Abstract：
:The role of mobilization of intracellular Ca2+ in the adrenergic-stimulated cAMP accumulation in rat pinealocytes was investigated with thapsigargin, an agent that inhibits endoplasmic reticulum Ca2+-ATPase. It was found that although thapsigargin alone had no effect on the basal cAMP accumulation, it potentiated the beta-adrenergic-stimulated cAMP response by isoproterenol in a dose-dependent manner. The potentiation was abolished with ethylene glycol bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid-acetoxymethyl ester (EGTA-AM) but persisted in the presence of isobutylmethylxanthine, indicating that thapsigargin enhances cAMP synthesis through elevation of cytosolic intracellular Ca2+ concentration ([Ca2+]i). However, when the pinealocytes were stimulated by norepinephrine, a mixed alpha 1- and beta-adrenergic agonist, thapsigargin dose-dependently inhibited the cAMP response. To investigate this inhibitory effect of thapsigargin, we substituted ionomycin, a [Ca2+]i-elevating agent, and 4 beta-phorbol-12-myristate 13-acetate, an activator of protein kinase C, for the alpha(1)-adrenergic component of the norepinephrine-stimulated response. Although thapsigargin had no effect on the potentiation of the isoproterenol-stimulated cAMP accumulation by ionomycin, it significantly inhibited the potentiation by 4 beta-phorbol-12-myristate 13-acetate. Furthermore, the inhibitory effect of thapsigargin was not affected by cotreatment with EGTA-AM or ionomycin, suggesting that this effect is independent of [Ca2+]i. Similar results were obtained when cyclopiazonic acid was used to inhibit the Ca(2+)-ATPase. Taken together, our results indicate that thapsigargin enhances the beta-adrenergic-stimulated cAMP accumulation through its action in elevating [Ca2+]i but inhibits the potentiation of the beta-adrenergic-stimulated cAMP response by protein kinase C, as a consequence of Ca(2+)-ATPase inhibition.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Ho AK,Ogiwara T,Chik CLsubject
Has Abstractpub_date
1996-06-01 00:00:00pages
1104-12issue
6eissn
0026-895Xissn
1521-0111journal_volume
49pub_type
杂志文章abstract：:The highly conserved aspartate residue in the second transmembrane domain of G protein-coupled receptors is present in position 113 in the type 1 neurotensin receptor (NTR1) but is replaced by an Ala residue in position 79 in the type 2 neurotensin receptor (NTR2). NTR1 couples to Galphaq to stimulate phospholipase C ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.55.2.210
更新日期：1999-02-01 00:00:00
abstract：:Although the thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well established agents for the treatment of leukemia, controversies remain regarding their main mode of action. Previous evidence has suggested that although 6-TG exerts a cytotoxic effect through incorporation of 6-thioguanine nucleot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.1.102
更新日期：2002-07-01 00:00:00
abstract：:Bordetella pertussis, the pathogen responsible for whooping cough, releases a soluble calmodulin-sensitive adenylate cyclase into its culture medium which enters several different types of animal cells and elevates intracellular cAMP. In this study, the influence of B. pertussis adenylate cyclase on intracellular cAMP...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-05-01 00:00:00
abstract：:Thapsigargin is a specific inhibitor of the sarco/endoplasmic reticulum Ca(2+) ATPase of the endoplasmic reticulum. Here, we show that stimulation of human HaCaT keratinocytes with nanomolar concentrations of thapsigargin triggers expression of activating transcription factor (ATF) 3, a basic-region leucin zipper tran...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.067637
更新日期：2010-11-01 00:00:00
abstract：:The involvement of mitogen-activated protein (MAP) kinases in the mitogenic effect of thyrotropin (TSH) is not fully elucidated. In FRTL-5 cells, we found that the MAP kinase kinase (MEK) inhibitors UO126 and PD98059 substantially decreased TSH-induced DNA synthesis, indicating that MAP kinases are involved in the TSH...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.5.924
更新日期：2001-11-01 00:00:00
abstract：:In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT of voltage-gated Ca2+ channels in human atrial myocytes and to chara...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：:Five separate guanine nucleotide-binding proteins (G proteins) were immunologically identified in membranes from neuroblastoma x glioma NG108-15 hybrid cells. These alpha subunit proteins were Gi2 alpha, two isoforms of Gi3 alpha, and two isoforms of Go alpha. The G proteins that interacted with delta-opioid receptors...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:We previously demonstrated that murine bone marrow stromal cells express high levels of cytochrome P4501B1 (CYP1B1) that metabolizes 7,12-dimethylbenza[a]anthracene (DMBA), and that DMBA activates the Ah receptor (AhR) in these cells in vitro. More recently, we reported that CYP1B1 is required for DMBA-induced lymphob...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.56.6.1317
更新日期：1999-12-01 00:00:00
abstract：:The gamma-aminobutyric acid(A) (GABA(A)) receptor contains a binding site (or sites) for benzodiazepines and related ligands. Previous studies have shown that the residue occupying position 101 (rat numbering) of the alpha subunit is particularly important in determining how some of these compounds interact with the r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:The subunit composition and pharmacological regulation of rat neuronal nicotinic cholinergic receptors were assessed. Specific immunoprecipitation was determined in solubilized rat brain homogenates using [3H]cytisine, a high affinity agonist at nicotinic receptors, in conjunction with polyclonal antisera generated ag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Modulation of neuronal ion channels by the cloned rat brain CB1 cannabinoid receptor was investigated with the use of a heterologous neuronal expression system. Transient expression of the rat brain CB1 cannabinoid receptor was accomplished through microinjection of in vitro transcribed cRNA into the cytoplasm of enzy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectabl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.040105
更新日期：2008-09-01 00:00:00
abstract：:Neuromedin U (NmU) is a 25 amino acid peptide prominently expressed in the upper gastrointestinal (GI) tract and central nervous system. It is highly conserved throughout evolution and induces smooth muscle contraction in a variety of species. Our understanding of NmU biology has been limited because the identity of i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.4.870
更新日期：2000-10-01 00:00:00
abstract：:Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is important for excretion of organic cations in the kidney and liver, where it is located on the luminal side. Although its functional and regulatory characteristics have been clarified, its pharmacokinetic roles in vivo have yet to be elucidated. In the present study, ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.056242
更新日期：2009-06-01 00:00:00
abstract：:Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation. We report here that in primary mouse keratinocytes PMA caused translocation of PKC-ep...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Poly(ADP-ribose) polymerase-1 (PARP-1) is a NAD-consuming enzyme with an emerging key role in epigenetic regulation of gene transcription. Although PARP-1 expression is characteristically restricted to the nucleus, a few studies report the mitochondrial localization of the enzyme and its ability to regulate organelle ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.070110
更新日期：2011-06-01 00:00:00
abstract：:Obesity is now recognized as a rapidly increasing worldwide threat to health, largely as a result of causing diabetes. Thus, considerable efforts are underway in the pharmaceutical industry to find drugs to treat this condition. Target validation in various academic and industrial laboratories has revealed a number of...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.106.026104
更新日期：2006-09-01 00:00:00
abstract：:Smooth muscle preparations of human aorta or pig coronary arteries contain nearly equal amounts of cGMP-dependent protein kinase isozymes (cGMP kinase I alpha and I beta). In order to understand the roles of these isozymes in relaxing vascular smooth muscle, several new cGMP analogs were synthesized and tested for pot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:In saturation studies with [3H]dihydromorphine, unlabeled D-Ala2-D-Leu5-enkephalin (1 nM) inhibited the high-affinity binding component far more potently than the lower-affinity one. Similarly, morphine (1 nM) inhibited the higher-affinity binding of 3H-D-Ala2-D-Leu5-enkephalin to a greater extent than its lower-affin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:The effects of saturating concentrations of DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and the pyrethroid insecticides cismethrin and deltamethrin on alkaloid-dependent activation of the voltage-sensitive sodium channel were studied using measurements of 22Na+ uptake into mouse brain synaptosomes. In survey e...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:Hepatic very-low-density lipoprotein particles (VLDL) containing full-length apolipoprotein B100 are metabolized in the blood stream to low-density lipoprotein (LDL) particles, whose elevated levels increase the risk of atherosclerosis. Statins and bile-acid sequestrants are effective LDL-lowering therapies for many p...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.2.269
更新日期：2002-02-01 00:00:00
abstract：:Inhibition of cannabinoid receptor 1 (CB1) has shown efficacy in reducing body weight and improving metabolic parameters, with the effects correlating with target engagement in the brain. The peripheral effects of inhibiting the CB1 receptor has been appreciated through studies in diet-induced obese and liver-specific...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.064980
更新日期：2010-09-01 00:00:00
abstract：:In vivo administration of the porphyrogenic agent allylisopropylacetamide (AIA) to phenobarbital-pretreated rats results in marked loss of hepatic cytochrome P-450 content. Using isozyme-selective functional markers, we now show that such loss reflects inactivation of several phenobarbital-inducible and constitutive i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:P-glycoprotein, an ATP-driven efflux pump, regulates permeability of the blood-brain barrier (BBB). Sphingolipids, endogenous to brain tissue, influence inflammatory responses and cell survival in vitro. Our laboratory has previously shown that sphingolipid signaling by sphingosine 1-phosphate decreases basal P-glycop...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107169
更新日期：2017-04-01 00:00:00
abstract：:The binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cardiac muscarinic receptors was inhibited not only by classical muscarinic antagonists but also by nicotinic blocking agents and inhibitors of acetylcholinesterase. Gallamine, pancuronium, ambenonium, and decamethonium were the most potent of these agents examin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
abstract：:The binding of [3H]Hspiroperidol to D2 dopaminergic receptors in rat striatum was compared to the binding of [3H]dopamine to its binding sites. Both radioligands labeled apparently homogeneous populations of high affinity, stereoselective, saturable sites, determined from analysis of saturation isotherms. [3H]Spiroper...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:Poly(A)+ RNA from mammalian retina expresses bicuculline/baclofen-insensitive gamma-aminobutyric acid (GABA) receptors in Xenopus oocytes with properties similar to those of homooligomeric GABA rho 1 receptors. The pharmacological profile of these rho-like receptors was extended by measuring sensitivities to various G...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:The effects of dimethyl sulfoxide (DMSO) on subsynaptic response and quantal release of transmitter have been studied at the mammalian neuromuscular junction. Subsynaptically, at low concentrations (up to 1% by volume), DMSO prolongs the time course of decay of miniature endplate currents, (MEPCs), with no significant...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
abstract：:Although much has been learned about the mechanisms of ligand selectivity between different opioid receptor subtypes, little is known about the common opioid binding pocket shared by all opioid receptors. The recently discovered orphanin system offers a good opportunity to study the mechanisms involved in the binding ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.4.772
更新日期：1998-04-01 00:00:00
abstract：:Mouse embryonic spinal cord neurons in culture exhibit spontaneous calcium oscillations from day in vitro (DIV) 6 through DIV 10. Such spontaneous activity in developing spinal cord contributes to maturation of synapses and development of pattern-generating circuits. Here we demonstrate that these calcium oscillations...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.071456
更新日期：2011-06-01 00:00:00
