Modulatory role of a constitutively active population of α1D-adrenoceptors in conductance arteries

2002 ◽  
Vol 282 (2) ◽  
pp. H475-H481 ◽  
Author(s):  
Khalid Ziani ◽  
Regina Gisbert ◽  
Maria Antonia Noguera ◽  
Maria Dolores Ivorra ◽  
Pilar D'Ocon
Keyword(s):  
Mesenteric Artery ◽  
Functional Role ◽  
Mesenteric Arteries ◽  
The Other ◽  
Active Population ◽  
Abrupt Changes ◽  
Resting Tone ◽  
Constitutively Active

A constitutively active population of α1D-adrenoceptors in iliac and proximal, distal, and small mesenteric rat arteries was studied. The increase in resting tone (IRT) that evidences it was observed only in iliac and proximal mesenteric and was inhibited by prazosin (pIC50 = 9.57), 5-methylurapidil (pIC50 = 7.61), and BMY 7378 (pIC50 = 8.77). Chloroethylchlonidine (100 μmol/l) did not affect IRT, but when added before the other antagonists it blocked their effect. The potency shown by BMY 7378 confirms the α1D-subtype as responsible for IRT. BMY 7378 displayed greater inhibition of adrenergic responses in iliac (pIC50 = 7.57 ± 0.11) and proximal mesenteric arteries (pIC50 = 8.05 ± 0.2) than in distal (pIC50 = 6.94 ± 0.13) or small mesenteric arteries (pIC50 = 6.30 ± 0.14), which confirms the functional role of the α1D-adrenoceptor in iliac and proximal mesenteric arteries. This subtype prevents abrupt changes in iliac and proximal mesenteric artery caliber when the agonist disappears, and this modulatory role is evidenced by the slower decay in the response to norepinephrine after removal.

scholarly journals Pathological role of a constitutively active population of α1D -adrenoceptors in arteries of spontaneously hypertensive rats

2002 ◽  
Vol 135 (1) ◽  
pp. 206-216 ◽  
Author(s):  
Regina Gisbert ◽  
Khalid Ziani ◽  
Raquel Miquel ◽  
M Antonia Noguera ◽  
M Dolores Ivorra ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Active Population ◽  
Constitutively Active

Role of AVP in maintenance of circulatory homeostasis during hemorrhagic shock

1984 ◽  
Vol 246 (2) ◽  
pp. H174-H179 ◽  
Author(s):  
C. E. Hock ◽  
J. Y. Su ◽  
A. M. Lefer
Keyword(s):  
Hemorrhagic Shock ◽  
Cathepsin D ◽  
Mesenteric Artery ◽  
The Other ◽  
Arterial Blood ◽  
Neurohypophyseal Hormone ◽  
Specific Antagonist ◽  
Plasma Arginine ◽  
Artery Flow

Hemorrhagic hypotension produces significantly increased plasma arginine vasopression (AVP) concentrations. We have utilized a specific antagonist (AVP-A) of the pressor effects of endogenous AVP to investigate the role of this neurohypophyseal hormone on the pathogenesis of hemorrhagic shock. Infusion of the AVP-A (2 micrograms/kg bolus + 2 micrograms X kg-1 X h-1 infusion) into sham-shocked animals produced no significant changes in any of the observed experimental variables. Cats subjected to hemorrhagic shock given AVP-A had final superior mesenteric artery flow (SMAF) values significantly (P less than 0.05) higher than shock cats given vehicle (7.7 +/- 1.1 vs. 4.5 +/- 0.8 ml X kg-1 X min-1, respectively). Increases in postreinfusion plasma cathepsin D activities were significantly blunted in hemorrhaged animals treated with AVP-A (10.4 +/- 2.0 vs. 24.8 +/- 5.5 U/mg protein; P less than 0.05). Plasma proteolysis as well as the plasma accumulation of myocardial depressant factor (MDF) were also significantly modulated by AVP-A treatment in hemorrhaged animals. MDF activities were 75 +/- 6 and 53 +/- 4 U/ml (P less than 0.02) for shock cats given vehicle or AVP-A, respectively. However, these beneficial actions were not reflected in any significant improvement in postreinfusion mean arterial blood pressure (MABP). These findings suggest that endogenous AVP functions not only as a potent splanchnic vasoconstrictor but also as a key humoral factor in the maintenance of postreinfusion MABP, a profile that is different from the role of angiotensin II, the other major splanchnic vasoconstrictor, in shock.

Correlation between mRNA levels and functional role of α1-adrenoceptor subtypes in arteries: evidence of α1L as a functional isoform of the α1A-adrenoceptor

2005 ◽  
Vol 289 (5) ◽  
pp. H1923-H1932 ◽  
Author(s):  
Daniel Martí ◽  
Raquel Miquel ◽  
Khalid Ziani ◽  
Regina Gisbert ◽  
M. Dolores Ivorra ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
Mesenteric Arteries ◽  
Main Role ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Response Curves ◽  
Inhibitory Potency ◽  
Adrenoceptor Antagonist ◽  
Relevant Role

The mRNA levels for the three α1-adrenoceptor subtypes, α1A, α1B, and α1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The α1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.7%), α1A predominated in tail (61.7%) and small mesenteric artery (73.3%), and both α1A- and α1D-subtypes were expressed at similar levels in iliac artery. The mRNA levels of the α1B-subtype were a minority in all vessels (1.7–11.1%). Concentration-response curves of contraction in response to phenylephrine or relaxation in response to α1-adrenoceptor antagonists on maximal sustained contraction induced by phenylephrine were constructed from control vessels and vessels pretreated with 100 μmol/l chloroethylclonidine (CEC) for 30 min. The significant decrease in the phenylephrine potency observed after CEC treatment together with the inhibitory potency displayed by 8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-8-azaspiro ( 4 , 5 ) decane-7-dionedihydrochloride} (BMY-7378, an α1D-adrenoceptor antagonist) confirm the relevant role of α1D-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The potency of 5-methylurapidil (an α1A-adrenoceptor antagonist) and the changes in the potency of both BMY-7378 and 5-methylurapidil after CEC treatment provided evidence of a mixed population of α1A- and α1D-adrenoceptors in iliac and distal mesenteric arteries. The low potency of prazosin (pIC50 < 9) as well as the high 5-methylurapidil potency in tail and small mesenteric arteries suggest the main role of α1A/α1L-adrenoceptors with minor participation of the α1D-subtype. The mRNA levels and CEC treatment corroborated this pattern and confirmed that the α1L-adrenoceptor could be a functional isoform of the α1A-subtype.

scholarly journals SUMOylome Modulates Intraflagellar Transport Machinery and Eukaryotic Cilia Motility

2021 ◽  
Author(s):  
Komal Sharma ◽  
Irina Sizova ◽  
Girdhar Pandey ◽  
Peter Hegemann ◽  
Suneel Kateriya
Keyword(s):  
Functional Role ◽  
Intraflagellar Transport ◽  
Small Gtpase ◽  
The Other ◽  
Signaling Proteins ◽  
Sumoylation Site ◽  
C Terminus ◽  
First Time ◽  
Insight Into

Abstract Translocation of channelrhodopsins (ChRs) is mediated by intraflagellar transport (IFT) machinery. However, the functional role of the network containing photoreceptors, IFT and other proteins in controlling cilia motility of the alga is still not fully delineated. In the current study, we identified two important motifs at the C-terminus of ChR1. One of them is similar to a known ciliary targeting sequence that specifically interacts with a small GTPase, and the other is a SUMOylation site. For the first time, experimental data provide an insight into the role of SUMOylation in the modulation of IFT & ChR1. Blocking of SUMOylation affected the phototaxis of C. reinhardtii cells. This implies SUMOylation based regulation of protein network controlling photomotility. The conservation of SUMOylation site pattern as analyzed for the relevant photoreceptors, IFT and its associated signaling proteins in other ciliated green algae suggested SUMOylation based photobehavioural response across the microbes. This report establishes a link between evolutionary conserved SUMOylation and ciliary machinery for the maintenance and functioning of cilia across the eukaryotes. Our enriched SUMOylome of C. reinhardtii comprehends the proteins related to ciliary development and, photo-signaling, along with homologue(s) associated to human ciliopathies as SUMO targets.

Abstract 569: Constitutively Active Notch4 Receptor Promotes Flow-induced Arterial Outward Remodeling

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Lawrence Huang ◽  
Weiya Jiang ◽  
Patrick A Murphy ◽  
Rong A Wang
Keyword(s):  
Shear Stress ◽  
Carotid Artery ◽  
Mesenteric Artery ◽  
High Flow ◽  
Mesenteric Arteries ◽  
Arterial Remodeling ◽  
And Control ◽  
Elastic Lamina ◽  
Medial Area ◽  
Constitutively Active

Notch is expressed in arterial but not venous endothelial cells (ECs). Notch signaling plays a critical role during vascular development and is required for postnatal arterial remodeling following ischemic injury. However, whether activated Notch is sufficient to promote arterial remodeling is unclear. Shear stress is a primary stimulus for arterial outward remodeling, and shear stress induces Notch activation. We hypothesized that activated Notch in turn promotes flow-induced arterial outward remodeling. Constitutively active Notch4 (Notch4*) was expressed in arterial ECs of the carotid artery to bypass hemodynamic perturbations caused by pan-endothelial Notch4 activation. First, we used an artery graft model: a segment of the carotid from a Notch4* donor was grafted into a control recipient. Notch4* expression was restricted to ECs of the graft; hemodynamics in the control recipient was not perturbed. Second, we targeted Notch4* expression using the arterial EC-specific Bmx(PAC)-CreER T2 . The carotid ligation model was used to examine flow-induced outward remodeling. Histological analysis showed that in high-flow Notch4* artery grafts, external elastic lamina (EEL) circumference, EEL area, medial area, and medial thickness were larger compared to controls. In high-flow Bmx-Notch4* arteries, internal elastic lamina circumference, EEL circumference, EEL area, and medial area were larger compared to controls. To bolster our findings in the carotid, we tested our hypothesis using a mesenteric artery ligation model. Post-ligation, shear stress in high-flow Notch4* and control mesenteric arteries were comparable. While high-flow arteries in both Notch4* mutants and controls were enlarged, radial enlargement was increased in Notch4* arteries compared with controls. Together, our results showed that endothelial expression of Notch4* enhanced flow-induced outward remodeling of both the large-diameter, elastic carotid artery and the small-diameter, muscular mesenteric artery. Notably, in the absence of increased flow, basal arterial diameters were comparable between Notch4* and control mice. These data suggest that, when properly targeted to the arterial endothelium, Notch4* promotes flow-induced outward remodeling.

scholarly journals The hidden links between animal weapons, fighting style and their expression on contest resolution

2020 ◽  
Author(s):  
Alexandre V. Palaoro ◽  
Paulo E. C. Peixoto
Keyword(s):  
Body Size ◽  
Functional Role ◽  
Meta Analysis ◽  
The Other ◽  
List Type ◽  
Relative Importance ◽  
Animal Kingdom ◽  
Internal Morphology ◽  
Contest Outcome

SUMMARYIn many species that fight over resources, individuals use specialized structures to overpower their rivals (i.e. weapons). Despite their similar roles for contest settlement (i.e. affecting the winning chances), weapons are highly diverse morphological structures across species. However, the comprehension on how this diversity evolved is still open for debate.Unfortunately, most studies on how weapons are used during contests focus on size asymmetries between winners and losers. Although such information is important to understand, it does not provide much information regarding the mechanisms promoting weapon diversification. In addition, in many situations, the effect of weapon size on contest resolution may be confounded with the effect of body size due to allometric correlations.One way to decompose the relative importance of weapon and body size on contest outcome is to focus on the functional role of weapons. That is, investigate the function of the weapon during contests, and how size should affect its function.We propose two hypotheses that explicitly associate how weapon function may determine the relative importance of weapon and body size in affecting rivals during contests. One based on the internal morphology of the weapon – whether muscles are within the weapon or not – and the other based on fighting style – whether the weapon is used to injure the rival or not.To test our hypotheses, we developed a meta-analysis spanning 31 genera across the animal kingdom.We found that internal morphology and fighting style are important to determine the relative importance of weapon and body size on contest resolution. Weapons that do not have muscles within them (e.g., horns) affect more the chance of winning than weapons that have muscles within them (e.g., claws). Similarly, weapons used to throw/push rivals away (e.g., oversized mandibles) affect more the chance of winning than those used to make the rival flee (e.g., jaws).Overall, we have shown that weapon usage (i.e. weapon function) may affect weapon evolution in predictable ways: weapons without muscles and using for pushing may be selected for size, while muscled weapons used for injuring may be selected for strength.

Redox equilibria of manganese peroxidase from Phanerochaetes chrysosporium: functional role of residues on the proximal side of the haem pocket

2000 ◽  
Vol 349 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Roberto SANTUCCI ◽  
Cristiana BONGIOVANNI ◽  
Stefano MARINI ◽  
Rebecca DEL CONTE ◽  
Ming TIEN ◽  
...  
Keyword(s):  
Manganese Peroxidase ◽  
Functional Role ◽  
Redox Properties ◽  
The Other ◽  
Redox Potentials ◽  
Protonation State ◽  
Alkaline Transition ◽  
Close Proximity ◽  
Redox Equilibria

Redox potentials of recombinant manganese peroxidase from Phanerochaetes chrysosporium have been measured by cyclic voltammetry as a function of pH, between pH 4.5 and pH 10.5. They display a bimodal behaviour (characterized by an ‘alkaline’ and an ‘acid’ transition), which indicates that (at least) two protonating groups change their pKb values upon reduction (and/or oxidation) of the iron atom in haem. Analogous measurements have been carried out on four site-directed mutants involving residues in close proximity to the proximal ligand, His173, in order to investigate the role played by residues of the proximal haem pocket on the redox properties of this enzyme. Results obtained suggest that the protonation state of N∆ of the proximal imidazole group is redox-linked and that it is crucial in regulating the ‘alkaline’ transition. On the other hand, none of the proximal mutants alters the ‘acid’ transition, suggesting that it is modulated by groups located in a different portion of the protein.

Bridging the gap between the other and me: the functional role of motor resonance and action effects in infants’ imitation

2011 ◽  
Vol 14 (4) ◽  
pp. 901-910 ◽  
Author(s):  
Markus Paulus ◽  
Sabine Hunnius ◽  
Marlies Vissers ◽  
Harold Bekkering
Keyword(s):  
Functional Role ◽  
The Other ◽  
Motor Resonance ◽  
Action Effects

scholarly journals The vasodilatory mechanism of nitric oxide and hydrogen sulfide in human mesenteric artery of colorectal cancer patients: role of potassium channels

2019 ◽  
Author(s):  
Awat Y. Hassan ◽  
Ismail M. Maulood ◽  
Abbas Salihi
Keyword(s):  
Cancer Progression ◽  
Mesenteric Artery ◽  
Serum Levels ◽  
Mesenteric Arteries ◽  
Relaxation Rates ◽  
Time Intervals ◽  
Vasodilator Activity ◽  
Colorectal Cancer Patients ◽  
And Oxidative Stress

AbstractRecent studies focused on the role of gasotransmitters in cancer progression and prevention. Therefore, this study was designed to explore the vasodilator activity of NO and H2S in human mesenteric artery of CRC patients via activation of K+ channels. For this purpose, two sets of experiments were established. The blood samples from CRC patients were obtained to detect serum levels of Endocan and MDA. Moreover, the role of K+ channels were assessed in mediating vasodilation of human mesenteric artery in response to SNP and Na2S. The level of serum Endocan was decreased in CRC patients compared to healthy individuals, while serum MDA was not changed. The arterial rings precontracted with NE were first relaxed by cumulative addition of increasing concentrations of either SNP (30nM-30μM) or Na2S (1-6mM). Then maximal relaxation rates were calculated for four times at each 15min intervals. Preincubation of arterial rings for 20min with individual K+ channels blockers were significantly reduced relaxation caused by SNP and Na2S at different time intervals. Furthermore, pretreatment of L-NAME did not change the vasodilation induced by Na2S. Vasodilation of CRC mesenteric unchanged by synergistic application of SNP and Na2S. While preincubation of arterial rings with PAG significantly enhanced vasodilation induced by SNP. In conclusion, these results indicate that endothelial dysfunction and oxidative stress do not take part in the pathogenesis of CRC. The dilatory mechanisms of NO and H2S in mesenteric arteries of CRC patients are K+ channels and time dependent, and the activity of CSE enzyme slows down the vasodilator ability of exogenous NO.

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