Abstract:
:We have identified alpha 2-adrenergic receptors on human erythroleukemia (HEL) cells, a suspension-grown cell line related to human platelets. properties of receptors were assessed in intact cells by binding of the antagonist [3H]yohimbine and by inhibition of cAMP accumulation. [3H]Yohimbine labeled 5900 +/- 2100 receptors/cell with a Kd of 3.6 +/- 0.9 nM (n = 7). alpha 2-Adrenergic receptors were potently coupled to inhibition of adenylate cyclase, with EC50 values for epinephrine, UK-14,304, and p-aminoclonidine in the low nM range. Treatment of cells with pertussis toxin abolished this response. In radioligand binding studies with membrane preparations [3H]yohimbine and [3H]UK-14,304 bound to the same number of sites (71 versus 69 fmol/mg of protein), and epinephrine competed for [3H]yohimbine binding in a biphasic manner. After addition of GTP, no high affinity [3H]UK-14,304 binding was detected, and epinephrine competed for [3H]yohimbine binding with lower affinity at both 4 degrees and 37 degrees. In studies with intact cells, we detected no specific binding of [3H]UK-14,304 at either 37 degrees or 4 degrees. At 37 degrees, epinephrine competed for all [3H]yohimbine binding sites with a low apparent affinity (Ki = 21 microM), whereas at 4 degrees epinephrine (up to 1 mM) was able to compete for only 59 +/- 13% of [3H]yohimbine-binding sites. The potency of epinephrine in competing for [3H]yohimbine sites in intact cells at 4 degrees was greater than at 37 degrees (Ki = 1 microM) and was similar to that observed with membranes in the presence of GTP. We hypothesize that sites not detectable by epinephrine at 4 degrees are sequestered within the cell. Treatment of HEL cells with pertussis toxin reduced the proportion of receptors on the surface from 51 +/- 12% to 23 +/- 7% (n = 3, p less than 0.05) of the total sites. Treatment of HEL cells with epinephrine (100 microM, 1 hr) reduced the cell surface component to 25 +/- 8% (n = 3) of the total sites. This treatment was not accompanied by significant desensitization of the ability of epinephrine to inhibit cAMP accumulation. We conclude that alpha 2-adrenergic receptors exist in more than one compartment in HEL cells and that interaction of receptors with a guanine nucleotide-binding protein or with agonist may regulate this compartmentation. These cells provide a new model system for the study of expression and metabolism of alpha 2-adrenergic receptors.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
McKernan RM,Howard MJ,Motulsky HJ,Insel PAsubject
Has Abstractpub_date
1987-08-01 00:00:00pages
258-65issue
1eissn
0026-895Xissn
1521-0111journal_volume
32pub_type
杂志文章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
abstract::Selegiline, a selective monoamine oxidase type B inhibitor, is beneficial in the treatment of Parkinson's disease. However, this beneficial effect is only transient, and patients must ultimately resort to treatment with standard levodopa therapy. We studied the effects of chronic selegiline treatment on the rat nigros...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::Low-density lipoprotein (LDL) is known to be a mitogenic factor for vascular smooth muscle cells (VSMCs), fibroblasts, and endothelial cells. In the current study, we describe possible intracellular mechanisms by which LDL elicits its mitogenic effects. Stimulation of VSMCs with LDL resulted in a pertussis-toxin (PTX)...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.52.3.389
更新日期:1997-09-01 00:00:00
abstract::The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-K alpha (TsTX-K alpha) and Dendroaspis angusticeps (snake) toxin dendrotoxin (alpha-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated prev...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::The decrease in mu-opioid receptor activity after chronic agonist exposure (1 microM [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin) is largely due to kinase-mediated phosphorylation of intracellular receptor domains. We have recently shown that the substitution of two putative Ca(2+)/calmodulin-dependent protein kinase I...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.2.328
更新日期:2000-08-01 00:00:00
abstract::The observations from Dunlap and Fischbach that transmitter-mediated shortening of the duration of action potentials could be caused by a decrease in calcium conductance led to numerous studies of the mechanisms of modulation of voltage-dependent calcium channels. Calcium channels are well known targets for inhibition...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.104.002261
更新日期:2004-11-01 00:00:00
abstract::Ceramides are naturally occurring compounds recognized to mediate apoptosis. N-acylsphingosines, containing a double bond at carbons 4 and 5 of their sphingoid backbone, are thought to be the active form, because N-acylsphinganines with completely saturated sphingoid are inactive. In the present study, we synthesized ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.5.1249
更新日期:2001-05-01 00:00:00
abstract::The renal outer medullary potassium channel (ROMK) is expressed in the kidney tubule and critically regulates sodium and potassium balance. The physiological functions of other inward rectifying K(+) (Kir) channels expressed in the nephron, such as Kir7.1, are less well understood in part due to the lack of selective ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.059840
更新日期:2009-11-01 00:00:00
abstract::The pharmacological effects of angiotensin II (AII) are potently inhibited by several peptide and recently synthesized nonpeptide AII receptor antagonists. The interaction of sarcosine1, isoleucine8-AII (sarile), sarcosine1,O-methyltyrosine4-AII (sarmesin), and the nonpeptide AII antagonists 2-n-butyl-4-chloro-5- hydr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::A fusion protein consisting of the endothelin B (ET(B)) receptor and the enhanced green fluorescent protein (EGFP) in conjunction with Cyanin3- or fluorescein-conjugated endothelin 1 (Cy3-ET1, Fluo-ET1) was used to investigate the ligand-mediated internalization of the ET(B) receptor. The ET(B) receptor and the ET(B)/...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::The midbrain periaqueductal gray (PAG) is involved in organizing behavioral responses to threat, stress, and pain. These PAG functions are modulated by cholinergic agents. In the present study, we examined the cholinergic modulation of synaptic transmission in the PAG using whole-cell voltage-clamp recordings from rat...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.045872
更新日期:2008-11-01 00:00:00
abstract::Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyel...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.068122
更新日期:2011-04-01 00:00:00
abstract::Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin. In the present study, we investigated the role of the tPA-plasmin system in depolarization-evoked dopamine (DA) and acetylcholine (ACh) release in the nucleus accumbens (NAc) and hippocampus, respectively, of mic...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.022467
更新日期:2006-11-01 00:00:00
abstract::The effects of alpha 2-adrenergic receptors are usually attributed to inhibition of adenylyl cyclase through pertussis toxin-sensitive Gi coupling. In kidney distal convoluted tubule (DCT) cells, stimulation of Na+/K(+)-ATPase by alpha 2 receptors involves activation of protein kinase C (PKC). To identify the signal p...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::The expression and molecular regulation of the cytochrome P450IA (P450IA) gene subfamily have been examined in rat hepatic tissue after treatment with pyridine. The microsomal ethoxyresorufin O-deethylase activity, which has been shown to be specific for the P450IA subfamily, was increased approximately 2- and 3.5-fol...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-07-01 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
abstract::We have synthesized and characterized a high-affinity alpha 1-adrenergic receptor probe, 4-amino-6,7-dimethoxy-2[4'- [5"(3"'-125I-iodo-4"'-aminophenyl)pentanoyl]-1'-piperazinyl] quinazoline (125I-A55453). This ligand binds reversibly to rat hepatic plasma membranes with high affinity (KD = 77 +/- 6 pM), and it labels ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::The highly specialized metabotropic glutamate receptor type 6 (mGluR6) is postsynaptically localized and expressed only in the dendrites of ON bipolar cells. Upon activation of mGluR6 by glutamate released from photoreceptors, a nonselective cation channel is inhibited, causing these cells to hyperpolarize. Mutations ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.058628
更新日期:2009-11-01 00:00:00
abstract::Recent years have witnessed the discovery of novel selective agonists of the M(1) muscarinic acetylcholine (ACh) receptor (mAChR). One mechanism invoked to account for the selectivity of such agents is that they interact with allosteric sites. We investigated the molecular pharmacology of two such agonists, 1-[3-(4-bu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.064345
更新日期:2010-07-01 00:00:00
abstract::Microinjection, but not extracellular application, of cytidine-5'-diphosphate-D-glucose (CDPG) has been shown to elicit Ca(2+)-dependent currents in Xenopus laevis oocytes. These responses were comparable to those of inositol-1,4,5-trisphosphate (InsP3) in being both rapid and dose dependent. For example, maximal ampl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::We have identified four new mu-opiod receptor (MOR)-1 exons, indicating that the gene now contains at least nine exons spanning more than 200 kilobases. Replacement of exon 4 by combinations of the new exons yields three new receptors. When expressed in Chinese hamster ovary cells, all three variants displayed high af...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.56.2.396
更新日期:1999-08-01 00:00:00
abstract::Cell-penetrating peptides are amphipathic or cationic oligopeptides able to transport covalently attached cargoes across cell membranes. Peptide aptamers are polypeptide fragments of endogenous proteins that mimic and thus perturb interactions with other cellular proteins. Combining aptamer and CPP technology can gene...
journal_title:Molecular pharmacology
pub_type: 评论,杂志文章
doi:10.1124/mol.105.011429
更新日期:2005-04-01 00:00:00
abstract::Leukotriene B4 (LTB4) induced rapid breakdown of prelabeled inositol phospholipids in rat peritoneal polymorphonuclear leukocytes (PMNs). Formation of [3H]inositol triphosphate ([3H]IP3) was rapid, with a peak of 250-300% of the control level, after 5-15 sec of exposure to LTB4. Accumulation of [3H]inositol bisphospha...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::The effect of relatively nontoxic levels of HgCl2 on semiconservative DNA synthesis and on DNA repair induced following treatment of intact cells with X-ray or ultraviolet (UV) light has been studied in cultured Chinese hamster ovary cells. In the presence of 1 microM HgCl2 the repair of DNA strand breaks induced by 4...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract::alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are recognized as the principal nicotine binding site in brain. Recombinant alpha4beta2 nAChR demonstrate biphasic concentration-response relationships with low- and high-EC50 components. This study shows that untranslated regions (UTR) can influence expression of...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.020198
更新日期:2006-07-01 00:00:00
abstract::In Rat-1 fibroblasts, endothelin-1 and a protein kinase C-stimulating phorbol ester stimulated extracellular signal-regulated kinase (ERK), whereas phenylephrine, acting at stably transfected human alpha1A-adrenoceptors, inhibited basal and endothelin-1- and phorbol ester-stimulated ERK. On the other hand, phenylephri...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.54.5.755
更新日期:1998-11-01 00:00:00
abstract::The interaction of hormones acting via the mobilization of calcium and stimulation of cAMP levels in cells was examined by determining the effects of carbachol and forskolin on cAMP and cGMP accumulation in mouse parotid gland. Treatment of isolated acini with either carbachol (0.01 to 20 microM) or forskolin (1 micro...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::The microtubule-binding taxanes, docetaxel and cabazitaxel, are administered intravenously for the treatment of castration-resistant prostate cancer (CRPC) as the oral administration of these drugs is largely hampered by their low and highly variable bioavailabilities. Using a simple, rapid, and environmentally friend...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.118539
更新日期:2020-06-01 00:00:00
abstract::The cytochrome P450 26 family is believed to be responsible for all-trans-retinoic acid (atRA) metabolism and elimination in the human fetus and adults. CYP26A1 and CYP26B1 mRNA is expressed in a tissue-specific manner, and mice in which the CPY26 isoform has been knocked out show distinct malformations and lethality....
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.059071
更新日期:2010-02-01 00:00:00
abstract::Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00