scholarly journals Role of estrogen receptor subtypes in estrogen-induced organ-specific vasorelaxation after trauma-hemorrhage

2008 ◽  
Vol 295 (5) ◽  
pp. H2061-H2067 ◽  
Author(s):  
Zheng F. Ba ◽  
Irshad H. Chaudry
Keyword(s):  
Estrogen Receptor ◽  
Small Intestine ◽  
Receptor Subtypes ◽  
Circulating Blood Volume ◽  
Heart Performance ◽  
Organ Specific ◽  
Isolated Perfusion ◽  
Specific Organ ◽  
T Values

Although endothelin-1 (ET-1)-induced organ hypoperfusion after trauma-hemorrhage is improved by estrogen administration, it remains unclear whether estrogen receptor (ER) subtypes play any role in the attenuation of ET-1-induced vasoconstriction in any specific organ bed. To investigate this, isolated perfusion experiments in the heart, liver, small intestine, kidney, and lung were carried out in sham, at the time of maximum bleedout (MBO; i.e., 5-cm midline incision, with removal of 60% of circulating blood volume over 45 min to maintain a mean blood pressure of 40 mmHg), and 2 h after trauma-hemorrhage and resuscitation (T-H/R). Organ-specific ET-1-induced vasoconstriction was evaluated, and the effects of 17β-estradiol (E2) and ER-specific agonists propylpyrazole triol (PPT; ERα agonist) and diarylpropionitrile (DPN; ERβ agonist) were determined. ET-1 induced the greatest vasoconstriction in sham animals, with the strongest response in the kidneys, followed by the small intestine and liver. ET-1-induced responses were weakest in the heart and lungs. ET-1-induced vasoconstriction was evident at the time of MBO but was significantly decreased at 2 h after T-H/R. ERβ plays an important role in cardiac performance, as evidenced by improved heart performance (+dP/d t) in the presence of DPN. DPN also induced a greater effect than PPT in the reduction of ET-1-induced vasoconstriction in the kidneys and lungs. In contrast, PPT attenuated ET-1-induced vasoconstriction in the liver, whereas both DPN and PPT were equally effective in the small intestine. The increased +dP/d t values induced by E2, DPN, or PPT were evident at the time of MBO but were significantly decreased at 2 h after T-H/R. These data indicate that the effects of ET-1 on vasoconstriction and the role of ER subtypes in estrogen-induced vasorelaxation are organ specific and temporally specific after trauma-hemorrhage.

Estrogen Neuroprotection and Anti-Inflammation Actions in the Hippocampus

2020 ◽  
pp. 401-415
Author(s):  
Roshni D. Thakkar ◽  
Ruimin Wang ◽  
Gangadhara R. Sareddy ◽  
Ratna K. Vadlamudi ◽  
Darrell W. Brann
Keyword(s):  
Traumatic Brain Injury ◽  
Estrogen Receptor ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Glutamic Acid ◽  
Steroid Hormone ◽  
Receptor Subtypes ◽  
Activator Protein ◽  
Anti Inflammation

The steroid hormone 17β‎-estradiol (E2) is neuroprotective in several neurodegenerative conditions, including cerebral ischemia, traumatic brain injury, and Alzheimer’s disease (AD). This chapter focuses on the evidence supporting a neuroprotective role of E2 in the hippocampus in cerebral ischemia and AD and reviews various mechanisms thought to underlie E2-induced neuroprotection. Specifically, the chapter discusses the mechanistic role of (a) the various estrogen receptor subtypes, (b) genomic versus nongenomic signaling, (c) regulation of the prosurvival Wnt/β‎−catenin pathway, and (d) anti-inflammatory effects of E2 in the hippocampus. Finally, we also discuss the role of a novel estrogen receptor co-activator protein, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) in mediating E2 genomic and non-genomic signaling, as well as the neuroprotective and cognitive-enhancing effects of E2 in the hippocampus.

The role of estrogen receptor subtypes for vascular maintenance

2009 ◽  
Vol 25 (2) ◽  
pp. 82-95 ◽  
Author(s):  
Leanid Luksha ◽  
Karolina Kublickiene
Keyword(s):  
Estrogen Receptor ◽  
Receptor Subtypes

Combinatorial anti-proliferative effects of tamoxifen and naringenin: The role of four estrogen receptor subtypes

Toxicology ◽  
2018 ◽  
Vol 410 ◽  
pp. 231-246 ◽  
Author(s):  
Zhixiang Xu ◽  
Bin Huang ◽  
Jun Liu ◽  
Xinhao Wu ◽  
Nao Luo ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Receptor Subtypes

5-HT-induced jejunal motor activity: enteric locus of action and receptor subtypes

1996 ◽  
Vol 270 (6) ◽  
pp. G992-G1000 ◽  
Author(s):  
S. Graf ◽  
S. K. Sarna
Keyword(s):  
Small Intestine ◽  
Cholinergic Neurons ◽  
Conscious State ◽  
Inhibitory Neurons ◽  
Phase Iii ◽  
Receptor Subtypes ◽  
Receptor Antagonists ◽  
Spontaneous Phase ◽  
Giant Migrating Contractions

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and receptor subtypes involved in the regulation of jejunal contractions were investigated by close intra-arterial infusions in conscious dogs. Close intra-arterial infusions of 5-HT in short segments of the jejunum stimulated phasic contractions that were blocked completely by atropine, partially by tetrodotoxin, and not affected by hexamethonium. This response was also blocked significantly by 5-HT2A and 5-HT2C receptor antagonists but was not affected by 5-HT1A/5-HT1B, 5-HT3, and 5-HT4 receptor antagonists. Spontaneous phase III contractions were inhibited significantly by 5-HT2A and 5-HT2C receptor antagonists, not affected by 5-HT1A/5-HT1B and 5-HT3 receptor antagonists, and enhanced by 5-HT4 receptor antagonists. Repeated close intra-arterial infusions of 5-HT over several days stimulated giant migrating contractions. We conclude that in the conscious state, 5-HT acts on 5-HT2A and 5-HT2C receptors located on postsynaptic cholinergic neurons in the canine jejunum to stimulate phasic contractions and phase III activity. The 5-HT4 receptors in the canine small intestine may be localized on nonadrenergic, noncholinergic inhibitory neurons; these receptors suppress the amplitude and duration of phase III activity.

The role of estrogen receptor subtypes for induction of delayed effects on the estrous cycle and female reproductive organs in rats

2017 ◽  
Vol 17 (1) ◽  
pp. 111-119
Author(s):  
Miwa Takahashi ◽  
Ryohei Ichimura ◽  
Kaoru Inoue ◽  
Tomomi Morikawa ◽  
Kazunori Kuwata ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrous Cycle ◽  
Reproductive Organs ◽  
Receptor Subtypes ◽  
Delayed Effects ◽  
Female Reproductive Organs

Role of 5-HT in cholera toxin-induced mucin secretion in the rat small intestine

1996 ◽  
Vol 270 (6) ◽  
pp. G1001-G1009 ◽  
Author(s):  
B. A. Moore ◽  
K. A. Sharkey ◽  
M. Mantle
Keyword(s):  
Small Intestine ◽  
Receptor Antagonist ◽  
Cholera Toxin ◽  
Receptor Subtypes ◽  
Rat Small Intestine ◽  
Mucin Secretion ◽  
Common Pathway ◽  
Distal Small Intestine ◽  
Intestinal Segments

We examined the role of 5-hydroxytryptamine (5-HT) in cholera toxin (CT)-induced mucin secretion in the proximal and distal regions of the rat small intestine. Neither the 5-HT2 receptor antagonist ketanserin nor the cyclooxygenase inhibitor indomethacin was capable of inhibiting choleraic mucin secretion. However, in the presence of the mixed 5-HT3/4 receptor antagonist tropisetron at doses that block both receptor subtypes, the secretory response was reduced to baseline levels in the proximal and distal small intestine. The selective 5-HT3 receptor antagonist ondansetron had no significant effect. These findings suggest that choleraic mucin secretion is mediated primarily through the activation of a 5-HT4-like receptor. Mucin secretion in response to the exogenous application of 5-HT occurs via two pathways: one is mediated by a 5-HT4-like receptor and is capsaicin sensitive but tetrodotoxin (TTX) insensitive, and one lacks the capsaicin-sensitive 5-HT4-mediated response but is TTX sensitive. Both converge on a common pathway that is cholinergic. No significant differences were observed between proximal and distal intestinal segments.

scholarly journals Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa

2004 ◽  
Vol 286 (3) ◽  
pp. G458-G466 ◽  
Author(s):  
Naoki Hosoe ◽  
Soichiro Miura ◽  
Chikako Watanabe ◽  
Yoshikazu Tsuzuki ◽  
Ryota Hokari ◽  
...  
Keyword(s):  
Small Intestine ◽  
T Lymphocyte ◽  
Intestinal Mucosa ◽  
Intravital Microscopy ◽  
Functional Role ◽  
Intraepithelial Lymphocytes ◽  
Tnf Α ◽  
Organ Specific

It has recently been suggested that C-C chemokines may play a role in the organ-specific homing of lymphocytes, but there is not enough in vivo evidence in intestinal mucosa. The aim of this study was to examine whether thymus-expressed chemokine (TECK)/CCL25 and its ligand CCR9 are involved in T-lymphocyte interaction with microvessels of murine intestinal mucosa. T lymphocytes from the small intestine were fluorescence labeled, and their adhesion to mucosal microvessels was observed by intravital microscopy. Lamina proprial lymphocytes (LPL) and intraepithelial lymphocytes (IEL) adhered to both the small intestine and colon, and desensitization of CCR9 with TECK/CCL25 or anti-TECK/CCL25 antibody significantly inhibited these adhesions only in small intestine. At both sites, TNF-α significantly increased LPL adhesion but not IEL adhesion. Desensitization of CCR9 or anti-TECK/CCL25 antibody also attenuated the TNF-α-induced LPL adhesion in the small intestine. Increased expression of TECK/CCL25 by TNF-α was observed in the lamina propria of small intestine. TECK/CCL25 may thus play an important role in the adherence of mucosal lymphocytes to the microvessels of the small intestine but not the colon under uninflamed as well as inflamed conditions.

Impact of Nanotechnology on the Future of Pharmaceuticals and Nutraceuticals: The Road toward Precision Medicines—Case Studies

2021 ◽  
Vol 7 (1) ◽  
pp. 12
Author(s):  
Shaker Mousa
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Innovative Technology ◽  
Specific Cell ◽  
Slide Presentation ◽  
The Road ◽  
Simultaneous Imaging ◽  
Organ Specific ◽  
Specific Organ

Our Work focuses on the development of active molecular targeting utilizing novel conjugated specific targeting molecules that differentially target specific organ or diseased area with minimal distribution into normal organs in order to achieve optimal efficacy and safety profiles. In that regards, over the past decade, evidence from the scientific and medical communities has demonstrated that nanobiotechnology and nanomedicine have tremendous potential to affect numerous aspects of cancer and other disorders in terms of early diagnosis and targeted therapy [1,2,3,4]. The utilization of nanotechnology for the development of new nanocarrier systems has the potential to offer improved targeted delivery through increased solubility and sustained retention and, more importantly, active targeting. One of the major advantages of this innovative technology is its unique multifunctional characteristics [1,2,3,4]. Targeted delivery of drug-incorporated nanoparticles, through the conjugation of site-specific cell surface markers, such as tumor-specific antibodies or ligands, can enhance the efficacy of the anticancer drug and reduce the side effects [3,4,5,6]. Additionally, multifunctional characteristics of the nanocarrier system would allow for simultaneous imaging of tumor mass, targeted drug delivery and monitoring (theranostics). A summary of the recent progress in nanotechnology as it relates to nanoparticles and drug delivery are reviewed in the slide presentation. Nano nutraceuticals, using a combination of various natural products, provide great potential in disease prevention [4]. Additionally, various nanomedicine approaches for the detection and treatment of various types of organ-specific delivery, vascular targeting, and vaccines are highlighted in the slide presentation. In conclusion, this presentation highlighted the key role of nanobiotechnology in achieving effective and safe pharmaceuticals, optimizing vaccine delivery, targeting the delivery for optimal biodistribution into targeted sites as well as improving PK and PD and minimizing impact of pharmacogenomic variables. These aspects could accelerate the transition from nanomedicines into precision medicines.

The role of CXCL12 in the organ-specific process of artery formation

Blood ◽  
2005 ◽  
Vol 105 (8) ◽  
pp. 3155-3161 ◽  
Author(s):  
Toshiaki Ara ◽  
Koji Tokoyoda ◽  
Rika Okamoto ◽  
Pandelakis A. Koni ◽  
Takashi Nagasawa
Keyword(s):  
Endothelial Cells ◽  
Small Intestine ◽  
B Lymphopoiesis ◽  
Capillary Plexus ◽  
Organ Specific ◽  
Chemokine Ligand ◽  
Stromal Cell Derived Factor ◽  
Primary Capillary Plexus ◽  
Arterial Endothelial Cells

AbstractCXC chemokine ligand 12 (CXCL12; stromal cell-derived factor-1 [SDF-1]/pre-B-cell growth-stimulating factor [PBSF]) and its receptor CXCR4 are essential for vascularization in the gastrointestinal tract as well as B lymphopoiesis and colonization of bone marrow by hematopoietic cells. However, the mechanism by which CXCL12/CXCR4 functions in blood vessel formation remains elusive. Here, we have found a novel mode of organ vascularization and determined the roles of CXCL12 in these processes. In the developing small intestine, many short interconnecting vessels form between larger superior mesenteric artery (SMA) and the neighboring primary capillary plexus surrounding the primitive gut, and they elongate and become the arteries supplying the small intestine. Mice lacking CXCL12 or CXCR4 lack the interconnecting vessels but have normal venous networks. The mutants lack filopodial extension and intussusception from endothelial cells of SMAs seen in wild-type embryos. CXCR4 is specifically expressed in arteries in the developing mesenteries and its expression is severely reduced in CXCL12–/– embryos. Mice in which CXCR4 is specifically deleted in the endothelium reveal vascular defects identical to those observed in the conventional CXCR4–/– embryos. Together, CXCL12 acts on arterial endothelial cells of SMA to up-regulate CXCR4 and mediate the connection between the larger artery and neighboring capillary plexus in an organ-specific manner.

scholarly journals Differential Neuroprotection of Selective Estrogen Receptor Agonists against Autonomic Dysfunction and Ischemic Cell Death in Permanent versus Reperfusion Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Barry J. Connell ◽  
Tarek M. Saleh
Keyword(s):  
Cell Death ◽  
Estrogen Receptor ◽  
Reperfusion Injury ◽  
Autonomic Dysfunction ◽  
Ischemia Reperfusion ◽  
Baroreceptor Reflex ◽  
Receptor Subtypes ◽  
Baroreceptor Reflex Sensitivity ◽  
Dose Dependent

In the present study, we tested the hypothesis that selective activation of estrogen receptor subtypes (ERαand ERβ) would be neuroprotective following ischemia and/or ischemia-reperfusion, as well as prevent the associated autonomic dysfunction. The selective ERαagonist, PPT, when administered 30 min prior to occlusion of the middle cerebral artery (pMCAO), resulted in a dose-dependent neuroprotection as measured 6 hours postpermanent MCAO, but not following 30 mins of MCAO followed by 5.5 hrs of reperfusion (I/R). In contrast, 30 min pretreatment with the selective ERβagonist, DPN, resulted in a dose-dependent neuroprotection following I/R, but was not protective following pMCAO. Both drugs prevented the ischemia-induced autonomic dysfunction as measured by a decrease in the baroreceptor reflex sensitivity (BRS). The data presented here suggest a differential role of each ER subtype in targeting the mechanisms of cell death that occur in ischemia versus reperfusion injury.

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