Abstract：
:The carbonic anhydrase (CA) isozyme (IV) in microsomes is thought to have a dominant role in secretory processes. Using microsomes from bovine kidney and lung (which had the same activity), we have measured the Km and kcat for CO2 hydration and compared these numbers with those for CA I (red blood cells and gut), CA II (red blood cells and secretory cells), and CA III (muscle). For kidney CA IV, Km is 10 mM and kcat is 170,000 sec-1 at 0 degree, approaching the rate for CA II but much greater than those for CA I or III. The Ki values for 11 sulfonamides with CA IV were measured and in all cases showed less binding (averaging 17-fold) than to CA II. This is the result of reduction of the association rate constants (k(on)), whereas the dissociation constants of the drug-enzyme complexes (k(off) are similar between CA II and IV. Based on these data, full physiological effects may be expected when inhibition of CA IV is about 99%. Anion inhibition of CA IV is similar to that of CA II and less than that of CA I or CA III. Data are compatible with the proposed role of CA IV in physiological events, i.e., HCO3- formation and secretion at one cell border and H+ separation and excretion at the other.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Maren TH,Wynns GC,Wistrand PJsubject
Has Abstractpub_date
1993-10-01 00:00:00pages
901-5issue
4eissn
0026-895Xissn
1521-0111journal_volume
44pub_type
杂志文章abstract：:A family of five cholinergic muscarinic receptor genes (m1, m2, m3, m4, and m5) has recently been identified and cloned. In order to investigate the pharmacological properties of the individual muscarinic receptors, we have transfected each of these genes into Chinese hamster ovary cells (CHO-K1) and have established ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Monoamine oxidases (MAOs) A and B, flavin-containing enzymes found in the outer mitochondrial membrane, oxidize many important biogenic and xenobiotic amines. The two enzymes are expressed in many tissues, with some tissues containing primarily one form and others containing both. Although MAO in placental mitochondri...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:Adenosine acting via A2a receptors (A2aR) is a potent cerebral vasodilator that relaxes vascular smooth muscle cells (VSMCs) by a mechanism attributed to activation of cAMP-dependent protein kinase (cAK). We examined effects of adenosine and its mechanism of action on L-type Ca2+ channels in native VSMCs from rat basi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.3.640
更新日期：2003-09-01 00:00:00
abstract：:In standard 3H-opioid binding assays, the benzoylhydrazone derivative of naloxone (6-desoxy-6-benzoylhydrazido-N-allyl-14-hydroxydihydronormorphi none; NalBzoH) inhibited mu, kappa, and delta binding at nanomolar concentrations. At concentrations as low as 1 nM, it also produced a wash-resistant inhibition of opioid b...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:We recently reported the cloning of a novel alpha 1-adrenergic receptor (AR), the alpha 1CAR. By transient and stable expression of the alpha 1CAR and the previously cloned alpha 1BAR in COS-7 and HeLa cells, respectively, we have now compared their ability to interact with major signal-transduction pathways (includin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:A collection of analogues of atrial natriuretic peptide (ANP) were screened for their ability to inhibit ANP-induced cGMP stimulation. The antagonists revealed through this screen are structurally related; almost all are substituted at either aspartate-13 or phenylalanine-26. This tendency is consistent throughout sev...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:We reported previously that protein associated with Myc (PAM) interacts with the C2 domain of type V adenylyl cyclase (ACV-C2) and that purified PAM is a potent inhibitor of Galphas-stimulated ACV activity (J Biol Chem 276:47583-47589, 2001). The present study was conducted to identify the region in PAM that inhibits ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.005355
更新日期：2005-01-01 00:00:00
abstract：:This article describes the expected phenotypic behavior of all types of ligands in constitutively active receptor systems and, in particular, the molecular mechanisms of inverse agonism. The possible physiological relevance of inverse agonism also is discussed. Competitive antagonists with the molecular property of ne...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.65.1.2
更新日期：2004-01-01 00:00:00
abstract：:Telomerase activity is expressed in most types of cancer cells but not in normal somatic cells, suggesting that telomerase may be an important target for cancer chemotherapy. Inhibition of telomerase results in telomere erosion, leading to the subsequent growth arrest of cancer cells followed by senescence or cell dea...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.5.1117
更新日期：2003-05-01 00:00:00
abstract：:Isoproterenol increases and decreases contractile force at low and high concentrations, respectively, through beta(2)-adrenoceptors overexpressed in transgenic mouse heart (TG4), consistent with activation of both G(s) and G(i) proteins. Using TG4 hearts, we demonstrated that epinephrine behaves like isoproterenol, bu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.5.1313
更新日期：2004-05-01 00:00:00
abstract：:The present study characterizes the methanethiosulfonate (MTS) inhibition profiles of 26 consecutive cysteine-substituted mutants comprising transmembrane (TM) helix 6 of the human apical Na(+)-dependent bile acid transporter (SLC10A2). TM6 is linked exofacially to TM7 via extracellular loop 3. TM7 was identified prev...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.041640
更新日期：2008-02-01 00:00:00
abstract：:We reported earlier that delta 9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marihuana, increased markedly the level of unesterified arachidonic acid (AA) in guinea pig cerebral cortex slices prelabeled with [14C]AA. The purpose of the present study was to clarify the mechanism underlying THC-enhan...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:Freshly isolated rat hepatocytes rapidly lose their cytochrome P450 (P450) proteins and mRNAs, with no evidence of subsequent restoration, after placement into traditional systems of primary culture on type I collagen. We examined the patterns of expression of 10 constitutively expressed P450 mRNAs in rat hepatocytes ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:Interleukin-2 (IL-2) is an immunoregulatory cytokine whose biological effects are mediated through interaction with specific receptors on the surface of target cells. Due to its presumed role in generating a normal immune response, IL-2 is being evaluated for the treatment of a variety of tumors, in addition to infect...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Tumors provide an extremely abnormal microenvironment that stimulates neovascularization from surrounding vessels and causes altered gene expression within vascular cells. Up-regulation of vascular endothelial growth factor (VEGF) receptors has allowed selective destruction of tumor vessels by administration of a chim...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.015628
更新日期：2005-12-01 00:00:00
abstract：:The aim of this study was to clarify the mechanism by which cytochrome P450 (P450)-mediated catalytic activity is decreased following interferon (IFN) administration. Microsomal steroid hydroxylation was assessed to test the hypothesis that IFN selectively decreases the activities of individual P450 isozymes in male r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:We describe here the cloning and characterization of a rat homolog of the chemokine receptor CXCR3. The predicted amino acid sequence of rat CXCR3 contains 367 amino acid residues, sharing 96 and 87% amino acid sequence identity to the murine and human CXCR3, respectively. Among a large panel of chemokines tested, onl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:To learn more about the binding conformation of phencyclidine (PCP) and to arrive at analogues of higher affinity, which may serve as noncompetitive N-methyl-D-aspartate receptor antagonists, eight optically pure PCP analogues were designed with the aid of computer. These compounds represent conformationally constrain...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:In light of the potential use of the thiazolidinedione family of peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists in prostate cancer treatment, this study assessed the mechanism by which these agents suppress prostate-specific antigen (PSA) secretion in prostate cancer cells. Two lines of evidence...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.018333
更新日期：2006-05-01 00:00:00
abstract：:Vasopressin receptor subtype(s) responsible for stimulation of insulin release from pancreatic beta cells were investigated by using subtype-selective antagonists and mice that were genetically lacking either V1a or V1b receptors. Arginine vasopressin (AVP) increased insulin release from isolated mouse islet cells in ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.3.623
更新日期：2004-03-01 00:00:00
abstract：:Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subt...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.043505
更新日期：2008-04-01 00:00:00
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 ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:We describe the nucleic acid sequence encoding a human 5-hydroxytryptamine1D (5-HT1D) serotonin receptor and some of the functional characteristics of the gene product. The receptor gene was isolated by hybridization to a probe based on a canine thyroid cDNA (called RDC4) previously isolated by others and believed to ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Phosphorylation of tau protein promotes stability of the axonal cytoskeleton; aberrant tau phosphorylation is implicated in the biogenesis of paired helical filaments (PHF) seen in Alzheimer's disease. Protein kinases and phosphatases that modulate tau phosphorylation have been identified using in vitro techniques; ho...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:The sympathetic nervous system modulates cardiac contractility and rate by activating beta-adrenergic receptors (beta AR) expressed on cardiac myocytes and specialized cells in the sinoatrial node and the conduction system. Recent clinical studies have suggested that beta-adrenergic receptors also play a role in cardi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-09-01 00:00:00
abstract：:The CYP2C genes are extensively regulated at the transcriptional stage. The present study shows for the first time that CYP2Cs are also regulated post-transcriptionally by microRNAs (miRNAs). By using online search engines, we found potential miRNA response elements (MREs) in the 3'-untranslated region (3'-UTR) of the...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078386
更新日期：2012-09-01 00:00:00
abstract：:Carbachol is 100 times more potent for inhibiting cyclic AMP formation than for stimulating phosphoinositide (PI) hydrolysis in chick heart cells. To determine whether this reflects differences in agonist affinity of the receptor(s) coupled to the two responses, we measured these functional responses following removal...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
abstract：:Pregnanolone [5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha)] and allopregnanolone [5 alpha-pregnan-3 alpha-ol-20-one (5 alpha 3 alpha)] are neuroactive steroids that are reduced metabolites of progesterone. Both 5 beta 3 alpha and 5 alpha 3 alpha are potent positive modulators of the gamma-aminobutyric acid respon...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:Cannabinoids have been implicated in the reduction of glioma growth. The present study investigated a possible relationship between the recently shown induction of cyclooxygenase (COX)-2 expression by the endocannabinoid analog R(+)methanandamide [R(+)-MA] and its effect on the viability of H4 human neuroglioma cells....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.002618
更新日期：2004-12-01 00:00:00
abstract：:Vesnarinone, a cardiotonic agent, blocks I(Kr) and, unlike other I(Kr) blockers, produces a frequency-dependent prolongation of action potential duration (APD). To elucidate the mechanisms, we studied the effects of vesnarinone on HERG, the cloned human I(Kr) channel, heterologously expressed in Xenopus laevis oocytes...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.2.244
更新日期：2001-08-01 00:00:00
