Current medicinal chemistry. Cardiovascular and hematological agents最新文献_第9页

Capsaicin sensitive-sensory nerves and blood pressure regulation. 辣椒素敏感感觉神经和血压调节。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477540

Prashant Vaishnava, Donna H Wang

{"title":"Capsaicin sensitive-sensory nerves and blood pressure regulation.","authors":"Prashant Vaishnava, Donna H Wang","doi":"10.2174/1568016033477540","DOIUrl":"https://doi.org/10.2174/1568016033477540","url":null,"abstract":"Capsaicin (8-methyl-N-vannillyl-6-nonenamide), via binding to the vanilloid receptor subtype 1 (VR1), stimulates a subpopulation of primary afferent neurons that project to cardiovascular and renal tissues. These capsaicin-sensitive primary afferent neurons are not only involved in the perception of somatic and visceral pain, but also have a \"sensory-effector\" function. Regarding the latter, these neurons release stored neuropeptides through a calcium-dependent mechanism via the binding of capsaicin to the VR1. A subset of capsaicin-sensitive sensory nerves contains calcitonin gene-related peptide (CGRP) and substance P (SP). These sensory neuropeptides are potent vasodilators and natriuretic/diuretic factors. Neonatal degeneration of capsaicin-sensitive sensory nerves has revealed novel mechanisms that underlie increased salt sensitivity and several experimental models of hypertension. These mechanisms are reviewed, which include insufficient suppression of plasma renin activity and plasma aldosterone levels subsequent to salt loading, enhancement of sympathoexcitatory response in the face of a salt challenge, activation of the endothelin-1 receptor, and impaired natriuretic response to salt loading in capsaicin-pretreated rats. These data indicate that sensory nerves counterbalance the prohypertensive effects of several neuro-hormonal systems to maintain normal blood pressure when challenged with salt loading. Mechanisms underlying pneumotoxicity and pulmonary hypertension as revealed by degeneration of capsaicin-sensitive nerves are also discussed. Finally, the therapeutic utilities of capsaicin, endogenous anandamide, and CGRP agonists are assessed.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 2","pages":"177-88"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016033477540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24644114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 40

Structure-activity relationships of snake toxins targeting platelet receptors, glycoprotein Ib-IX-V and glycoprotein VI. 蛇毒素靶向血小板受体、糖蛋白Ib-IX-V和糖蛋白VI的构效关系。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477559

Robert K Andrews, Elizabeth E Gardiner, Yang Shen, Michael C Berndt

{"title":"Structure-activity relationships of snake toxins targeting platelet receptors, glycoprotein Ib-IX-V and glycoprotein VI.","authors":"Robert K Andrews, Elizabeth E Gardiner, Yang Shen, Michael C Berndt","doi":"10.2174/1568016033477559","DOIUrl":"https://doi.org/10.2174/1568016033477559","url":null,"abstract":"Initiation of thrombus formation involves the platelet adhesion receptors, glycoprotein (GP)Ib-IX-V and GPVI, that bind von Willebrand factor (vWF) and collagen, respectively. These interactions trigger intracellular signals leading to degranulation, elevation of cytosolic Ca2+, cytoskeletal rearrangements, and \"inside-out\" activation of the integrin, GPIIb-IIIa (alphaIIbbeta3) that binds von Willebrand Factor (vWF) or fibrinogen and mediates platelet aggregation. GPIbalpha (the vWF-binding subunit of GPIb-IX-V) of the leucine-rich repeat protein family and GPVI of the immunoglobulin superfamily not only have a parallel physiological function, but recent studies of these receptors have revealed structure-activity relationships amongst snake venom toxins which target them. Two families of venom proteins, the C-type lectin-like proteins and metalloproteinase-disintegrins, target GPIbalpha, GPVI and/or the collagen-binding integrin, GPIa-IIa (alpha2beta1). Members of the C-type lectin family interact specifically with GPIbalpha (echicetin, alboaggregin-B, agglucetin), GPVI (convulxin, ophioluxin) or GPIa-IIa (rhodocetin), whereas related proteins accomplish dual receptor occupancy and bind GPVI and GPIbalpha (alboaggregin-A, alboluxin), or GPIbalpha and GPIa-IIa (aggretin). These latter venom proteins mimic physiological ligands, vWF or collagen, which also recognize more than one receptor. Similarly, metalloproteinase-disintegrin family proteins target GPlbalpha (mocarhagin, crotalin), GPVI (alborhagin) or GPIa-IIa (jararhagin), resulting in inhibition or induction of platelet aggregation by proteolytically dependent or independent mechanisms. Anti-thrombotics based on snake venom GPIIb-IIIa inhibitors have been investigated clinically, however analogous proteins recognizing GPIb-IX-V or GPVI are yet to be therapeutically exploited.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 2","pages":"143-9"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016033477559","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24644111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Bone marrow reconstitution as a relevant model of genetically programmed leukemia. 骨髓重构作为基因程序性白血病的相关模型。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477531

A Dolnikov, S Shen, T Passioura, G Symonds

引用次数: 3

1-Azaadamantanes: pharmacological applications and synthetic approaches. 1-Azaadamantanes:药理应用和合成方法。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477478

H Izumi, S Yamagami, S Futamura

{"title":"1-Azaadamantanes: pharmacological applications and synthetic approaches.","authors":"H Izumi, S Yamagami, S Futamura","doi":"10.2174/1568016033477478","DOIUrl":"https://doi.org/10.2174/1568016033477478","url":null,"abstract":"1-Azaadamantane (1-azatricyclo [3.3.1.1(3,7)]decane) was synthesized in 1953, and the derivatives have been used as rigid models for studies on intramolecular charge transfer phenomena, fluorescence excitation Rydberg states, highly twisted amides, solid electrolyte gas sensors, basicities, and self-organization systems. These structures have also been attracting considerable interest due to their pharmacological activities. The substituted 1-azaadamantanes as conformationally restricted amines have great potential for the therapeutic utilization as anticholinergic agents, serotonergic agents, and squalene synthase inhibitors. However, many steps have been needed for the synthesis of 1-azaadamantanes, and the concise synthetic approaches have been developed. Though double or triple Mannich reactions yield 1-azaadamantanes in moderate yields, the reduction steps are necessary. Our recent research has revealed that trifluoromethanesulfonic anhydride is available for the convenient synthesis of 1-azoniaadamantanes and 1-azaadamantanes without reduction. The new tools for the discovery of novel drugs such as quantitative structure-activity relationship (QSAR) analysis and vibrational circular dichroism (VCD) spectroscopy have also been discussed.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 2","pages":"99-111"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24643517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Design of a genetically modified soybean protein preventing hypertension based on an anti-hypertensive peptide derived from ovalbumin. 以卵白蛋白衍生的抗高血压肽为基础，设计一种预防高血压的转基因大豆蛋白。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477496

Nobuyuki Matoba, Yuko Yamada, Masaaki Yoshikawa

{"title":"Design of a genetically modified soybean protein preventing hypertension based on an anti-hypertensive peptide derived from ovalbumin.","authors":"Nobuyuki Matoba, Yuko Yamada, Masaaki Yoshikawa","doi":"10.2174/1568016033477496","DOIUrl":"https://doi.org/10.2174/1568016033477496","url":null,"abstract":"Food proteins can be a source of various bioactive peptides including such possessing anti-hypertensive activity. While most orally active anti-hypertensive peptides derived from food proteins inhibit the angiotensin I-converting enzyme (ACE), ovokinin (2-7) (RADHPF), a peptide isolated from a chymotryptic digest of ovalbumin, has been shown to induce nitric oxide-dependent vasorelaxation in an isolated mesenteric artery as well as anti-hypertensive effect after oral administration in spontaneously hypertensive rats (SHRs). Rational amino acid replacement lead to the ovokinin (2-7) analog, RPLKPW, which had the highest anti-hypertensive activity among the tested peptides. Furthermore, oral administration (0.1 mg/kg) of the peptide lowered the blood pressure of SHR but not of normotensive Wistar-Kyoto (WKY) rats. In order to develop a novel use of this potent anti-hypertensive peptide for prevention of hypertension, RPLKPW has been genetically introduced into the homologous sequences in soybean beta-conglycinin alpha' subunit by site-directed mutagenesis. The recombinant RPLKPW-incorporated alpha' subunit expressed in E. coil has been shown to exert anti-hypertensive activity after oral administration in SHR. Thus, RPLKPW-incorporated alpha' subunit is the first example of a genetically modified food protein possessing physiological activity based on a bioactive peptide.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 2","pages":"197-202"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016033477496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24644116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Development of peptide inhibitors to block type I and type III collagen-platelet interaction. 阻断I型和III型胶原-血小板相互作用的肽抑制剂的开发。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477504

T M Chiang

{"title":"Development of peptide inhibitors to block type I and type III collagen-platelet interaction.","authors":"T M Chiang","doi":"10.2174/1568016033477504","DOIUrl":"https://doi.org/10.2174/1568016033477504","url":null,"abstract":"Platelet-collagen interaction plays an important role in hemostasis and pathological thrombosis. Upon an injury to the subendothelium of a blood vessel wall, platelets attach to the denuded substrate, aggregate, and release biological substances. Many investigators are trying to explore blocking agents to interrupt the adhesion of platelets to the damaged walls. To this date, extensive studies on developing inhibitors for platelet glycoprotein IIb/IIIa have been conducted. There are many trial reports showing that the efficacy of these antagonists has not completely blocked the adhesion of platelets to the distal site(s) of the injury. Type I and type III collagen are present in abundant amounts in blood vessel walls and other laboratories have obtained various active peptides from collagen molecules to block type I and type III collagen-platelet interaction. We have tried to develop active peptides from platelet receptors for types I and III collagen to aberrant both type I and type III collagen-induced platelet aggregation. We have defined effective and specific peptide inhibitors for each type of collagen to block binding to washed platelets, platelet aggregation. and adhesion of washed platelets to rabbit aortic segments.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 2","pages":"171-5"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24644113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Diadenosine polyphosphates: postulated mechanisms mediating the cardiac effects. 多磷酸二腺苷:介导心脏作用的假设机制。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477513

Brigitte Maria Stavrou

{"title":"Diadenosine polyphosphates: postulated mechanisms mediating the cardiac effects.","authors":"Brigitte Maria Stavrou","doi":"10.2174/1568016033477513","DOIUrl":"https://doi.org/10.2174/1568016033477513","url":null,"abstract":"Diadenosine polyphosphates (Ap(n)A) are naturally occurring molecules which have been identified in human and guinea-pig cardiac tissue and whose physiological role is being established. They are stored in platelet dense granules in a metabolically inactive form. Ap(n)A form a class of dinucleotides, including diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) which have vasopressor actions in some tissues and vasodilator actions in others. Ap(n)A have been reported to interact with receptors distinct from P1 and P2-purinoceptors, and the presence of a unique Ap4A receptor has been demonstrated in isolated ventricular myocytes. Despite the identification of this receptor, other studies suggest that some of the cardiovascular effects are mediated by purinoceptors. Ap(n)A are released from platelet dense granules into the circulation during the platelet release reaction where they can reduce heart rate. The existence of Ap(n)A in myocardial tissue and platelet granules as well as their effects on coronary artery tone and myocardial function suggests a regulatory role for these compounds in the heart. This review describes the effects of Ap(n)A in terms of their coronary vasomotor and cardiac electrophysiological effects. The mechanism responsible for these effects is reviewed; including the involvement of purinergic receptors, the effects of alterations in extracellular pH and the contribution of nitric oxide and prostanoids. Potential pro-arrhythmogenic effects of diadenosine polyphosphates during myocardial ischaemia are also discussed as these compounds could contribute to inhomogeneities of repolarization in ischaemic myocardium.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 2","pages":"151-69"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24644112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

New advances in the field of calcium channel antagonists: cardiovascular effects and structure-activity relationships. 钙通道拮抗剂领域的新进展:心血管效应和构效关系。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-06-01 DOI: 10.2174/1568016033477487

M Romero, I Sánchez, M D Pujol

{"title":"New advances in the field of calcium channel antagonists: cardiovascular effects and structure-activity relationships.","authors":"M Romero, I Sánchez, M D Pujol","doi":"10.2174/1568016033477487","DOIUrl":"https://doi.org/10.2174/1568016033477487","url":null,"abstract":"In the last 15 years, calcium channel blockers have been widely used for treating cardiovascular diseases. These agents are a heterogeneous group of drugs with differing cardiovascular effects, and are effective in the treatment of angina and hypertension. These synthetic compounds bind separately with receptor sites located in or near the calcium channel, at molecular sites still to be fully identified. Verapamil, nifedipine and diltiazem are the most representative calcium channel blockers and used as prototypes for the design and development of new anticalcium molecules with potential efficacy and reduced toxic effects. There are three different types of voltage-operated calcium channels (VOCs): L-type, T-type and N-type, which are considered extra-cellular, but some anti-calcium agents as bepridil possess potential intracellular calcium activity. Many synthetic compounds containing heterocyclic ring in their structures have attracted considerable interest since current studies revealed their mechanisms and sites of action. This article reviews the new advances in the calcium channel antagonist group, showing new structures with longer-acting and higher vascular selectivity.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 2","pages":"113-41"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24644110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 29

Protease-activated receptor-2 antagonists and agonists. 蛋白酶激活受体-2拮抗剂和激动剂。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-03-01 DOI: 10.2174/1568016033356698

Robert M Scarborough

引用次数: 11

Potent non-peptide thrombin receptor antagonists. 有效的非肽凝血酶受体拮抗剂。

Current medicinal chemistry. Cardiovascular and hematological agents Pub Date : 2003-03-01 DOI: 10.2174/1568016033356706

Samuel Chackalamannil, Ho-Sam Ahn, Yan Xia, Darío Doller, Carolyn Foster

{"title":"Potent non-peptide thrombin receptor antagonists.","authors":"Samuel Chackalamannil, Ho-Sam Ahn, Yan Xia, Darío Doller, Carolyn Foster","doi":"10.2174/1568016033356706","DOIUrl":"https://doi.org/10.2174/1568016033356706","url":null,"abstract":"Protease activated receptor-1 (PAR-1), also known as thrombin receptor, is present in a variety of cell types such as platelets and endothelial cells. PAR-1 is proteolytically activated by thrombin by cleavage at its extracellular domain, unmasking a new amino terminus, which internally binds to the proximal receptor, eliciting cellular activation. Inhibition of the cellular activation by thrombin is a potentially promising therapeutic approach for the treatment of thrombotic and vascular proliferative disorders such as atherosclerosis and restenosis. Reported herein is the pharmacology of potent, low molecular weight thrombin receptor antagonists from pyrroloquinazoline, benzimidazole, and himbacine series. In the radioligand binding assay, these compounds inhibited PAR-1 in a competitive manner. They also inhibited thrombin and agonist peptide induced human platelet aggregation in a dose-dependent manner. Additionally, these compounds showed dose-dependent inhibition of agonist-induced cytosolic Ca(+2) transients and thymidine incorporation in human coronary artery smooth muscle cells (hCASMC). The most potent compound among these antagonists showed a Ki of 12 nM in the radioligand binding assay and an IC50 of 70 nM in the platelet aggregation inhibition assay.","PeriodicalId":87078,"journal":{"name":"Current medicinal chemistry. Cardiovascular and hematological agents","volume":"1 1","pages":"37-45"},"PeriodicalIF":0.0,"publicationDate":"2003-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568016033356706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24643151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13