shock the hypothalamus is activated and neurohypophyseal hormone secretion is increased. In order to study the participation of the subfornical organ (SFO) in this response we lesioned the nucleus and determined hormone secretion and c-fos expression in the paraventricular and supraoptic nuclei after administration of lipopolysaccharides (LPS) in rats. LPS significantly increased the number of cells showing Fos immunoreactivity in the paraventricular and supraoptic nuclei of the hypothalamus (p < 0.05) and also caused an increase in plasma levels of vasopressin and oxytocin (p < 0.05). SFO lesion significantly reduced LPS-induced Fos immunoreactivity (p < 0.05) and hormone secretion (p < 0.05). We conclude that the SFO participates in the activation of the hypothalamic-neurohypophyseal axis in the early phase of endotoxic shock.
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PMID:Participation of the subfornical nucleus in hypothalamic-neurohypophyseal axis activation during the early phase of endotoxic shock. 1681 33

We examined the effects of i.c.v. administration of neuro-peptide W-30 (NPW30) on plasma arginine vasopressin (AVP) and plasma oxytocin (OXT) using RIA. The induction of c-fos mRNA, AVP heteronuclear (hn)RNA, and c-Fos protein (Fos) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of rats were also investigated using in situ hybridization histochemistry for c-fos mRNA and AVP hnRNA, and immunohistochemistry for Fos. Both plasma AVP and OXT were significantly increased at 5 and 15 min after i.c.v. administration of NPW30 (2.8 nmol/rat). In situ hybridization histochemistry revealed that the induction of c-fos mRNA and AVP hnRNA in the SON and PVN were significantly increased 15, 30, and 60 min after i.c.v. administration of NPW30 (1.4 nmol/rat). Dual immunostaining for Fos/AVP and Fos/OXT revealed that both AVP-like immunoreactive (LI) cells and OXT-LI cells exhibited nuclear Fos-LI in the SON and PVN, 90 min after i.c.v. administration of NPW30 (2.8 nmol/rat). These results suggest that central NPW30 may be involved in the regulation of secretion of AVP and OXT in the magnocellular neurosecretory cells in the SON and PVN.
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PMID:Centrally administered neuropeptide W-30 activates magnocellular neurosecretory cells in the supraoptic and paraventricular nuclei with neurosecretion in rats. 1689 56


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