Abstract:
:The concentration-dependence of the negative and positive inotropic effect of choline esters and of oxotremorine was studied in isometrically contracting papillary muscles of the guinea-pig. The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (IBMX, 100 mumol l-1), choline esters and oxotremorine produced concentration-dependent negative inotropic effects. Oxotremorine exhibited the highest negative inotropic potency (with a half-maximal effective concentration, EC50, of 20 nmol l-1) followed by carbachol (139 nmol l-1), methacholine (490 nmol l-1), acetylcholine in the presence of 10 mumol l-1 physostigmine (1.36 mumol l-1) and bethanechol (10 mumol l-1). Atropine was a competitive antagonist of the negative inotropic effects. Carbachol and oxotremorine decreased Vmax, overshoot and duration of slow Ca2+-dependent action potentials which had been elicited in the presence of 100 mumol l-1 IBMX. Choline esters produced a concentration-dependent positive inotropic effect. With an EC50 of 32 mumol l-1, carbachol was the most potent compound, followed by methacholine (35 mumol l-1), acetylcholine in the presence of 10 mumol l-1 physostigmine (46 mumol l-1) and bethanechol (142 mumol l-1). Compared to carbachol and methacholine which increased force by 100% of control, the increase induced by acetylcholine and bethanechol was only 64 and 58%, respectively. Atropine shifted the concentration-effect curves of all choline esters to higher concentrations. Choline esters caused intracellular Na+ activity to increase in the quiescent papillary muscle. This effect was reversed by atropine. Oxotremorine produced a small concentration-dependent positive inotropic effect (about 30% of the maximal effect of carbachol) which was resistant to atropine. Oxotremorine was a potent inhibitor of the positive inotropic effect of choline esters, and did not cause an increase in intracellular Na+ activity in the quiescent papillary muscle. The results show that muscarinic receptors of the ventricular myocardium mediate two inotropic effects, which are opposite in direction and differ in their concentration-dependence by a factor of 100. Although agonists differentiate between both inotropic effects, it is unknown whether the receptors involved represent receptor states or separate receptor subpopulations. The negative inotropic effect of choline esters and of oxotremorine can be best explained by adenylate cyclase inhibition. While stimulation of phosphoinositide hydrolysis might have been responsible for the positive inotropic effect of choline esters via modulation of cation-fluxes across the cell membrane, such a mechanism was not involved in the positive inotropic effect of oxotremorine.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Korth M,Kühlkamp Vdoi
10.1111/j.1476-5381.1987.tb16827.xsubject
Has Abstractpub_date
1987-01-01 00:00:00pages
81-90issue
1eissn
0007-1188issn
1476-5381journal_volume
90pub_type
杂志文章abstract::Oestrogens are important sex hormones central to health and disease in both genders that have protective effects on the cardiovascular and metabolic systems. These hormones act in complex ways via both genomic and non-genomic mechanisms. The genomic mechanisms are relatively well characterized, whereas the non-genomic...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01235.x
更新日期:2011-07-01 00:00:00
abstract::1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein exudation and microvascular permeability induced by topical, i.e. applied onto the tracheal mucosal surface, bradykinin (10 nmol; 20 microM, 5 min, 0.1 ml min-1) were studied in a perfused segment of trachea prepared in situ in anaesthetize...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16374.x
更新日期:1995-09-01 00:00:00
abstract::Intracellular potentials were recorded from rabbit atria, cardiac Purkinje cells and papillary muscles before and after exposure to various concentrations of indecainide. The effects of aprindine also were studied in the atrial preparations. Both drugs depressed the maximum rate of depolarization (MRD) in a dose-relat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08825.x
更新日期:1985-05-01 00:00:00
abstract::1. Transcriptional control of the human beta(2) adrenergic receptor gene (ADRB2) predominantly resides within a 549 base pair region immediately 5' to the start of translation. Within this region, four naturally occurring polymorphisms, -468 C-->G, -367 T-->C, -47 T-->C, and -20 T-->C, have been identified. 2. To dete...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704935
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The electromechanical window (EMW), the interval between the end of the T-wave and the end of the left ventricular pressure (LVP) curve, has recently been proposed as a predictor of risk of Torsade de Pointes (TdP) in healthy animals, whereby a negative EMW (mechanical relaxation earlier than rep...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12483
更新日期:2014-02-01 00:00:00
abstract::1. The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea-pig trachea. 2. In the presence of indomethacin (3 microM) and propranolol (1 microM) two contractile phases were evident in both t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14174.x
更新日期:1990-12-01 00:00:00
abstract::Diabetes mellitus belongs to the most rapidly increasing diseases worldwide. Approximately 90-95% of these patients suffer from type 2 diabetes mellitus, which is characterized by peripheral insulin resistance and the progressive loss of beta-cell function and mass. Considering the complications of this chronic diseas...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12624
更新日期:2014-06-01 00:00:00
abstract::1. The ionic dependence of [(3)H]-metaraminol transport by rabbit ventricular slices was studied.2. Transport was Na(+) dependent. Choline, Li(+), K(+), Rb(+) or Cs(+) could not be substituted for Na(+).3. Transport was K(+) dependent. Rb(+) and Cs(+), but not Li, could be substituted for K(+), their relative potencie...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb09936.x
更新日期:1971-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) metabolizes compounds containing catechol structures and has two forms: soluble (S-COMT) and membrane-bound (MB-COMT). Here we report the generation of a mouse line that expresses MB-COMT but not S-COMT. We compared the effects of deleting S-COMT only or both C...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00494.x
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Fibrosis, a pathological accumulation of collagen in tissues, represents a major global disease burden. Effective characterization of potential antifibrotic drugs has been constrained by poor formation of the extracellular matrix in vitro, due to tardy procollagen processing by collagen C-protein...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00387.x
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Dexpramipexole, a drug recently tested in patients with amyotrophic lateral sclerosis (ALS,) is able to bind F1Fo ATP synthase and increase mitochondrial ATP production. Here, we have investigated its effects on experimental ischaemic brain injury. EXPERIMENTAL APPROACH:The effects of dexpramipe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13790
更新日期:2018-01-01 00:00:00
abstract::1. In order to investigate the modulatory effects of adenosine on excitatory amino acid projections onto striatal medium spiny neurons, whole-cell patch clamp experiments were carried out in rat brain slices. The effects of various agonists for P1 (adenosine) and P2 (ATP) purinoceptors and their antagonists were inves...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701347
更新日期:1997-09-01 00:00:00
abstract::1. In anaesthetized patients under controlled respiration, samples of lumbar cerebrospinal fluid were withdrawn 15 and 60 min after an intravenous injection of 30 mg tubocurarine. When tested on the frog rectus muscle preparation contracted by acetylcholine, they exerted curare-like activity which corresponded to betw...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08206.x
更新日期:1973-04-01 00:00:00
abstract::1. Recent studies have shown antagonists at the NK1 subtype of receptor for tachykinins are antiemetics and suggested that this may result from blockade of tachykinin-mediated synaptic transmission at a central site in the emetic reflex. 2. We have used intracellular recording in vitro to study the pharmacology of tac...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701482
更新日期:1997-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Quercetin is a natural polyphenolic flavonoid that displays anti-diabetic properties in vivo. Its mechanism of action on insulin-secreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentrat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12194
更新日期:2013-07-01 00:00:00
abstract::1. We have previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31), without any further degradation products. In this study, we investigated the effect of synthetic ET-1 (1-31) on the proliferation of cultured human coronary artery smooth muscle c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702141
更新日期:1998-11-01 00:00:00
abstract::1 The effects of the prostaglandin synthetase inhibitor, indomethacin and the prostaglandin antagonist SC-19220 (1-acetyl-2-[8-chloro-10,11-dihydrodibenz (b,f) (1,4)oxazepine-10-carbonyl] hydrazine), were examined on the tone of the guinea-pig isolated tracheal preparation and on the responses of the preparation to pr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09724.x
更新日期:1974-12-01 00:00:00
abstract::1. We studied the effects of flash photolysis on the novel enantiomeric cardiac inotropes EMD 57033 (a calcium sensitizer) and EMD 57439 (a phosphodiesterase III inhibitor) in rat isolated ventricular trabeculae. 2. In skinned trabeculae, EMD 57439 had no effect on force production, consistent with lack of an active c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15641.x
更新日期:1996-08-01 00:00:00
abstract::1 The effect of methylene, thio, and imido substituted analogues of adenosine 5'-triphosphate (ATP) on surfactant phospholipid secretion and calcium mobilization in rat isolated alveolar Type II cells was studied. 2 ATP was the most potent secretagogue of adenine nucleotides studied. The rank order of agonist potency ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11282.x
更新日期:1987-08-01 00:00:00
abstract::1 Groups of mice were pretreated with the 5-hydroxytryptamine (5-HT) depletors, fenfluramine or p-chlorophenylalanine (PCPA), followed by pethidine or morphine. 2 Fenfluramine alone produced a short lasting analgesia but PCPA was without any effect. 3 Pethidine and morphine both increased hot plate reaction times meas...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09177.x
更新日期:1982-04-01 00:00:00
abstract::1. Effects of an orally active non-peptide (BK) B2 receptor antagonist, FR173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinoli nyl) oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide) on the plasma exudation in rat carrageenin-induced pleurisy were investigated. 2. Plasma exudation in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701194
更新日期:1997-06-01 00:00:00
abstract::1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivale...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12404.x
更新日期:1991-09-01 00:00:00
abstract::1. I.C.I. 50172 had marked quinidine-like effects on intracellular cardiac action potentials at concentrations above 20 mg/l. (6.61 x 10(-5)M). The rate of rise and overshoot of the action potential, conduction velocity and contractions were decreased. (-)-Propranolol had similar effects at less than 1/30 this concent...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb10576.x
更新日期:1969-10-01 00:00:00
abstract::I.c.v. self-administration of MDMA (0.01-2 micro g per infusion), alone and in combination with CP 55,940 (0.4 micro g infusion(-1)), was studied on an operant responding procedure. On the basis of individual preference for one of two levers, developed during training, rats were allowed to self-administer vehicle from...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704825
更新日期:2002-08-01 00:00:00
abstract::1. Experiments were performed in anaesthetized rabbits to examine the effects of calcitonin gene-related peptide (CGRP) and the CGRP antagonist CGRP8-37 on blood flow to the medial collateral ligament of the knee joint. 2. Topical application of CGRP (10(-13) to 10(-9) mol) to the exposed external surface of eight kne...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701265
更新日期:1997-08-01 00:00:00
abstract::1. Leptin, a pleiotropic hormone believed to regulate body weight, has recently been associated with inflammatory states and immune activity. Here we have studied the effect of leptin on expression of IFN-gamma-induced nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2), both prominent markers of macrophage act...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704903
更新日期:2002-11-01 00:00:00
abstract::The concentrations of catecholamines and the activities of dopamine-beta-hydroxylase were measured in blood obtained from decapitated diabetic and aged-matched control rats. The activity of dopamine-beta-hydroxylase in blood from diabetic rats was much greater (5 fold) than that seen for control rats. For both diabeti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08632.x
更新日期:1978-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Treatment with selective oestrogen receptor modulators (SERMs) reduces low-density lipoprotein (LDL) cholesterol levels. We assessed the effect of tamoxifen, raloxifene and toremifene and their combinations with lovastatin on LDL receptor activity in lymphocytes from normolipidaemic and familial ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13016
更新日期:2015-03-01 00:00:00
abstract::Vasoactive intestinal peptide (VIP) caused concentration-dependent relaxation in precontracted segments of trachea, hilar bronchus, intrapulmonary bronchus and intrapulmonary artery (IPA) isolated from cat lungs. VIP-induced relaxation responses were abolished by preincubation of tissues with the proteolytic enzyme, a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10766.x
更新日期:1984-06-01 00:00:00
abstract::1. The fall in arterial blood pressure with bradycardia that occurs on injection of clonidine into the cerebral ventricles and into the cisterna magna is attributed to an action on ;chemosensitive zones' situated at the ventral surface of the brain stem. This conclusion is based on the following results obtained in ca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08532.x
更新日期:1973-12-01 00:00:00