scholarly journals Progesterone induces the release of bull spermatozoa from oviductal epithelial cells

2019 ◽  
Vol 31 (9) ◽  
pp. 1463 ◽  
Author(s):  
J. Romero-Aguirregomezcorta ◽  
S. Cronin ◽  
E. Donnellan ◽  
S. Fair
Keyword(s):  
Epithelial Cells ◽  
Receptor Antagonist ◽  
Mechanism Of Action ◽  
Initial Dose ◽  
Inhibitory Action ◽  
Cumulus Cells ◽  
Optimum Concentration ◽  
Cation Channels ◽  
Bovine Oocyte ◽  
Bovine Spermatozoa

The mechanism that causes the detachment of spermatozoa from the oviductal reservoir around the time of ovulation remains to be elucidated. Because the cumulus cells of the bovine oocyte are known to secrete progesterone (P4), and P4 has been shown to act upon cation channels of spermatozoa (CatSper) in human spermatozoa, it was hypothesised that P4 could induce hyperactivation due to an influx of extracellular calcium, and this would facilitate detachment of spermatozoa from oviductal epithelial cells. Therefore, this study aimed to investigate the role and mechanism of action of P4 in the release of spermatozoa from bovine oviduct epithelial cells (BOEC). Initial dose–response assessments on sperm hyperactivation determined the optimum concentration of P4 (10 nM), mibefradil (a non-specific Ca2+ channel antagonist; 5µM), NNC 55-0396 dihydrochloride (NNC; a CatSper antagonist; 2µM), mifepristone (a classical and membrane P4 receptor antagonist; 400nM) and AG205 (a membrane P4 receptor antagonist; 10μM). BOEC explants were incubated with frozen–thawed bovine spermatozoa for 30min, following which loosely bound spermatozoa were removed. Two experiments were completed. In Experiment 1, BOECs were treated for 30min with either no treatment, P4, NNC, mibefradil, P4+mibefradil, P4+NNC, P4+mibefradil+NNC or P4+EGTA. In Experiment 2, BOECs were treated for 30min with either no treatment, P4, mifepristone, AG205, mifepristone+AG205, P4+mifepristone, P4+AG205 or P4+mifepristone+AG205. The number of spermatozoa remaining bound per millimetre squared of BOEC explant was determined. Progesterone stimulated the release of bound spermatozoa from BOEC explants, whereas NNC, mibefradil and EGTA inhibited this release. The release of spermatozoa by P4 was inhibited in the presence of both mifepristone and AG205, whereas the combination of both had the greatest inhibitory action on P4 release of spermatozoa. These findings suggest the presence of a P4 membrane receptor on bovine spermatozoa and that P4-induced release of spermatozoa from BOECs is likely mediated by extracellular Ca2+.

The Effect of Agonists and Antagonists of Platelet Aggregation on von Willebrand Factor-Mediated Platelet Agglutination

1991 ◽  
Vol 65 (05) ◽  
pp. 573-577 ◽  
Author(s):  
Jean McPherson ◽  
Marjorie B Zucker ◽  
Evelyn A Mauss ◽  
Sandra Brownlea
Keyword(s):  
Receptor Antagonist ◽  
Intracellular Calcium ◽  
Calcium Ions ◽  
Inhibitory Action ◽  
Platelet Rich Plasma ◽  
Cytoskeletal Proteins ◽  
A 23187 ◽  
Sulphydryl Groups ◽  
Affinity Receptor ◽  
Adp Receptor

SummaryRistocetin-induced platelet agglutination (RIPA) in EDTA-treated citrated platelet-rich plasma was reduced to 49 ± 11% by 1.25 ΜM ADP, 41 ± 14% by 1 ΜM A 23187, and 26 ± 7% by 0.1 Μg/ml platelet activating factor (PAF). The effect of 5-110 ΜM epinephrine was not dose-dependent, but varied between donors, with RIPA from 56-100% of the control. The inhibitory effects of these agonists were not altered by prior treatment of platelets with aspirin. Prior addition of 200 ΜM ATP (an ADP receptor antagonist acting at both high and low affinity ADP receptors) prevented the inhibitory action of ADP but not that of A 23187 or PAF, suggesting that the inhibitory actions of the latter are not mediated by released ADP. As 700 ΜM 8-bromoadenosine 5-diphosphate (an ADP receptor antagonist acting mainly at the high affinity receptor) did not prevent ADP-induced inhibition of RIPA, interaction of ADP with the low affinity receptor is presumably responsible for its inhibitory action. As A 23187, but not phorbol myristate acetate (0.1 ΜM) inhibited RIPA, an increase in intracellular calcium ions rather than direct stimulation of protein kinase C appears to mediate agonist-induced inhibition. Cytochalasin B (10.5-21 ΜM), dibucaine (0.5-1 mM), and prostaglandin E1 (25 nM), added before or after the agonist, prevented or reversed ADP-, A23187-, and PAF-induced inhibition of RIPA, suggesting that the state of the platelet cytoskeleton affects inhibition. N-ethylmaleimide (0.25-0.5 mM), an agent that can penetrate cell membranes and block sulphydryl groups, prevented or reversed ADP, A 23187- and PAF-induced inhibition of RIPA, but 0.5 mM dithionitrobisbenzoic acid, a non-penetrating sulphydryl blocker, had no effect. Diamide (0.1-0.5 mM), an agent that can crosslink cytoskeletal proteins by oxidation of sulphydryl groups, reduced RIPA. Thus an increase in intracellular calcium ions with resultant cytoskeletal changes and reorganisation of intracellular sulphydryl groups may mediate the inhibitory action of agonists on RIPA.

Quinoxaline 1,4-di-N-Oxide Derivatives: Are They Unselective or Selective Inhibitors?

2021 ◽  
Vol 21 ◽  
Author(s):  
Gildardo Rivera
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Lines ◽  
Mechanism Of Action ◽  
Inhibitory Action ◽  
Triosephosphate Isomerase ◽  
Trypanothione Reductase ◽  
Selective Inhibitors ◽  
Oxide Ring ◽  
Privileged Structure

Background: For decades, the quinoxaline 1,4-di-N-oxide ring has been considered a privileged structure to develop new antibacterial, antitumoural, and antiprotozoal agents, among others, however its mechanism of action is not clear. Objective : The main aim of this mini-review was to analyze the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives reported as antibacterial, antitumoural and antiprotozoal agents. Results : Initially, the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives against bacteria, tumoural cell lines, and parasites has been described as nonspecific, but recently, the results against different organisms have shown that these compounds have an inhibitory action on specific targets such as trypanothione reductase, triosephosphate isomerase, and other essential enzymes. Conclusion: In summary, quinoxaline 1,4-di-N-oxide is a scaffold to develop new anti-Mycobacterium tuberculosis, antitumoural and antiprotozoal agents, however, understanding the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives in each microorganism could contribute to the development of new, and more potent selective drugs.

Role of vasopressin on cardiovascular changes during hemorrhage in conscious rats

1994 ◽  
Vol 267 (5) ◽  
pp. H1713-H1718 ◽  
Author(s):  
Y. Fujisawa ◽  
A. Miyatake ◽  
Y. Hayashida ◽  
Y. Aki ◽  
S. Kimura ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Inhibitory Action ◽  
Sympathetic Nerve Activity ◽  
Stimulatory Action ◽  
Renal Sympathetic Nerve Activity ◽  
Conscious Rats ◽  
V2 Receptor ◽  
Regulation Of Blood Pressure ◽  
Renal Sympathetic

Hypotensive hemorrhage decreases heart rate (HR) and renal sympathetic nerve activity (RSNA). Hemorrhage is a potent stimulus for arginine vasopressin (AVP) release; therefore, AVP may contribute to such inhibitory action of HR and RSNA during hemorrhage. We evaluated the roles of vasopressin on the regulation of blood pressure (BP), HR, and RSNA during hemorrhage using nonpeptide and selective V1- and V2-receptor antagonists (OPC-21268 and OPC-31260) in conscious rats. After hemorrhage (20 ml/kg body wt) BP decreased by 62 +/- 10 mmHg along with bradycardia (-110 +/- 15 beats/min) and renal sympathoinhibition (-50 +/- 8). Pretreatment of V1-receptor antagonist (5 mg/kg iv) did not affect the initial fall of BP but attenuated subsequent BP recovery. Bradycardic and renal sympathoinhibitory responses following hemorrhage were abolished (-14 +/- 24 beats/min and -7 +/- 9) by V1-receptor antagonist. Pretreatment of V2-receptor antagonist (1 mg/kg iv) did not affect the response of BP; however, it did slightly strengthen bradycardia and prolong renal sympathoinhibition. Hemorrhage increased the plasma AVP concentration more than 50-fold. These results indicate that when the plasma concentration of AVP is extremely high during hemorrhage, vasopressin via V1 receptor contributes to BP recovery by the peripheral vasoconstriction and exerts an inhibitory action on RSNA, and vasopressin via V2 receptor exerts opposite stimulatory action on RSNA.

scholarly journals Effects of Different Maturation Media on In Vitro Produced Bovine Embryos Co-Cultured with Bovine Oviduct Epithelial Cells or Cumulus Cells

1995 ◽  
Vol 12 (1) ◽  
pp. 9-13 ◽  
Author(s):  
C. Larocca ◽  
S. Kmaid ◽  
J. Calvo ◽  
J.E. Romano ◽  
M. Viqueira ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cumulus Cells ◽  
Bovine Embryos ◽  
Oviduct Epithelial Cells

Potential therapy of Sambiloto plant (Andrographis paniculata) using multi-compounds analysis

2021 ◽  
Vol 129 (4) ◽  
Author(s):  
Handayani ◽  
Wiwik Winarningsih
Keyword(s):  
Herbal Medicine ◽  
Receptor Antagonist ◽  
Mechanism Of Action ◽  
Receptor Agonist ◽  
Kinase Inhibitor ◽  
Therapeutic Potential ◽  
Andrographis Paniculata ◽  
Chemical Bonds ◽  
Receptor Kinase ◽  
Active Content

Introduction: Sambiloto plant (Andrographis paniculata) is often used as herbal medicine plant in Indonesia. Previous evidence indicates the use of a whole plant or single-compound approach. Analysis of multi-compounds is needed to determine the therapeutic potential for standardizing herbal medicine to provide a reliable effect. Methods: An exploratory study searching for the active content of A. paniculata was carried out in the Knapsack program. The chemical structure is analyzed computationally using Prediction of Activity Spectra for Substances (PASS) software. The analysis of the mechanism of action of drug molecules was analyzed using the Search Tool for Interacting Chemicals (STITCH) software. Results: The active content of A. paniculata is 46 types, with 5 of them having 6 effects based on chemical bonds and targeting 12 receptor proteins. Five active contents of A. paniculata include andrographidin A, caffeic acid, chlorogenic acid, wogonin 5-glucoside, and cinnamic acid. Analysis of the mechanism of action of A. paniculata based on 12 target proteins from active ingredients using a multi-compound approach shows 6 unique biological processes. Based on the chemical bonds, 5 active contents of A. paniculata have six effects, including anaphylatoxin receptor antagonist, a beta-adrenergic receptor kinase inhibitor, GABA C receptor agonist, G-protein-coupled receptor kinase inhibitor, Aryl hydrocarbon receptor agonist, and Nicotinic alpha6beta3beta4alpha5 receptor antagonist. Conclusion: There is a therapeutic potential of A. paniculata with multi-compounds analysis. A molecular docking analysis is needed to predict the affinity between the ligand (active ingredient) and the target protein.

ATP Receptor-Operated Ca2+ Influx and Catecholamine Release From Neuronal Cells

Physiology ◽  
1992 ◽  
Vol 7 (2) ◽  
pp. 56-59 ◽  
Author(s):  
K Inoue ◽  
K Nakazawa
Keyword(s):  
Mechanism Of Action ◽  
Physiological Function ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Extracellular Atp ◽  
Catecholamine Release ◽  
Cation Channels ◽  
Pc 12 Cells ◽  
P2 Purinoceptors

The physiological function of extracellular ATP was investigated using PC-12 cells as a model neuronal cell. The mechanism of action of ATP proposed is that ATP stimulates P2-purinoceptors, activates Ca2+-permeable cation channels, and causes Ca2+ influx, triggering catecholamine release.

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