Abstract:
:In cardiac muscle cells both T-and L-type Ca(2+) channels (TTCCs and LTCCs, respectively) are expressed, and the latter are relevant to a process known as excitation-contraction coupling (ECC). Evidence obtained from docking studies suggests that isoindolines derived from α-amino acids bind to the LTCC CaV1.2. In the present study, we investigated whether methyl (S)-2-(1,3-dihydroisoindol-2-yl)-4-methylpentanoate (MDIMP), which is derived from L-leucine, modulates both Ca(2+) channels and ECC. To this end, mechanical properties, as well as Ca(2+) transients and currents, were all investigated in isolated cardiac myocytes. The effects of MDIMP on CaV1.2 (transiently expressed in 293T/17 cells) were also studied. In this system, evidence was found for an inhibitory action that develops and recovers in min, with an IC50 of 450µM. With respect to myocytes: atrial-TTCCs, atrial-LTCCs, and ventricular-LTCCs were also inhibited, in that order of potency. Accordingly, Ca(2+) transients, contractions, and window currents of LTCCs were all reduced more strongly in atrial cells. Interestingly, while the modulation of LTCCs was state-independent in these cells, it was state-dependent, and dual, on the ventricular ones. Furthermore, practically all of the ventricular LTCCs were closed at resting membrane potentials. This could explain their resistance to MDIMP, as they were affected in only open or inactivated states. All these features in turn explain the preferential down-regulation of the atrial ECC. Thus, our results support the view that isoindolines bind to Ca(2+) channels, improve our knowledge of the corresponding structure-function relationship, and may be relevant for conditions where decreased atrial activity is desired.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Santamaria-Herrera MA,Ríos-Pérez EB,de la Rosa JA,García-Castañeda M,Osornio-Garduño DS,Ramos-Mondragón R,Mancilla-Percino T,Avila Gdoi
10.1016/j.ejphar.2016.04.027subject
Has Abstractpub_date
2016-06-15 00:00:00pages
218-28eissn
0014-2999issn
1879-0712pii
S0014-2999(16)30242-4journal_volume
781pub_type
杂志文章abstract::Clonidine reduced cardiac acceleration induced by low frequency electrical stimulation of cardiac sympathetic nerve fibers in anesthetized and vagotomized dogs. This effect of clonidine was abolished by short periods of high frequency electrical stimulation. The inhibitory effect of clonidine was observed with 10- as ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90191-1
更新日期:1977-03-07 00:00:00
abstract::Perhexiline, a "metabolic" anti-anginal agent currently under investigation in management of congestive heart failure and acute coronary syndromes improves platelet nitric oxide responsiveness in patients with impaired responsiveness. The current study investigated possible interactions between perhexiline and the nit...
journal_title:European journal of pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ejphar.2007.01.001
更新日期:2007-03-29 00:00:00
abstract::We examined the effects of mammalian tachykinins on human bronchial secretion in vitro using fucose as an endogenous marker for mucus. Substance P (SP, 10(-9)-10(-5) M) increased secretion in a dose-related manner and was more potent than neurokinin A or neurokinin B. The enkephalinase (endopeptidase 24.11) inhibitor ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90322-1
更新日期:1989-12-19 00:00:00
abstract::This paper examines the biochemical and behaviour changes induced by an acute stress (five 10-s, 1-mA foot-shocks) in three groups of rats: (1) never stressed, (2) subjected to chronic variate stress for 20 days, (3) subjected to the same chronic stress and treated with 5 mg/kg per day amitriptyline. After 15 min, acu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00172-h
更新日期:1995-06-23 00:00:00
abstract::The experiments concerned the effect of ethacrynic acid (0.5 mM) on the adenosine triphosphate (ATP) content of rat mast cells and the effect on histamine release induced by the ionophore A23187 (10 microM). Ethacrynic acid decreased the ATP level of the cells in presence of antimycin A and glucose as well as in prese...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90285-6
更新日期:1983-09-02 00:00:00
abstract::The effects of beta-chlornaltrexamine (CNA, 5 mg/kg s.c.) on social conflict analgesia and brain opioid binding were investigated in mice at different times after the administration of the alkylating antagonist. The specific binding of [3H]etorphine to high-affinity binding sites and the stress-induced analgesia of at...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90525-0
更新日期:1988-10-18 00:00:00
abstract::The inhibitory effect of forskolin-stimulated 3',5'-cyclic monophosphate (c-AMP) synthesis in isolated rat adipocytes has been measured for eight typical adenosine receptor agonists. The percent inhibition was evaluated using concentrations of each compound corresponding to 100 times their Ki, inhibitory binding const...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(94)90224-0
更新日期:1994-03-15 00:00:00
abstract::The effects of acute or repeated treatment of male albino BKW mice with caerulein, a cholecystokinin octapeptide (CCK-8) agonist, and with devazepide (MK-329) and L-365,260, antagonists at CCKA ('peripheral') and CCKB ('central') receptors respectively, on motor activity and [propionyl-3H]propionylated-CCK-8 ([3H]pCCK...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90283-v
更新日期:1991-09-24 00:00:00
abstract::By far the most attention has been paid to the deleterious actions of nonsteroidal anti-inflammatory drugs (NSAIDs), including isoform selective agents that inhibit cyclooxygenase (COX), on the upper gastrointestinal tract, particularly the gastric and duodenal mucosa. However, recent studies confirm a relatively high...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2004.07.042
更新日期:2004-10-01 00:00:00
abstract::Denudatin B is an antiplatelet agent isolated from the flower buds of Magnolia fargesii. We studied the effects of denudatin B on the vasoconstriction of rat thoracic aorta induced by high potassium (K+) solution, norepinephrine (NE) and caffeine, and to elucidate its mode of action. The contraction of rat aorta cause...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90338-7
更新日期:1990-10-02 00:00:00
abstract::Clonidine and methysergide constrict the rabbit auricular artery by activating smooth muscle alpha-adrenoceptors. Clonidine inhibits and methysergide enhances responses to stimulation of the sympathetic nerves. Both drugs sensitise the artery to a variety of vasoconstrictor stimuli, although not to potassium chloride....
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90264-8
更新日期:1976-03-01 00:00:00
abstract::This study evaluated the coronary dopamine receptors by using the dopamine D1 receptor agonist fenoldopam, dopamine D2 receptor agonist propylbutyldopamine, and their selective antagonists SCH23390 and domperidone. Left circumflex coronary flow (CF), coronary perfusion pressure at constant flow, left ventricular hemod...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94126-i
更新日期:1990-11-06 00:00:00
abstract::An antagonist of morphine analgesia, N-cyclopropylmethylnorazidomorphine (CAM) inhibited the"wet shakes" appearing during spontaneous or nalorphine-precipitated morphine abstinence. CAM inhibited the pinna reflex more strongly than did morphine and selectively antagonized quipazine-induced head twitches; its inhibitio...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(78)90358-8
更新日期:1978-08-01 00:00:00
abstract::Proliferation and migration of vascular smooth muscle cells (VSMCs) play crucial roles in the development of vascular restenosis. Our previous study showed that CCN4, namely Wnt1 inducible signaling pathway protein 1 (WISP1), significantly promotes proliferation and migration of rat VSMCs, but its mechanism remains un...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.06.027
更新日期:2016-10-05 00:00:00
abstract::After prolonged stimulation, the delta-opioid receptor becomes desensitized by regulatory mechanisms such as receptor phosphorylation, internalization and down-regulation. In this study, we demonstrate that morphine treatment causes phosphorylation of S363 in the C-terminus of the human delta-opioid receptor. Morphine...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.07.024
更新日期:2005-09-20 00:00:00
abstract::This study was undertaken to define some of the cellular mechanisms of action of serotonin on cerebral vascular muscle. Application of serotonin to cat basilar artery resulted in a dose dependent depolarization and contraction beginning at 10(-8) M. The correlation coefficient relating the degree of force development ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90034-1
更新日期:1983-09-16 00:00:00
abstract::The effect of cytokines on the induction of contractile endothelin ET(B) receptors during organ culture was examined. Ring segments of rat superior mesenteric artery were used fresh or incubated for 24 h in Dulbecco's modified Eagle's medium alone, or with either interleukin-1beta, tumor necrosis factor-alpha (TNF-alp...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00381-7
更新日期:1999-07-09 00:00:00
abstract::The evidence suggests that stimulation of brain noradrenergic neurons plays an inhibitory role in rat mouse-killing (muricidal) aggression. Anxiolytic benzodiazepines inhibit locus coeruleus activity and previous data showed that chlordiazepoxide was capable of antagonizing the locus coeruleus-mediated suppression of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90625-3
更新日期:1984-10-15 00:00:00
abstract::The actions of tumor-promoting phorbol esters in smooth muscle excitation-contraction coupling were studied in isolated guinea pig ileum in the presence of various contractile agents. Muscarinic agonists, histamine and bradykinin elicited an initial transient phasic contraction and a subsequent sustained tonic contrac...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90348-t
更新日期:1991-08-29 00:00:00
abstract::Eleutheroside E (EE), a principal component of Eleutherococcus senticosus, has been reported to have anti-inflammatory and protective effects in ischemia heart etc. However, whether it can mitigate behavioral alterations induced by sleep deprivation, has not yet been elucidated. Numerous studies have demonstrated that...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.02.036
更新日期:2011-05-11 00:00:00
abstract::We have characterized the rat prostanoid EP1, EP2, EP3alpha and EP4 receptor subtypes cloned from spleen, hepatocyte and/or kidney cDNA libraries. Comparison of the deduced amino acid sequences of the rat EP receptors with their respective homologues from mouse and human showed 91% to 98% and 82% to 89% identity, resp...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01383-6
更新日期:1997-12-11 00:00:00
abstract::The in vitro biological effect of various opiates was studied in the guinea pig ileum bioassay. Besides their direct, immediate effect, certain opiates induced sensitivity changes which persisted after their removal and the complete recovery of the preparation. These specific, asymmetrical interactions may represent l...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(80)90488-4
更新日期:1980-03-07 00:00:00
abstract::A study was undertaken to ascertain why in the mouse vas deferens excitatory junction potentials facilitate whereas contractions depress during low frequency stimulation. In a set of contraction studies, where a conditioning stimulus was followed 2 s later by a test stimulus, depression in the first phase of contracti...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90295-x
更新日期:1994-08-11 00:00:00
abstract::Atropine-induced locomotor stimulation was investigated in the developing rat pretreated with 6-hydroxydopa at birth. The locomotor stimulation by atropine was first observed on day 20 and gradually increased with age. The treatment with 6-hydroxydopa potentiated atropine-induced locomotor stimulation on days later th...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(78)90149-8
更新日期:1978-08-15 00:00:00
abstract::The effects of electroconvulsive stimuli on the expression of mRNAs coding for preprotachykinin-A and the substance P-sensitive tachykinin NK1 receptor were examined in subregions of the rat striatum. In the electroconvulsive stimuli-treated animals, a 43% decrease in preprotachykinin-A mRNA was detected in the dorso-...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(96)00861-8
更新日期:1997-01-29 00:00:00
abstract::Stearoyl-CoA Desaturase 1 (SCD1) is a central enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. SCD1 is an emerging target in obesity and insulin resistance due to the improved metabolic profile obtained when the enzyme is genetically inactivated. Here, we have investiga...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.07.004
更新日期:2009-09-15 00:00:00
abstract::Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medical use. Piperine exhibits anti-inflammatory activity; however, the underlying mechanism remains unknown. We examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory response...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.05.026
更新日期:2010-09-10 00:00:00
abstract::In the search for a selective delta-opioid receptor agonist, (-)-(1R,5R,9R)-5,9-dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride ((-)-NIH 11082) and the (+)-enantiomer were synthesized and tested. (-)-NIH 11082 displayed antinociceptive activity in the paraphenylquinone test (PPQ test) in male ICR...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.03.008
更新日期:2007-07-02 00:00:00
abstract::The effect of nimodipine was studied on EEG power density spectra as well as on 31P-NMR spectra of the brain before, during and after four-vessel occlusion (FVO) in the restrained conscious rat. EEG-spectral analysis: eight rats were submitted to 5 min FVO and four of them received nimodipine (1 mg/kg orally) 75 min b...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90799-5
更新日期:1986-06-24 00:00:00
abstract::This study examined whether a clinically relevant concentration of the volatile anaesthetic halothane modifies the endothelium-dependent relaxation produced by acetylcholine (3 nM-10 microM), histamine (1 pM-0.1 microM) and anti-human immunoglobulin E (1:1000) in human isolated pulmonary arteries submaximally precontr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)85412-x
更新日期:1997-05-20 00:00:00