Azithromycin inhibits muscarinic 2 receptor-activated and voltage-activated Ca2+ permeant ion channels and Ca2+ sensitization, relaxing airway smooth muscle contraction.


:Azithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch-clamp techniques. AZM completely inhibited acetylcholine (ACH)-induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L-type voltage-dependent Ca2+ channels (LVDCCs)), Pyr3 (selective inhibitor of TRPC3 and/or STIM/Orai channels, which are nonselective cation channels (NSCCs)), and Y-27632 (selective inhibitor of Rho-associated kinase (ROCK)). Moreover, LVDCC- and NSCC-mediated currents were inhibited by AZM, and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca2+ permeant ion channels, M2 receptors, and TRPC3 and/or STIM/Orai, which decreased cytosolic Ca2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD.


Wang Q,Yu MF,Zhang WJ,Liu BB,Zhao QY,Luo X,Xu H,She YS,Zang DA,Qiu JY,Shen J,Peng YB,Zhao P,Xue L,Chen W,Ma LQ,Nie X,Shen C,Chen S,Chen S,Liu Q,Dai J,Qin G,Zheng YM,Wang YX,ZhuGe R,Chen J,Liu QH




Has Abstract


2019-04-01 00:00:00












  • Effect of ATP on Ca2+ uptake in the presence of high glucose in renal proximal tubule cells.

    abstract::1. Calcium regulation has been reported to be associated with the development of diabetic nephropathy. Thus, changes in Ca2+ uptake induced by ATP, an important regulator of Ca2+ uptake, in the diabetic condition and related signal pathways were examined in primary cultures of rabbit renal proximal tubule cells (PTC)....

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Han HJ,Park SH,Lee YJ,Lee JC,Lee JH

    更新日期:2003-09-01 00:00:00

  • Barriers to successful delivery of short interfering RNA after systemic administration.

    abstract::1. RNA interference in vivo has tremendous potential, both with respect to the elucidation of protein function in animals and as a therapeutic platform in humans. In vitro, short interfering RNA (siRNA) has been shown to completely silence gene expression in mammalian cells at low picomolar concentrations. 2. Although...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: White PJ

    更新日期:2008-11-01 00:00:00

  • Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells.

    abstract::1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders. 2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Wong KL,Chan P,Huang WC,Yang TL,Liu IM,Lai TY,Tsai CC,Cheng JT

    更新日期:2003-10-01 00:00:00

  • Functional diversity of mammalian type 2C protein phosphatase isoforms: new tales from an old family.

    abstract::1. The Type 2C protein phosphatases (PP2C) represent a highly conserved gene family in the mammalian genome. Recent studies have revealed that PP2C isoforms possess unique patterns of tissue and subcellular distribution associated with diverse functionalities. 2. The functional importance of PP2C isoforms has been sho...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Lu G,Wang Y

    更新日期:2008-02-01 00:00:00

  • Effect of acute and subacute treatment of clonidine on blood pH, PCO2 and PO2 in mice.

    abstract::1. Measurements were made on blood pH, PCO2 and PO2 in mice after a single injection and following five weeks continuous clonidine hydrochloride treatment. 2. A single injection of clonidine hydrochloride exerts no effect on blood pH, PCO2 and PO2 but five weeks of continuous clonidine hydrochloride treatment lowers t...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Gan EK,Abdul Sattar MZ

    更新日期:1982-11-01 00:00:00

  • Hypoxia-inducible factor 1 alpha and nuclear-related receptor 1 as targets for neuroprotection by albendazole in a rat rotenone model of Parkinson's disease.

    abstract::Hypoxia-inducible factor-1 alpha (HIF-1α) and nuclear receptor related-1 (Nurr1) play pivotal roles in the development and survival of dopaminergic neurons, and deficiencies in these genes may be involved in Parkinson's disease (PD) pathogenesis. Recently, anthelminthic benzimidazoles were shown to promote HIF-1α tran...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Kandil EA,Sayed RH,Ahmed LA,Abd El Fattah MA,El-Sayeh BM

    更新日期:2019-12-01 00:00:00

  • The association between serum albumin/prealbumin level and disease severity in non-CF bronchiectasis.

    abstract::Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disease that can lead to malnutrition. Serum prealbumin and albumin level are related to inflammatory and nutritional status. Thus, we aimed to confirm our hypothesis that low serum albumin and prealbumin level, as well as body mass index (BMI), is cor...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Li L,Li Z,Bi J,Li H,Wang S,Shao C,Song Y

    更新日期:2020-09-01 00:00:00

  • Ghrelin gene-related peptides: multifunctional endocrine / autocrine modulators in health and disease.

    abstract::1. Ghrelin is a multifunctional peptide hormone that affects various processes, including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation. Ghrelin is produced in the stomach and in other normal and pathological cell types. It may act as an endocrine or au...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Seim I,Amorim L,Walpole C,Carter S,Chopin LK,Herington AC

    更新日期:2010-01-01 00:00:00

  • Modulation of the orthostatic blood pressure response by acute nitrate consumption is dependent upon ethnic origin.

    abstract::Orthostatic stress triggers a response to maintain cerebral perfusion and prevent syncope. Given the hypotensive effects of inorganic nitrate this response to orthostasis may be altered by acute supplementation with inorganic nitrate and modified by ethnic origin. Caucasian and SE Asian (n = 30 for both), were recruit...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Allen K,Chuter KM,Fithon K,Marshall L,Hauton D

    更新日期:2018-11-01 00:00:00

  • Propofol block of cardiac sodium currents in rat isolated myocardial cells is increased at depolarized resting potentials.

    abstract::1. The effect of propofol on cardiac whole-cell sodium currents and single sodium channels in rat isolated ventricular myocytes was examined using patch-clamp techniques. 2. Propofol caused a block of the whole-cell sodium current, the potency of block depending on the holding potential. When cells were held at -90 mV...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Saint DA,Tang Y

    更新日期:1998-05-01 00:00:00

  • Cardiovascular status following combined angiotensin-converting enzyme and AT1 receptor inhibition in conscious spontaneously hypertensive rats.

    abstract::1. Combined treatment of spontaneously hypertensive rats (SHR) with AT1 receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors has been shown to reduce mean arterial pressure (MAP) more than monotherapy with either agent. The aims of the present study were to investigate the effects of chronic dual re...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Duke LM,Paull JR,Widdop RE

    更新日期:2003-05-01 00:00:00

  • An investigation of the influence of patient-related factors and comedications on lamotrigine clearance in patients with epilepsy.

    abstract::Lamotrigine (LTG) is one of the most widely used antiepileptic drugs. Confusion still exists in the literature as to the relative influence of age, body weight, and concomitant drug therapy on LTG pharmacokinetics. So, the objective of this study is to evaluate the influence of patient-related factors and comedication...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Baldoni AO,Freitas-Lima P,de Santi Ferreira FI,Martinez EZ,Queiroz RH,Sakamoto AC,Alexandre V,Perucca E,Pereira LR

    更新日期:2016-07-01 00:00:00

  • Recombinant human hepatocyte growth factor (HGF), but not rat HGF, elicits glomerular injury and albuminuria in normal rats via an immune complex-dependent mechanism.

    abstract::1. Hepatocyte growth factor (HGF) has the therapeutic potential to improve renal fibrosis and proteinuria in rodents with chronic kidney disease. In contrast, long-term administration of human HGF to normal rats reportedly elicits proteinuria. Thus, the role of HGF during proteinuria remains contentious. The aim of th...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Mizuno S,Ikebuchi F,Fukuta K,Kato T,Matsumoto K,Adachi K,Abe T,Nakamura T

    更新日期:2011-03-01 00:00:00

  • Reduced store-operated Ca2+ entry impairs mesenteric artery function in response to high external glucose in type 2 diabetic ZDF rats.

    abstract::Diabetes is a major risk factor for cardiovascular disease, affecting both endothelial and smooth muscle cells. Store-operated Ca2+ channels (SOCCs) have been implicated in many diabetic complications. Vascular dysfunction is common in patients with diabetes, but the role of SOCCs in diabetic vasculopathy is still unc...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Schach C,Wester M,Leibl F,Redel A,Gruber M,Maier LS,Endemann D,Wagner S

    更新日期:2020-07-01 00:00:00

  • Neuropharmacology of nicotine: effects on the autoregulation of acetylcholine release by substance P and methionine enkephalin in rodent cerebral slices and toxicological implications.

    abstract::1. The neuronal release of acetylcholine (ACh) and its autoregulation by neuromodulators, substance P (SP) and methionine enkephalin (MEK), have been studied using superfused rodent cerebral slices. Nicotine exerts significant effects on autoregulation of ACh release, which may have toxicological implications. 2. Posi...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Sastry BV

    更新日期:1995-04-01 00:00:00

  • Attenuation of the antihypertensive effect of captopril by the opioid receptor antagonist naloxone.

    abstract::To test a possible role of endogenous opioids in the blood pressure (BP) and heart rate (HR) responses to the converting enzyme inhibitor captopril in man, nine normal subjects were given captopril (50 mg) or placebo with and without the opioid antagonist naloxone (0.2 mg/kg i.v.). Treatments were given in random orde...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Millar JA,Sturani A,Rubin PC,Lawrie C,Reid JL

    更新日期:1983-05-01 00:00:00

  • Responses of the dural circulation to electrical stimulation of the trigeminal ganglion in the cat.

    abstract::1. In cats anaesthetized with alpha-chloralose, electrical stimulation (ES) of the trigeminal ganglion produced a fall in blood pressure, a predominantly ipsilateral dilatation in the common carotid vascular bed and bilateral dilatation of the middle meningeal vascular bed. Section of the trigeminal root abolished the...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Lambert GA,Michalicek J,Regaglia F

    更新日期:1997-06-01 00:00:00

  • Elevation of blood pressure in hypertensive rats after lesioning serotonin nerves in the dorsomedial medulla oblongata.

    abstract::The possibility that serotonin (5HT) nerve endings in the dorsomedial medulla oblongata participate in the control of blood pressure was investigated in stroke-prone hypertensive rats and in normotensive rats. 5HT nerves were destroyed by injecting 5,7-dihydroxytryptamine bilaterally into the solitary tract nucleus. I...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Howe PR,Rogers PF,King RA,Smith RM

    更新日期:1983-05-01 00:00:00

  • Female, but not male, mice show delayed cutaneous wound healing following aspirin administration.

    abstract::Cyclo-oxygenase (COX) is an enzyme that participates in the wound healing process. Aspirin, a non-steroidal anti-inflammatory drug, simultaneously inhibits the aromatase activity of COX-1 and COX-2 isoforms, which is needed for prostaglandin synthesis. The aim of the present study was to determine whether aspirin, and...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: dos Santos JS,Monte-Alto-Costa A

    更新日期:2013-02-01 00:00:00

  • The CGP7930 analogue 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP) potentiates baclofen action at GABA(B) autoreceptors.

    abstract::The pharmacological actions of 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP), a putative presynaptic GABA(B) receptor modulator, were examined in electrically stimulated rat neocortical brain slices preloaded with [3H]-GABA or [3H]-glutamic acid. At 10 mmol/L, BSPP inhibited the release of [3H]-GAB...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Parker DA,Marino V,Ong J,Puspawati NM,Prager RH

    更新日期:2008-09-01 00:00:00

  • Mechanisms of lidocaine actions on normal and abnormal rhythms in canine cardiac tissues in vivo and in vitro.

    abstract::1. The actions of lidocaine on cardiac pacemaker rhythms were studied in anaesthetized dogs and in Purkinje fibres from hearts of the same animals. 2. In vivo, lidocaine (1 mg/kg, intravenously) slowed the sino-atrial (SA) node rhythm (-5.0%), and (during vagal stimulation) prolonged ventricular standstill by +25.1% a...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Abete P,Ferrara N,Rengo F,Vassalle M

    更新日期:1991-03-01 00:00:00

  • Renal prostaglandin efflux induced by vasopressin, dDAVP and arachidonic acid: contrasting profile and sites of release.

    abstract::Prostaglandin (PG) efflux into ureteral (UE) and venous effluents (VE) of rabbit isolated perfused kidneys was determined by superfusion bioassay and radioimmunoassay (RIA), in response to injections of arginine-vasopressin (AVP), the non-pressor vasopressin analogue 1-deamino-8-D-arginine vasopressin (dDAVP) and arac...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Miller MJ,Westlin WF,McNeill H,McGiff JC

    更新日期:1986-08-01 00:00:00

  • Chronic kidney disease growth factors in renal fibrosis.

    abstract::1. The common pathological alteration in virtually every progressive chronic kidney disease (CKD) is renal fibrosis. 2. This review focuses on some growth factors, which are particularly well-established in contributing to fibrosis, such as the profibrotic, transforming growth factor-β, and connective tissue growth fa...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Boor P,Floege J

    更新日期:2011-07-01 00:00:00

  • Glycyrrhizin treatment ameliorates post-traumatic stress disorder-like behaviours and restores circadian oscillation of intracranial serotonin.

    abstract::Post-traumatic stress disorder (PTSD) has become a major disease that threatens human health. Neurotransmitters and the amygdala are found to be critical in the development and maintenance of PTSD. We aim to investigate the role of glycyrrhizin in treating PTSD. Contextual fear extinction and elevated plus maze test w...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Lai S,Shi L,Jiang Z,Lin Z

    更新日期:2020-01-01 00:00:00

  • Lack of effect of age on the cardiovascular response to neuropeptide Y injection in the rat nucleus tractus solitarius.

    abstract::1. Neuropeptide Y (NPY) is colocalized with catecholamines in central regions involved in blood pressure regulation and exerts depressor responses in the nucleus tractus solitarius (NTS). Ageing is accompanied by a decline in baroreflex function and a reduction in NPY concentrations in some brain areas. The present st...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Morris MJ,Pavia JM

    更新日期:1997-02-01 00:00:00

  • Asymmetric dimethylarginine does not inhibit arginase activity and is pro-proliferative in pulmonary endothelial cells.

    abstract::Asymmetric dimethylarginine (ADMA) is an endogenously produced nitric oxide synthase (NOS) inhibitor. L-Arginine can be metabolised by NOS and arginase, and arginase is the first step in polyamine production necessary for cellular proliferation. We tested the hypothesis that ADMA would inhibit NOS but not arginase act...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Chen B,Strauch K,Jin Y,Cui H,Nelin LD,Chicoine LG

    更新日期:2014-07-01 00:00:00

  • Effect of labetalol on human platelet function.

    abstract::1. The effects of the alpha-beta-adrenergic antagonist labetalol on the activation of human platelets by adrenaline and other aggregating stimuli have been investigated. 2. Labetalol inhibited platelet aggregation and secretion induced by collagen and the second phase of aggregation caused by ADP, platelet activating ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Anfossi G,Trovati M,Lanzio M,Mularoni E,Massucco P,Emanuelli G

    更新日期:1988-06-01 00:00:00

  • Effects of reserpine pretreatment on neuroeffector transmission in the vas deferens.

    abstract::1. The effects of reserpine pretreatment on neurotransmission in the guinea-pig vas deferens have been re-examined with a view to study the role of noradrenaline (NA) in mediating postjunctional electrical responses and, in particular, excitatory junction potentials (EJP). 2. Reserpine (5 mg/kg, i.p.) caused almost to...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Cunnane TC,Manchanda R

    更新日期:1989-06-01 00:00:00

  • Endothelin stimulates inositol phosphate accumulation in rat right and left atria: a comparison with noradrenaline.

    abstract::1. The effect of endothelin on phosphatidylinositol turnover in rat atria was investigated by measuring the generation of inositol phosphates following [3H]-inositol labelling. 2. In the presence of 10 mmol/L LiCl, endothelin caused dose-dependent increases in the accumulation of inositol mono, bis and trisphosphates ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Kuraja IJ,Woodcock EA

    更新日期:1990-04-01 00:00:00

  • Taurine prevents high-fat diet-induced-hepatic steatosis in rats by direct inhibition of hepatic sterol regulatory element-binding proteins and activation of AMPK.

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Morsy MD,Aboonq MS,ALsleem MA,Abusham AA

    更新日期:2020-07-21 00:00:00