Commercial taxane formulations induce stomatocytosis and increase blood viscosity.

Abstract:

:1. Taxanes are antineoplastic drugs which have cardiovascular side effects of unknown mechanism. We investigated their influence on blood viscosity and erythrocyte morphology. 2. Whole blood was incubated in vitro with increasing concentrations of Taxol, Taxotere, paclitaxel (0-100 microM) and the vehicles Cremophor-EL and Tween 80 (0-5% vol) for 1 h at 37 degrees C. Plasma and whole blood viscosity (Haematocrit 45%) were measured and erythrocyte morphology was assessed on glutaraldehyde-fixed cells. The same investigations were performed in seven patients before and after a Taxol-infusion. 3. Taxol and Taxotere induced a dose- and time-dependent stomatocytic shape transformation of erythrocytes. Paclitaxel alone had no effect, but the vehicles cremophor-EL and Tween 80, used in Taxol and Taxotere, respectively, induced a comparable degree of stomatocytosis. This suggests a preferential intercalation of these substances into the inner hemileaflet of the membrane lipid bilayer. Associated with this shape change a dose-dependent increase in plasma and whole blood viscosity was observed. Neither shape nor viscosity changes were reversible upon removal of the agents. After the infusion of 130-300 mg Taxol in patients a slight shift towards stomatocytosis and an increase in whole blood viscosity at high shear rate from 5.09+/-0.30 to 5.44+/-0.38 mPa.s (P<0.05) were confirmed. 4. Commercial taxane drug formulations induce stomatocytosis and increase blood viscosity, which is due to their formulation vehicles. These findings may contribute to the understanding of the cardiovascular side effects of these drugs.

journal_name

Br J Pharmacol

authors

Mark M,Walter R,Meredith DO,Reinhart WH

doi

10.1038/sj.bjp.0704387

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

1207-14

issue

6

eissn

0007-1188

issn

1476-5381

journal_volume

134

pub_type

杂志文章
  • Endothelium-dependent sensory NANC vasodilatation: involvement of ATP, CGRP and a possible NO store.

    abstract::1 Non-adrenergic non-cholinergic (NANC) vasodilator nerves regulate tone in certain vascular beds. We have investigated the mechanisms of the NANC dilator response in the isolated small mesenteric artery of the rabbit by use of the tension myograph. 2 Small second or third order (150-300 microm in diameter) arteries o...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701610

    authors: Kakuyama M,Vallance P,Ahluwalia A

    更新日期:1998-01-01 00:00:00

  • Cardiovascular effects of a novel, potent and selective phosphodiesterase 5 inhibitor, DMPPO: in vitro and in vivo characterization.

    abstract::1. The aim of this study was to investigate the cardiovascular effects of a novel, potent and specific phosphodiesterase 5 (PDE 5) inhibitor, 1,3 dimethyl-6-(2-propoxy-5-methane sulphonylamidophenyl)-pyrazolo[3,4-d]pyrimidin-4-(5H)-one (DMPPO) in phenylephrine-precontracted rat aortic rings and different in vivo rat p...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1996.tb15548.x

    authors: Delpy E,le Monnier de Gouville AC

    更新日期:1996-07-01 00:00:00

  • Brain alpha(2)-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA.

    abstract::1. This study was designed to assess the molecular and cellular events involved in the up-regulation (and receptor supersensitivity) of brain alpha(2)-adrenoceptors as a result of chronic depletion of noradrenaline (and other monoamines) by reserpine. 2. Chronic reserpine (0.25 mg kg(-1) s.c., every 48 h for 6 - 14 da...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703963

    authors: Ribas C,Miralles A,Busquets X,García-Sevilla JA

    更新日期:2001-04-01 00:00:00

  • Effects of verapamil on the response of the guinea-pig tracheal muscle to carbachol.

    abstract::The effects of verapamil on the contraction of the guinea-pig tracheal smooth muscle induced by calcium (Ca2+) or barium (Ba2+) were investigated in three different conditions: (a) in excess K solution, (b) in the presence of carbachol, and (c) in excess K solution containing carbachol. In order to clarify the contrac...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1986.tb10222.x

    authors: Baba K,Satake T,Takagi K,Tomita T

    更新日期:1986-06-01 00:00:00

  • Inhibitors of catechol-O-methyltransferase sensitize mice to pain.

    abstract:BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) inhibitors are used in Parkinson's disease in which pain is an important symptom. COMT polymorphisms modulate pain and opioid analgesia in humans. In rats, COMT inhibitors have been shown to be pro-nociceptive in acute pain models, but also to attenuate allodyn...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.00999.x

    authors: Kambur O,Talka R,Ansah OB,Kontinen VK,Pertovaara A,Kalso E,Männistö PT

    更新日期:2010-12-01 00:00:00

  • An examination of 5-hydroxytryptamine receptors in human saphenous vein.

    abstract::We have examined the effects of antagonists on the isometric contraction of the human saphenous vein produced by 5-hydroxytryptamine (5-HT). The 5-HT2-antagonist ketanserin (1 microM) had little effect on the lower part of the concentration-response curve to 5-HT, but markedly shifted the upper part of the curve. Yohi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1986.tb11122.x

    authors: Docherty JR,Hyland L

    更新日期:1986-09-01 00:00:00

  • Modification of dyskinesias following the intrastriatal injection of prostaglandins in the rodent.

    abstract::The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2 alpha to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea-pig. Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1985.tb11095.x

    authors: Costall B,Holmes SW,Kelly ME,Naylor RJ

    更新日期:1985-08-01 00:00:00

  • Involvement of Rac1 signalling pathway in the development and maintenance of acute inflammatory pain induced by bee venom injection.

    abstract:BACKGROUND AND PURPOSE:The Rho GTPase, Rac1, is involved in the pathogenesis of neuropathic pain induced by malformation of dendritic spines in the spinal dorsal horn (sDH) neurons. In the present study, the contribution of spinal Rac1 to peripheral inflammatory pain was studied. EXPERIMENTAL APPROACH:Effects of s.c. ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13413

    authors: Wang Y,Lu YF,Li CL,Sun W,Li Z,Wang RR,He T,Yang F,Yang Y,Wang XL,Guan SM,Chen J

    更新日期:2016-03-01 00:00:00

  • Mechanism of dexamphetamine-induced mydriasis in the anaesthetized rat.

    abstract::1. The effect of intravenous administration of dexamphetamine [+)-Amp) on rat pupil diameter was investigated. In all experiments, the vagosympathetic trunks were sectioned bilaterally at the cervical level. 2. In rats anaesthetized with urethane, (+)-Amp (0.1-0.3 mg kg-1, i.v.) produced a dose-related increase in pup...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1989.tb11781.x

    authors: Hey JA,Ito T,Koss MC

    更新日期:1989-01-01 00:00:00

  • Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors.

    abstract::1. Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)1 receptor antagonists a...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702698

    authors: Sakurada T,Katsuyama S,Sakurada S,Inoue M,Tan-No K,Kisara K,Sakurada C,Ueda H,Sasaki J

    更新日期:1999-08-01 00:00:00

  • Pharmacological significance of biogenic amines in the lungs: noradrenaline and dopamine.

    abstract::1. The noradrenaline concentration in the lung was less than 0.5 mug/g in eight animal species.2. In the cat, dog, rabbit and goat, tyramine produced a fall in pulmonary resistance, which was reduced by the administration of either reserpine or cocaine. Although an infusion of noradrenaline increased the content of th...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1970.tb08525.x

    authors: Aviado DM,Sadavongvivad C

    更新日期:1970-02-01 00:00:00

  • Airway reactivity, inflammatory cell influx and nitric oxide in guinea-pig airways after lipopolysaccharide inhalation.

    abstract::1. The aim of this study was to investigate the relationship between airway reactivity, leukocyte influx and nitric oxide (NO), in conscious guinea-pigs after aerosolized lipopolysaccharide (LPS) exposure. 2. Inhaled histamine (1 mM, 20 s), causing no bronchoconstriction before LPS exposure (30 microg ml(-1), 1 h), ca...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703589

    authors: Toward TJ,Broadley KJ

    更新日期:2000-09-01 00:00:00

  • The effects of alpha 2-adrenoceptor antagonists on the inhibition of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shakes by 5-HT1A receptor agonists in the mouse.

    abstract::1. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), gepirone, buspirone and ipsapirone dose-dependently antagonized the head-shakes induced by 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane hydrochloride (DOI) (1.0 mg kg-1) in mice, when these agents were given i.p. 10 min beforehand. 2. para-Chlorophenylalanine (...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1993.tb13727.x

    authors: Dursun SM,Handley SL

    更新日期:1993-08-01 00:00:00

  • Beta-adrenoceptor mediated facilitation of noradrenaline and adenosine 5'-triphosphate release from sympathetic nerves supplying the rat tail artery.

    abstract::1. The effects of prejunctional beta-adrenoceptor activation on electrically evoked noradrenaline (NA) and adenosine 5'-triphosphate (ATP) were studied by use of continuous amperometry and conventional intracellular recording techniques. Excitatory junction potentials (e.j.ps) were used as a measure of ATP release, an...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0700959

    authors: Brock JA,Bridgewater M,Cunnane TC

    更新日期:1997-03-01 00:00:00

  • Diltiazem-induced vasodilatation of smooth muscle cells of the canine basilar artery.

    abstract::1 The effects of diltiazem on smooth muscle cells of the canine basilar artery were investigated by means of microelectrode, double sucrose gap and isometric tension recording methods. 2 The mean membrane potential of the smooth muscle cells was -49.8 mV and they were electrically quiescent. Diltiazem (over 10(-5) M) ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1982.tb09162.x

    authors: Fujiwara S,Ito Y,Itoh T,Kuriyama H,Suzuki H

    更新日期:1982-03-01 00:00:00

  • Gastric mucosal damage induced by local intra-arterial administration of Paf in the rat.

    abstract::1. A technique for the close-arterial administration of substances to the rat stomach in vivo has been developed. 2. Intra-arterial infusion of platelet-activating factor (Paf, 10-50 ng kg-1 min-1 for 10 min) induced macroscopically assessed damage in the corpus mucosa, characterized as vasocongestion and necrosis. 3....

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1988.tb11425.x

    authors: Esplugues JV,Whittle BJ

    更新日期:1988-01-01 00:00:00

  • Potentiation by nitric oxide of the ATP-sensitive K+ current induced by K+ channel openers in guinea-pig ventricular cells.

    abstract::1. Modulation by nitric oxide (NO) of the ATP-sensitive K+ channel (KATP) current (IK(ATP)) was investigated in single ventricular cells dissociated from guinea-pig hearts. IK(ATP) was induced by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine+ ++ (KRN4884) and cromakalim. 2. In the whole-cell pat...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701069

    authors: Shinbo A,Iijima T

    更新日期:1997-04-01 00:00:00

  • Characterization of the postjunctional alpha 2C-adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins.

    abstract:BACKGROUND AND PURPOSE:In terms of postjunctional alpha(2)-adrenoceptors in the pulmonary circulation, no evidence is available with regard to the receptor subtypes mediating vasoconstriction. Therefore, we characterized the alpha(2)-adrenoceptor subtypes mediating contraction in isolated porcine pulmonary veins. EXPE...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0707221

    authors: Görnemann T,von Wenckstern H,Kleuser B,Villalón CM,Centurión D,Jähnichen S,Pertz HH

    更新日期:2007-05-01 00:00:00

  • Potential importance of alterations in hydrogen sulphide (H2S) bioavailability in diabetes.

    abstract::Despite its long-standing reputation as a foul smelling and toxic gas that is associated with the decay of biological matter,hydrogen sulphide (H2S) has emerged as an important regulator of cardiovascular homoeostasis. H2S promotes a number of cellular signals that regulate metabolism, cardiac function and cell surviv...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/bjp.2008.359

    authors: Lefer DJ

    更新日期:2008-11-01 00:00:00

  • Release of gamma-aminobutyric acid and acetylcholine by neurotensin in guinea-pig ileum.

    abstract::The release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) from the strips of guinea-pig ileum was investigated in the presence of neurotensin. Neurotensin evoked the release of [3H]-GABA from the strips preloaded with [3H]-GABA, and the evoked release was Ca2+-dependent and tetrodotoxin-sensitive. Hexameth...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1987.tb11204.x

    authors: Nakamoto M,Tanaka C,Taniyama K

    更新日期:1987-03-01 00:00:00

  • Investigation of the interaction between nitric oxide and vasoactive intestinal polypeptide in the guinea-pig gastric fundus.

    abstract::The interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) was investigated in isolated circular smooth muscle cells and strips of the guinea-pig gastric fundus. VIP induced a concentration-dependent inhibition of carbachol-induced contraction in smooth muscle cells with a maximum at 10(-6) ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703089

    authors: Dick JM,Van Geldre LA,Timmermans JP,Lefebvre RA

    更新日期:2000-02-01 00:00:00

  • The application of 'omics' to pulmonary arterial hypertension.

    abstract::Recent genome-wide analyses of rare and common sequence variations have brought greater clarity to the genetic architecture of pulmonary arterial hypertension and implicated novel genes in disease development. Transcriptional signatures have been reported in whole lung tissue, pulmonary vascular cells and peripheral c...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.15056

    authors: Harbaum L,Rhodes CJ,Otero-Núñez P,Wharton J,Wilkins MR

    更新日期:2021-01-01 00:00:00

  • Mediation of the hypotensive action of systemic clonidine in the rat by alpha 2-adrenoceptors.

    abstract::1. During the past few years it has been shown that the sympatholytic effect resulting from localized microinjection of clonidine and other imidazolines into the rostral ventrolateral medulla (RVL) results from activation of 'imidazoline' receptors (I1 receptors) rather than from an alpha 2-adrenoceptor-mediated effec...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1993.tb14012.x

    authors: Hieble JP,Kolpak DC

    更新日期:1993-12-01 00:00:00

  • Effects of a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)phenoxy]2-methyl propionic acid (alpha-1081) on biliary lipid secretion in rats.

    abstract::1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of chol...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1981.tb10471.x

    authors: Aldini R,Barbara L,Benelli A,Borzatta V,Geminiani S,Mascellani G,Morselli A,Roda A,Roda E

    更新日期:1981-11-01 00:00:00

  • Dopamine receptor-mediated spinal antinociception in the normal and haloperidol pretreated rat: effects of sulpiride and SCH 23390.

    abstract::Nociceptive tail flick latencies (TFL) were recorded in response to noxious thermal stimuli applied to lightly anaesthetized rats. The effects of intrathecally administered dopamine receptor agonists alone and combined with dopamine receptor antagonists were examined upon the TFL. Experiments were repeated on animals ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1987.tb16820.x

    authors: Barasi S,Ben-Sreti MM,Clatworthy AL,Duggal KN,Gonzalez JP,Robertson J,Rooney KF,Sewell RD

    更新日期:1987-01-01 00:00:00

  • Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea-pig ventricular cells.

    abstract::1. The effects of diprafenone and propafenone on transmembrane action potential were examined and compared in papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, both diprafenone and propafenone > or = 10(-6) M caused a significant and dose-dependent decrease in ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1992.tb14529.x

    authors: Kodama I,Suzuki R,Honjo H,Toyama J

    更新日期:1992-11-01 00:00:00

  • Evidence against the unitary hypothesis of agonist and antagonist action at presynaptic adrenoceptors.

    abstract::1 The concept that presynaptic receptors regulate noradrenergic transmitter release via a system of inhibitory receptors mediating negative feedback relies on a supposed association between increases in stimulation-induced efflux of [3H]-noradrenaline by antagonists and blockade by them of the inhibitory effects of ex...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1982.tb09308.x

    authors: Kalsner S

    更新日期:1982-10-01 00:00:00

  • Synergistic inhibition by BQ-123 and BQ-788 of endothelin-1-induced contractions of the rabbit pulmonary artery.

    abstract::In the rabbit isolated pulmonary artery, neither the ETA receptor antagonist, BQ-123 (10 microM), nor the ETB receptor antagonist, BQ-788 (10 microM), inhibited the contractions induced by 1 nM endothelin-1 (ET-1). However, the combination of BQ-123 and BQ-788 completely inhibited the ET-1-induced contraction. In cont...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1994.tb16901.x

    authors: Fukuroda T,Ozaki S,Ihara M,Ishikawa K,Yano M,Nishikibe M

    更新日期:1994-10-01 00:00:00

  • Modulation of the apelin/APJ system in heart failure and atherosclerosis in man.

    abstract:BACKGROUND AND PURPOSE:The aim of this study was to determine whether the apelin/APJ system is altered in human cardiovascular disease by investigating whether the expression of apelin or its receptor is altered at the protein level. EXPERIMENTAL APPROACH:Radioligand binding studies were used to determine apelin recep...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.00821.x

    authors: Pitkin SL,Maguire JJ,Kuc RE,Davenport AP

    更新日期:2010-08-01 00:00:00

  • Cyclic AMP-mediated regulation of vascular smooth muscle cell cyclic AMP phosphodiesterase activity.

    abstract::1. Rat cultured aortic vascular smooth muscle cells (VSMC) express both cyclic GMP-inhibited cyclic AMP phosphodiesterase (PDE3) and Ro 20-1724-inhibited cyclic AMP phosphodiesterase (PDE4) activities. By utilizing either cilostamide, a PDE3-selective inhibitor, or Ro 20-1724, a PDE4-selective inhibitor, PDE3 and PDE4...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701376

    authors: Rose RJ,Liu H,Palmer D,Maurice DH

    更新日期:1997-09-01 00:00:00