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)

Human placental aminopeptidase M and A and post-proline endopeptidase are known to act as degrading enzymes of bioactive peptides such as angiotensin II, oxytocin and endogenous opioids. We tested the effects of cortisol on the activities of human placental aminopeptidase A and M and post-proline endopeptidase using short-cultured placental tissues. From 34.5 nM to 3.45 microM of cortisol significantly increased the activities of 3 enzymes. Our present data suggest a possible important role of cortisol in the growth of human placenta via induction of placental aminopeptidases.
 ...
PMID:Induction by cortisol of aminopeptidases production from the human placenta in tissue culture. 134 55

Our study showed that there were statistically significant correlations between the systolic and diastolic ratio (S/D) of maternal uterine or umbilical artery and the levels of maternal serum aminopeptidase activities in pre-eclampsia. Kininase I was positively correlated with the S/D ratios, whereas placental leucine aminopeptidase (P-LAP) and aminopeptidase A were negatively correlated with the S/D ratios. It is known that the increased S/D ratios reflect the increased utero-placental blood flow resistance. Since our previous study showed that placental aminopeptidases degrade vasoactive peptides such as oxytocin, angiotensin and bradykinin, which the fetus actively produces, our present study suggests that the increased vascular resistance in feto-placental circulation in pre-eclampsia is partly controlled by changes in vaso-active peptides, via degradation by placental aminopeptidases.
 ...
PMID:Relationship between the changes in placental blood flow resistance assessed by Doppler technique and maternal serum placental aminopeptidases, which degrade vaso-active peptides, in pre-eclampsia. 151 91

Microvilli from human placental syncytiotrophoblast are rich in angiotensin I converting enzyme (ACE), aminopeptidase A, a carboxypeptidase N-like enzyme, and a neutral endopeptidase (NEP). The specific activities of these enzymes were enhanced in microvillus-enriched fractions obtained by differential centrifugation: Purified microvilli were isolated in a discontinuous sucrose gradient. The placental microvilli hydrolyzed angiotensin II, vasopressin and oxytocin as shown by high pressure liquid chromatography. The inhibitors, bestatin, phosphoramidon, and o-phenanthroline, established the specificity of the enzymes. Aminopeptidase A (angiotensinase A) cleaved angiotensin II to angiotensin III and Asp1. NEP from placenta and from human kidney hydrolyzed oxytocin at the Pro7-Leu8 bond to yield oxytocin 1-7 and leucyl-glycine amide, but did not hydrolyze vasopressin. Vasopressin was cleaved by aminopeptidases in the placental membranes. On electroblotting placental NEP appeared as a double band with a molecular weight slightly higher than the 90,000 of the purified kidney enzyme. Neuraminidase treatment reduced the molecular weight of the placental enzyme to approximately 90,000, indicating that it contains a large amount of sialic acid. The microvilli of human placenta are thus rich in enzymes that may regulate passage of peptides at the maternal-fetal interface.
 ...
PMID:Enzymes in placental microvilli: angiotensin I converting enzyme, angiotensinase A, carboxypeptidase, and neutral endopeptidase ("enkephalinase"). 609 76

The serum level of placental leucine aminopeptidase (P-LAP) increases during pregnancy. P-LAP degrades several peptide hormones such as oxytocin and vasopresin, suggesting a role in maintaining homeostasis during pregnancy. In the study reported here, we have isolated a cDNA clone with 4084 base pairs encoding P-LAP from a human placental cDNA library. The amino acid sequence deduced from the cDNA contained all of the sequences of the peptide fragments obtained by digestion of the purified protein with trypsin. The predicted P-LAP contains the HEXXH consensus sequence of zinc metallopeptidases, indicating that the enzyme belongs to this family, which includes aminopeptidase N and aminopeptidase A. The deduced sequence also contains a hydrophobic region near the N terminus, suggesting that the enzyme is a type II integral membrane protein. Northern blot analysis revealed that P-LAP was expressed in several tissues, some of which expressed two forms of mRNAs. These results suggest that the enzyme is synthesized as an integral membrane protein and is released into blood under some physiological conditions.
 ...
PMID:Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family. 855 Jun 19

Placental leucine aminopeptidase (P-LAP)/oxytocinase (OTase) degrades several small peptides such as oxytocin (OT), arginine vasopressin (AVP) and angiotensin III (ANGIII), and aminopeptidase A (AP-A) converts angiotensin II (ANGII) to ANGIII. These proteases play an important role in foetal growth and the maintenance of human homeostasis during pregnancy. In this study, we confirmed the distribution of P-LAP and AP-A proteins and messenger RNAs in human trophoblasts in normal placenta and complete hydatidiform mole by immunohistochemical and in-situ hybridization techniques. Immunoreactivity of P-LAP was mainly noted in the apical membrane of syncytiotrophoblasts, and the expression of messenger RNA (mRNA) for P-LAP was predominantly noted in the cytoplasm of syncytiotrophoblastic cells. However, immunoreactivity of AP-A was mainly noted in the apical membrane of cytotrophoblasts and in the basal zone of the syncytiotrophoblasts, and the expression of mRNA for AP-A was predominantly noted in cytoplasm of cytotrophoblastic cells and a little in cytoplasm of syncytiotrophoblastic cells. Thereby, the two proteases were differentially distributed both in normal placenta and hydatidiform mole throughout the gestational age. These results are useful for the further understanding of not only the pathophysiology of pregnancy, but also the pathogenesis of trophoblastic diseases.
 ...
PMID:Differential distribution of placental leucine aminopeptidase/oxytocinase and aminopeptidase A in human trophoblasts of normal placenta and complete hydatidiform mole. 1236 82

Membrane-bound peptidases play a key role in the control of growth, differentiation, and signal transduction of many cellular systems by degrading bioactive peptides. Thus, abnormal changes in their expression pattern and catalytic function result in altered peptide activation, which contributes to neoplastic transformation or progression. In this review, we describe our recent findings along with work from other groups on the expression and biological functions of membrane-bound peptidases in cancer, focusing on the regulatory roles of three peptidases, aminopeptidase A (APA), neutral endopeptidase (NEP) and placental leucine aminopeptidase (P-LAP), in the progression of gynecologic malignancies. APA, NEP and P-LAP are differentially expressed and localized in various gynecologic malignancies including cervical cancer, endometrial cancer, ovarian cancer and choriocarcinoma in a tumor-type specific pattern. The expression levels are up- or down-regulated depending on histological grade or disease progression. These peptidases play regulatory roles in tumor cell proliferation, invasion or angiogenesis via degradation/inactivation of target peptides such as angiotensin II, endothelin-1 and oxytocin, which act on cancer cells as stimulatory or inhibitory factors. Thus, membrane-bound peptidases may become not only a new diagnostic/prognostic marker, but also a novel molecular target for the treatment of gynecologic malignancies.
 ...
PMID:Regulatory role of membrane-bound peptidases in the progression of gynecologic malignancies. 1544 4

Essential hypertension is one of the major contributors to premature morbidity and mortality due to the incresased risk for coronary heart disease, stroke, renal disease, peripheral vascular disease and vascular dementia for both men and women. However, its basic causes remain unknown. In the present work we studied the activity of several proteolytic regulatory enzymes related to renin-angiotensin-system (RAS) (aminopeptidase A, APA; aminopeptidase N, APN; aminopeptidase B, APB; and insulin-regulated aminopeptidase, IRAP); with oxytocin regulation (oxytocinase); with the metabolism of GnRH and TRH (pyrrolidone carboxypeptidase, Pcp); and with enkephalins metabolism (enkephalindegrading activity, EDA), to elucidate their role in the mechanisms responsible of essential hypertension and to discuss the possible gender differences. Serum samples of 53 individuals with essential hypertension and 60 healthy volunteers were collected and used to assay enzyme activities, gonad hormones testosterone and estradiol, TSH and free thyroxin (fT4). Differences were observed in APA, APN, Pcp and EDA specific activities, and in serum gonad hormone levels between hypertensive and control groups. Only Pcp activity showed gender differences. Regarding the RAS, APA is reduced while APN is increased, suggesting increased levels of angiotensin II and a facilitation of the conversion of angiotensin III in angiotensin IV. Thus, the changes in several RAS-regulating specific activities and other enzyme activities involved in the neuroendocrine modulation of gonad and stress-related functions are related to essential hypertension with minor gender differences. Therefore, aminopeptidases constitute new elements for the knowledge of the causes of essential hypertension and an alternative as therapeutic targets against the illness.
...
PMID:Circulating aminopeptidase activities in men and women with essential hypertension. 2393 Dec 76

Receiving help can be a "mixed blessing." Despite the many psychosocial benefits it can carry, it sometimes has negative psychological consequences, such as loss in self-esteem or enhanced guilt. It is, therefore, important to understand the factors that modify responses to receiving help from others. We explored the role of the hormone oxytocin (OT) on affective and social responses to receiving help, given the putative role of OT in social bonding and attunement. To this end, we manipulated whether help was received from a same-sex interaction partner (confederate) versus a control condition, crossed with a double-blind administration of intranasal OT (vs. placebo), and examined subjective and observer-rated participant responses to help. We observed significant interactions between OT and the help manipulation. In the placebo condition, receiving help from the interaction partner compared with the control condition had negative consequences, such that participants reported greater negative affect and came to view themselves and their interaction partners more negatively after interacting together on several tasks. What is important, however, is that OT administration buffered against these negative subjective responses to receiving help. Further, outside observers rated participants who received OT administration as expressing greater happiness and gratitude in response to help, relative to those who received placebo. In sum, in the context of receiving help from a stranger, oxytocin administration fostered more positive affective and social responses. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
 ...
PMID:Effects of oxytocin administration on receiving help. 2917 21

Multiple studies have linked oxytocin to social behavior and affiliation-attachment. This research would suggest that oxytocin function may relate to the absence of loving kindness and empathy in psychopathy. The current study examined the associations between 3 oxytocin-related single-nucleotide polymorphisms (SNPs), participant-reported invalidating childhood environment, and psychopathic traits in community adults, predicting that alleles associated with higher empathy in the literature would relate to lower levels of psychopathic affective traits in particular. Results showed that the rs53576 SNP on the oxytocin receptor and cumulative risk alleles across the 3 SNPs were associated with psychopathic traits, and the interaction between cumulative risk and an emotionally invalidating environment was associated especially with affective deficits of psychopathy. Although this study requires replication in larger samples, results lend support to the role of attachment-related processes in psychopathy. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
 ...
PMID:Oxytocin-related single-nucleotide polymorphisms, family environment, and psychopathic traits. 2992 93

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly prevalent and commonly co-occur. The dual diagnosis of PTSD/AUD is associated with serious negative sequalae, and there are currently no effective pharmacological treatments for this comorbidity. Both PTSD and AUD are characterized by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which helps modulate stress reactivity. Oxytocin, a neuropeptide that attenuates HPA axis dysregulation, may be beneficial for individuals with co-occurring PTSD/AUD. Thus, the current study examined the effects of intranasal oxytocin (40 IU) as compared with placebo on stress reactivity (e.g., cortisol) as well as subjective alcohol craving in response to a laboratory stress task (Trier Social Stress Task). Participants were 67 male U.S. military veterans with current PTSD and AUD (oxytocin n = 32, placebo n = 35; overall mean age = 49.06 years). Baseline cortisol levels were examined as a moderator of outcome. The findings revealed that oxytocin marginally attenuated cortisol reactivity in response to the stress task. Furthermore, oxytocin's effect was moderated by baseline cortisol level, such that oxytocin mitigated cortisol reactivity to a greater extent among participants with higher, as compared with lower, baseline cortisol. Oxytocin did not reduce craving. Although preliminary, the findings are the first to examine oxytocin in co-occurring PTSD/AUD. The findings from this study contribute to the growing literature examining the potential utility of oxytocin among individuals with psychiatric disorders, such as PTSD and substance use disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
 ...
PMID:Effects of oxytocin on stress reactivity and craving in veterans with co-occurring PTSD and alcohol use disorder. 3038 28


1 2 Next >>