Multiple actions of glaucine on cyclic nucleotide phosphodiesterases, alpha 1-adrenoceptor and benzothiazepine binding site at the calcium channel.

Abstract:

:1. In the present study, the properties of glaucine (an aporphine structurally related to papaverine) were compared with those of papaverine, diltiazem, nifedipine and prazosin. The work includes functional studies on rat isolated aorta contracted with noradrenaline, caffeine or KCl, and a determination of the affinity of glaucine at calcium channel binding sites of alpha-adrenoceptors, by use of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The effects of glaucine on the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta were also determined. 2. Contraction evoked by noradrenaline (1 microM) or depolarizing solution (60 mM KCl) were inhibited in a concentration-dependent manner by all the compounds tested. As expected, prazosin showed a greater selectivity of action on NA-induced contraction, whereas nifedipine and diltiazem appeared more potent on KCl-induced contraction. Glaucine had a greater potency on the contraction elicited by noradrenaline whereas papaverine acted non specifically. 3. In Ca(2+)-free solution, prazosin (0.1 microM) and glaucine (0.1 mM) inhibited the contraction evoked by NA; diltiazem (0.1 mM) diminished this contraction whereas nifedipine (1 microM) had no effect. Preincubation of tissues with glaucine, diltiazem, nifedipine and prazosin did not modify the contractile response induced by caffeine. In contrast, papaverine (0.1 mM) significantly inhibited the contractions evoked by NA or caffeine in Ca(2+)-free medium. 4. Glaucine and papaverine show affinity at the [3H]-prazosin binding site and at the benzothiazepine binding site of the Ca(2+)-channel receptor complex, but have no effect at the dihydropyridine binding site in rat cerebral cortex. Glaucine exerts some selectivity as an inhibitor of [3H]-prazosin binding as opposed to [3H]-(+ )-cis-diltiazem binding while papaverine appears to have approximately equal affinity in this respect.5. This study confirms the presence of four phosphodiesterase (PDE) activities in bovine aorta: a calmodulin-activated PDE (CaM-PDE type I) which hydrolyzed preferentially guanosine 3':5'-cyclic monophosphate (cyclic GMP); a cyclic GMP selective form (cGMP-PDE type V); and two low Km adenosine 3':5'-cyclic monophosphate (cyclic AMP) PDEs that are insensitive to the stimulatory effect of CaM, one of which was inhibited by cyclic GMP (CGI-PDE, type III) and the other by rolipram (cAMP-PDE, type IV). Glaucine selectively inhibits one of the two forms of Ca2+-independent low Km cAMP-PDE, the type IV. In contrast, papaverine exerts a non-selective inhibitory effect upon all PDE forms.6. The present work provides evidence that glaucine, a benzyltetrahydroisoquinoline alkaloid, has interesting properties as an alpha l-adrenoceptor antagonist, calcium entry blocker (through the benzothiazepine recognition site in the calcium channel) and as a selective inhibitor of the rolipram-sensitive cAMP-PDE, type IV PDE.

journal_name

Br J Pharmacol

authors

Ivorra MD,Lugnier C,Schott C,Catret M,Noguera MA,Anselmi E,D'Ocon P

doi

10.1111/j.1476-5381.1992.tb14345.x

subject

Has Abstract

pub_date

1992-06-01 00:00:00

pages

387-94

issue

2

eissn

0007-1188

issn

1476-5381

journal_volume

106

pub_type

杂志文章
  • Contractile effects by intracellular angiotensin II via receptors with a distinct pharmacological profile in rat aorta.

    abstract::1. We studied the effect of intracellular angiotensin II (Ang II) and related peptides on rat aortic contraction, whether this effect is pharmacologically distinguishable from that induced by extracellular stimulation, and determined the Ca2+ source involved. 2. Compounds were delivered into the cytoplasm of de-endoth...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702421

    authors: Brailoiu E,Filipeanu CM,Tica A,Toma CP,de Zeeuw D,Nelemans SA

    更新日期:1999-03-01 00:00:00

  • IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle.

    abstract::Growing evidence suggests that interleukin (IL)-13, a Th2-type cytokine, plays a critical role in the development of bronchial hyper-responsiveness (BHR), an essential feature of asthma, although the underlying mechanisms remain unknown. In the present study, we investigated whether IL-13 directly affects airway smoot...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705558

    authors: Tliba O,Deshpande D,Chen H,Van Besien C,Kannan M,Panettieri RA Jr,Amrani Y

    更新日期:2003-12-01 00:00:00

  • Antagonism of synaptic potentials in ventral horn neurones by 6-cyano-7-nitroquinoxaline-2,3-dione: a study in the rat spinal cord in vitro.

    abstract::1. The rat spinal cord in vitro has been used to assess the effect of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on the dorsal root evoked extracellular ventral root reflex (DR-VRR) and the intracellular excitatory postsynaptic potential (e.p.s.p.) in ventral horn neurones and motoneurones. 2. CNQX (1-5 microM) produ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1992.tb12754.x

    authors: King AE,Lopez-Garcia JA,Cumberbatch M

    更新日期:1992-10-01 00:00:00

  • Reperfusion and calculated RISKs: pharmacological postconditioning of human myocardium.

    abstract::The last five years have witnessed a remarkable resurgence of interest in myocardial reperfusion injury. Reperfusion is absolutely essential to salvage ischaemic myocardium but experimental and clinical studies show that reperfusion-associated injury may mask the full benefits of prompt reperfusion in acute myocardial...

    journal_title:British journal of pharmacology

    pub_type: 评论,杂志文章

    doi:10.1038/sj.bjp.0707498

    authors: Baxter GF,Burley DS

    更新日期:2008-01-01 00:00:00

  • A cerebral nitrergic pathway modulates endotoxin-induced changes in gastric motility.

    abstract::1. This study analyses the neural pathway involved in the modulation of gastric motor function by stress. 2. Systemic administration of low doses of endotoxin (40 microg kg(-1), i.v.) prevents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg kg(-1), i.v., 2-DG) in urethane-anaesthetized rats. 3. Funct...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704258

    authors: Quintana E,García-Zaragozá E,Martínez-Cuesta MA,Calatayud S,Esplugues JV,Barrachina MD

    更新日期:2001-09-01 00:00:00

  • Effects of prostaglandins and nitric oxide on the renal effects of angiotensin II in the anaesthetized rat.

    abstract::1. The potential influences of nitric oxide (NO) and prostaglandins on the renal effects of angiotensin II (Ang II) have been investigated in the captopril-treated anaesthetized rat by examining the effect of indomethacin or the NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), on the renal respo...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702003

    authors: Clayton JS,Clark KL,Johns EJ,Drew GM

    更新日期:1998-08-01 00:00:00

  • Cutaneous reactions to intradermal prostaglandins.

    abstract::1. The effects of intradermally injected prostaglandins (PGs) E(1), E(2), F(1alpha) and F(2alpha) have been examined in the rat and in man.2. PGE(1) and PGE(2) caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, b...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1971.tb09934.x

    authors: Crunkhorn P,Willis AL

    更新日期:1971-01-01 00:00:00

  • Enhancement by GABA of the association rate of picrotoxin and tert-butylbicyclophosphorothionate to the rat cloned alpha 1 beta 2 gamma 2 GABAA receptor subtype.

    abstract::1. We examined how gamma-aminobutyric acid (GABA) influences interaction of picrotoxin and tert-butylbicyclophosphorothionate (TBPS) with recombinant rat alpha 1 beta 2 gamma 2 GABAA receptors stably expressed in human embryonic kidney cells (HEK293), as monitored with changes in Cl- currents measured by the whole-cel...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb16368.x

    authors: Dillon GH,Im WB,Carter DB,McKinley DD

    更新日期:1995-06-01 00:00:00

  • No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block.

    abstract:BACKGROUND & PURPOSE:The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706900

    authors: Thomsen MB,Beekman JD,Attevelt NJ,Takahara A,Sugiyama A,Chiba K,Vos MA

    更新日期:2006-12-01 00:00:00

  • Inhibition of aggregation of rabbit and human platelets induced by adrenaline and 5-hydroxytryptamine by KB-R7943, a Na(+)/Ca(2+) exchange inhibitor.

    abstract::1. We investigated the effect of KB-R7943, a Na(+)/Ca(2+) exchange inhibitor, on the aggregation response induced by adrenaline and 5-hydroxytryptamine (5-HT), alone or in combination in human and rabbit platelets in the presence or absence of ouabain. 2. KB-R7943 inhibited aggregation induced by the combination of ad...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703928

    authors: Takano S,Kimura J,Ono T

    更新日期:2001-04-01 00:00:00

  • Sodium-calcium exchanger contributes to membrane hyperpolarization of intact endothelial cells from rat aorta during acetylcholine stimulation.

    abstract::1. The role of sodium-calcium exchanger in acetylcholine (Ach)-induced hyperpolarization of intact endothelial cells was studied in excised rat aorta. The membrane potential was recorded using perforated patch-clamp technique. 2. The mean resting potential of endothelial cells was -44.1+/-1.4 mV. A selective inhibitor...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705866

    authors: Bondarenko A

    更新日期:2004-09-01 00:00:00

  • Aconitine facilitates spontaneous transmitter release at rat ventromedial hypothalamic neurons.

    abstract::The effects of aconitine, an Aconitum alkaloid, on spontaneous inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs respectively) were investigated in the mechanically dissociated rat ventromedial hypothalamic (VMH) neurons in which native presynaptic nerve terminals remained intact. Under current-clamp co...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704517

    authors: Yamanaka H,Doi A,Ishibashi H,Akaike N

    更新日期:2002-02-01 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

  • Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases.

    abstract::Adrenomedullin (ADM) 2/intermedin (IMD) is a short peptide that belongs to the CGRP superfamily. Although it shares receptors with CGRP, ADM and amylin, ADM2 has significant and unique functions in the cardiovascular system. In the past decade, the cardiovascular effect of ADM2 has been carefully analysed. In this rev...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.13814

    authors: Zhang SY,Xu MJ,Wang X

    更新日期:2018-04-01 00:00:00

  • Investigation of the effects of platelet-activating factor (PAF) on ion transport and prostaglandin synthesis in human colonic mucosa in vitro.

    abstract::1 We have investigated the effects of platelet-activating factor (PAF), an endogenous mediator of inflammation, on ion transport and prostaglandin synthesis in the human isolated colon. 2 Application of PAF to the serosal surface of human colonic mucosa induced a marked, concentration-dependent increase in ion transpo...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701602

    authors: Borman RA,Jewell R,Hillier K

    更新日期:1998-01-01 00:00:00

  • Effect of endothelin antagonists, including the novel ET(A) receptor antagonist LBL 031, on endothelin-1 and lipopolysaccharide-induced microvascular leakage in rat airways.

    abstract::1. The effect of the novel ET(A) receptor antagonist LBL 031 and other selective and mixed endothelin receptor antagonists on endothelin-1 (ET-1)-induced and lipopolysaccharide (LPS)-induced microvascular leakage was assessed in rat airways. 2. Intravenously administered ET-1 (1 nmole kg(-1)) or LPS (30 mg kg(-1)) cau...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703691

    authors: Hele DJ,Birrell MA,Webber SE,Foster ML,Belvisi MG

    更新日期:2000-11-01 00:00:00

  • The gastric H,K-ATPase blocker lansoprazole is an inhibitor of chloride channels.

    abstract::1. It was postulated that swelling dependent chloride channels are involved in the proton secretion of parietal cells. Since omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are structurally related to phenol derivatives known to block swelling dependent chloride channels, we set out to test, w...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703070

    authors: Schmarda A,Dinkhauser P,Gschwentner M,Ritter M,Fürst J,Scandella E,Wöll E,Laich A,Rossmann H,Seidler U,Lang F,Paulmichl M

    更新日期:2000-02-01 00:00:00

  • Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L-dopa without modifying its cardiovascular effects.

    abstract::The potential of a new, potent, irreversible and selective inhibitor of monoamine oxidase type B, (E)-2-(3,4-dimethoxyphenyl)-3-fluorallyamine (MDL 72145), to augment the effects of L-DOPA in an animal model which reproduces the biochemical defect of Parkinson's disease has been evaluated. In rats bearing unilateral 6...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1986.tb10179.x

    authors: Fozard JR,Palfreyman MG,Robin M,Zreika M

    更新日期:1986-01-01 00:00:00

  • Some effects of PCO2 and pH on nerve tissue.

    abstract::1. Rat phrenic nerve preparations were used in vitro to study action potential amplitude and nerve conduction time under varying conditions of Pco(2) and sodium bicarbonate concentration in the surrounding Krebs solution.2. A correlation was found between action potential amplitude and pH but not between action potent...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1969.tb07980.x

    authors: Ellis FR

    更新日期:1969-01-01 00:00:00

  • nNOS-CAPON blockers produce anxiolytic effects by promoting synaptogenesis in chronic stress-induced animal models of anxiety.

    abstract:BACKGROUND AND PURPOSE:Anxiety disorder is a common mental health disorder. However, there are few safe and fast-acting anxiolytic drugs available that can treat anxiety disorder. We previously demonstrated that the interaction of neuronal NOS (nNOS) with its carboxy-terminal PDZ ligand (CAPON) is involved in regulatin...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.15084

    authors: Zhu LJ,Shi HJ,Chang L,Zhang CC,Si M,Li N,Zhu DY

    更新日期:2020-08-01 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

  • Beta-adrenoceptor subtype expression and function in rat white adipocytes.

    abstract::1. The pharmacological features of rat white adipocyte beta-adrenoceptor subtypes were investigated by saturation and beta-agonist competition studies with [3H]-CGP 12177 and by lipolysis induced by beta-agonists as well as their inhibition by CGP 20712A (selective beta 1-antagonist) and ICI 118551 (selective beta 2-a...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0700885

    authors: Germack R,Starzec AB,Vassy R,Perret GY

    更新日期:1997-01-01 00:00:00

  • Effects of chronic oral administration of the antidepressants, desmethylimipramine and zimelidine on rat cortical GABAB binding sites: a comparison with 5-HT2 binding site changes.

    abstract::1. The effects of chronic oral administration of desmethylimipramine (DMI) or zimelidine (1.25 and 5 mg kg-1 twice daily for 21 days) were studied on rat whole cortical gamma-aminobutyric acidB (GABAB) binding sites. No changes in receptor affinity or number were found with either drug. 2. A subsequent study of GABAB ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1988.tb11438.x

    authors: Cross JA,Horton RW

    更新日期:1988-02-01 00:00:00

  • Thromboxane (Tx) A2 receptor blockade and TxA2 synthase inhibition alone and in combination: comparison of anti-aggregatory efficacy in human platelets.

    abstract::1. The present study has compared the relative anti-aggregatory effect of various compounds which interfere with thromboxane (Tx) A2-dependent aggregation of human platelets in whole blood in vitro. These included the cyclo-oxygenase inhibitor aspirin, the TxA2 synthase inhibitor dazoxiben, the TxA2 (TP-) receptor blo...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1991.tb12200.x

    authors: Watts IS,Wharton KA,White BP,Lumley P

    更新日期:1991-02-01 00:00:00

  • Study of the effector mechanism involved in the production of haemorrhagic necrosis of the small intestine in rat passive anaphylaxis.

    abstract::1. The effector mechanism of intestinal necrosis in rat anaphylaxis was studied following several complementary approaches: (i) the use of monoclonal antibodies (mAb) belonging to different classes (IgG1, IgG2b and IgE anti-DNP), (ii) the assay of mediators, and (iii) the use of pharmacological tools. 2. Lethality and...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1994.tb13197.x

    authors: Pellón MI,Steil AA,Furió V,Sánchez Crespo M

    更新日期:1994-08-01 00:00:00

  • Alpha-4/beta-1 and alpha-L/beta-2 integrins mediate cytokine induced lung leukocyte-epithelial adhesion and injury.

    abstract:BACKGROUND AND PURPOSE:Injury to the alveolar epithelium is a critical feature of acute lung injury (ALI). Using a cytokine model of ALI we demonstrated previously that newly recruited mononuclear phagocytes (MNP) contributed to lung inflammation and injury. We hypothesized that cytokines delivered into the alveolar ai...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0707443

    authors: Parmley LA,Elkins ND,Fini MA,Liu YE,Repine JE,Wright RM

    更新日期:2007-11-01 00:00:00

  • Evaluation of ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, with a PGD2-responsive cell line from bovine embryonic trachea.

    abstract::ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, were evaluated with a fibroblastic cell line from bovine embryonic trachea (EBTr) which specifically responds to prostaglandin D2 (PGD2). ZK110841, equipotent to PGD2, elevated the adenosine 3':5'-cyclic monophosphate (...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1990.tb14645.x

    authors: Ito S,Okuda E,Sugama K,Negishi M,Hayaishi O

    更新日期:1990-01-01 00:00:00

  • Pharmacokinetic optimization of four soluble epoxide hydrolase inhibitors for use in a murine model of inflammation.

    abstract:BACKGROUND AND PURPOSE:Early soluble epoxide hydrolase inhibitors (sEHIs) such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) are effective anti-hypertensive and anti-inflammatory agents in various animal models. However, their poor metabolic stability and limited water solubility make them difficult to use pha...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2008.00009.x

    authors: Liu JY,Tsai HJ,Hwang SH,Jones PD,Morisseau C,Hammock BD

    更新日期:2009-01-01 00:00:00

  • Alpha 2-adrenoceptor blocking profile of SK&F 104078: further evidence for receptor subtypes.

    abstract::1. The ability of the putative, selective post-junctional alpha 2-adrenoceptor antagonist, SK&F 104078 to antagonize the effects of structurally-diverse agonists at pre-junctional alpha 2-adrenoceptors in the guinea-pig ileum and rat vas deferens in vitro and in the rat heart in vivo, and at post-junctional alpha 2-ad...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1991.tb12281.x

    authors: Akers I,Coates J,Drew GM,Sullivan AT

    更新日期:1991-04-01 00:00:00

  • Regulatory effect of sulphatides on BKCa channels.

    abstract:BACKGROUND AND PURPOSE:Sulphatides are sulphated glycosphingolipids expressed on the surface of many cell types, particularly neurones. Changes in sulphatide species or content have been associated with epilepsy and Alzheimer's disease. As the large conductance, calcium sensitive K(+) channel (BK(Ca)) are modulated by ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706947

    authors: Chi S,Qi Z

    更新日期:2006-12-01 00:00:00