Calcium Antagonists and Hormone Release

1984 ◽  
Vol 66 (3) ◽  
pp. 249-255 ◽  
Author(s):  
J. A. Millar ◽  
A. D. Struthers
Keyword(s):  
Calcium Antagonists ◽  
Inhibitory Effect ◽  
Calcium Flux ◽  
Channel Blockers ◽  
Hormone Release ◽  
Calcium Dependent ◽  
Transmembrane Flux ◽  
Slow Channel

Introduction: Calcium (Ca2+) has been aptly entitled the ‘universal provocateur’ [1] in recognition of its many indispensable metabolic actions. The class of drugs popularly known as calcium antagonists (calcium slow channel blockers) provokes a variety of pharmacological effects and these drugs are useful as probes of calcium-dependent mechanisms. One area where such application appears particularly appropriate is the study of hormone release, since it has been demonstrated that secretion of at least some hormones is dependent on translocation of extracellular Ca2+ across the cell membrane. Furthermore, specific physiological stimuli to secretion of most hormones can be applied in vivo or mimicked in vitro, and hormone levels may be measured by specific assays. Calcium antagonists also provide a possible means of studying the role of Ca2+ in hormone release in the intact organism. In many studies an inhibitory effect of a calcium antagonist on hormonal responses to secretory stimuli has been taken as evidence that transmembrane flux of Ca2+ is an obligatory event in the response. Such a conclusion begs several questions, which will be discussed in this review. For example, it is important to define the extent to which calcium antagonists represent a homogeneous class of drugs, whether ‘antagonism’ is restricted to inhibition of inward calcium flux, and whether the pharmacological actions vary according to the agent used or the cell type under study. Answers to such questions are necessary to exclude actions of calcium antagonists other than prevention of calcium uptake which may inhibit hormone release.

On the Release of the Three Locust (Locusta migratoria) Adipokinetic Hormones: Effect of Crustacean Cardioactive Peptide and Inhibition by Sugars

1999 ◽  
Vol 54 (1-2) ◽  
pp. 110-118 ◽  
Author(s):  
James E. Flanigan ◽  
Gerd Gäde
Keyword(s):  
Biological Effects ◽  
Locusta Migratoria ◽  
Inhibitory Effect ◽  
Test System ◽  
Hormone Release ◽  
Adipokinetic Hormone ◽  
High Potassium ◽  
Crustacean Cardioactive Peptide

An existing test to monitor the rate of adipokinetic hormone release from the corpora cardiaca (C C) of Locusta migratoria in vitro was improved, so that a constant basal rate of release was achieved and the amount of released Lom-AKH-I, II and III could be quantified by HPLC . This test system was subsequently used to demonstrate that a small peptide, which has been found in a few insect species including L. migratoria, crustacean cardioactive peptide (CCAP), induces release of all three AKHs. Moreover, 80 mᴍ trehalose reduces CCAP-induced release of AKHs in vitro, and 160 mᴍ glucose reduces this release even further. Glucose also had a greater inhibitory effect than trehalose on the spontaneous release and inhibited the high potassium-stimulated release of AKH from the CC in vitro. Eighty mᴍ sucrose, on the other hand, had no effect on the release of AKH . The effect of trehalose and glucose could be due to their use as an energy source, with trehalose first having to be converted to glucose. Whatever the stimulus, the three AKHs are released in the same proportions as they are found in the CC, which in vivo would make Lom-AKH-I, the most abundant AKH, the major effector of the biological effects of AKHs in adult locusts

An In Vitro Method for Screening Compounds for the Effect on the Rate of Sickling of Erythrocytes

1976 ◽  
Vol 4 (6) ◽  
pp. 375-381 ◽  
Author(s):  
R D Mackenzie ◽  
E M Gleason ◽  
G L Schatzman ◽  
M J Cawein
Keyword(s):  
Whole Blood ◽  
Calcium Concentration ◽  
In Vitro Model ◽  
Inhibitory Effect ◽  
Calcium Flux ◽  
In Vitro System ◽  
Oxygen Dissociation ◽  
Vitro Model

Since no practical animal model is available for the evaluation of compounds in vivo, we have developed an in vitro model for determining the effect of compounds on the rate of sickling of erythrocytes in whole blood taken from patients with sickle cell anaemia. RMI 6792 (a phenethanol-diamine derivative), procaine, and L-glutamine were tested in this in vitro system. RMI 6792 was tested at various concentrations in whole blood. The data indicate that RMI 6792 decreased the rate of sickling at and above 60 μg/ml. Procaine slightly decreased sickling rate at 100 μg/ml. L-glutamine at 555 μg/ml had no inhibitory effect. RMI 6792 and procaine had no effect on the oxygen dissociation curve. RMI 6792 affected the calcium flux of the erythrocytes and the calcium concentration in the erythrocytes.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ying Liu ◽  
Wenjie Liu ◽  
Ziqiang Yu ◽  
Yan Zhang ◽  
Yinghua Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoporosis Treatment ◽  
Inhibitory Effect ◽  
Specific Gene ◽  
Actin Ring ◽  
Treatment Target ◽  
Significant Inhibitory Effect ◽  
Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

scholarly journals Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hayato Mizuta ◽  
Koutaroh Okada ◽  
Mitsugu Araki ◽  
Jun Adachi ◽  
Ai Takemoto ◽  
...  
Keyword(s):  
Gene Rearrangement ◽  
Kinase Inhibitors ◽  
Inhibitory Effect ◽  
In Vivo Model ◽  
Resistance Mutations ◽  
Lung Cancer Patients ◽  
Short Period ◽  
Tki Resistance

AbstractALK gene rearrangement was observed in 3%–5% of non-small cell lung cancer patients, and multiple ALK-tyrosine kinase inhibitors (TKIs) have been sequentially used. Multiple ALK-TKI resistance mutations have been identified from the patients, and several compound mutations, such as I1171N + F1174I or I1171N + L1198H are resistant to all the approved ALK-TKIs. In this study, we found that gilteritinib has an inhibitory effect on ALK-TKI–resistant single mutants and I1171N compound mutants in vitro and in vivo. Surprisingly, EML4-ALK I1171N + F1174I compound mutant-expressing tumors were not completely shrunk but regrew within a short period of time after alectinib or lorlatinib treatment. However, the relapsed tumor was markedly shrunk after switching to the gilteritinib in vivo model. In addition, gilteritinib was effective against NTRK-rearranged cancers including entrectinib-resistant NTRK1 G667C-mutant and ROS1 fusion-positive cancer.

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