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  • Articles  (32)
  • Dose-Response Relationship, Drug
  • American Association for the Advancement of Science (AAAS)  (32)
  • American Geophysical Union
  • American Meteorological Society
  • American Physical Society (APS)
  • International Union of Crystallography (IUCr)
  • Springer Nature
  • 2010-2014
  • 2000-2004
  • 1995-1999  (7)
  • 1985-1989
  • 1980-1984  (25)
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  • 1955-1959
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  • 1999  (7)
  • 1983  (25)
  • 1958
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  • Science. 219(4582): 236-8.  (1)
  • Science. 219(4588): 1032-7.  (1)
  • Science. 219(4588): 1075-7.  (1)
  • Science. 219(4589): 1221-3.  (1)
  • Science. 220(4592): 69-70.  (1)
  • Science. 220(4592): 99-101.  (1)
  • Science. 220(4594): 333-5.  (1)
  • Science. 220(4596): 517-9.  (1)
  • Science. 220(4596): 534-6.  (1)
  • Science. 220(4600): 957-8.  (1)
  • Science. 220(4601): 1053-5.  (1)
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  • Science. 220(4601): 1073-4.  (1)
  • Science. 220(4602): 1163-4.  (1)
  • Science. 221(4605): 71-3.  (1)
  • Science. 221(4606): 192-3.  (1)
  • Science. 221(4611): 659-61.  (1)
  • Science. 221(4611): 671-3.  (1)
  • Science. 221(4615): 1059-61.  (1)
  • Science. 221(4617): 1244-6.  (1)
  • 25
  • Natural Sciences in General  (32)
  • Biology  (32)
  • Medicine  (32)
Collection
  • Articles  (32)
Source
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  • American Association for the Advancement of Science (AAAS)  (32)
  • American Geophysical Union
  • American Meteorological Society
  • American Physical Society (APS)
  • International Union of Crystallography (IUCr)
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  • 2010-2014
  • 2000-2004
  • 1995-1999  (7)
  • 1985-1989
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  • 1
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    Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-01-05
    Description: Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ikonomidou, C -- Bosch, F -- Miksa, M -- Bittigau, P -- Vockler, J -- Dikranian, K -- Tenkova, T I -- Stefovska, V -- Turski, L -- Olney, J W -- AG 11355/AG/NIA NIH HHS/ -- DA 05072/DA/NIDA NIH HHS/ -- MH 38894/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):70-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Neurology, Charite-Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. hrissanthi.ikonomidou@charite.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9872743" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Brain/*cytology/drug effects/embryology/growth & development ; Calcium Channel Blockers/pharmacology ; Dizocilpine Maleate/pharmacology ; Dopamine Antagonists/pharmacology ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists/pharmacology ; Fetus ; Haloperidol/pharmacology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Microscopy, Electron ; Muscarinic Antagonists/pharmacology ; *Nerve Degeneration ; Neurons/*cytology/drug effects/metabolism ; Quinoxalines/pharmacology ; Rats ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/metabolism ; Scopolamine Hydrobromide/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Transmission of chronic nociception by spinal neurons expressing the substance P receptor (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-11-24
    Description: Substance P receptor (SPR)-expressing spinal neurons were ablated with the selective cytotoxin substance P-saporin. Loss of these neurons resulted in a reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states. This loss appeared to be permanent. Responses to mildly painful stimuli and morphine analgesia were unaffected by this treatment. These results identify a target for treating persistent pain and suggest that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nichols, M L -- Allen, B J -- Rogers, S D -- Ghilardi, J R -- Honore, P -- Luger, N M -- Finke, M P -- Li, J -- Lappi, D A -- Simone, D A -- Mantyh, P W -- 23970/PHS HHS/ -- 31223/PHS HHS/ -- DEO 7288/DE/NIDCR NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Nov 19;286(5444):1558-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Preventive Sciences, University of Minnesota, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10567262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Ganglia, Spinal/drug effects/physiology ; *Immunotoxins ; Inflammation/physiopathology ; Ligation ; *N-Glycosyl Hydrolases ; Neuralgia/drug therapy/physiopathology ; Pain/*drug therapy/*physiopathology ; Plant Proteins/administration & dosage/*pharmacology ; Posterior Horn Cells/drug effects/*physiology ; Rats ; Receptors, Neurokinin-1/*metabolism ; Ribosome Inactivating Proteins, Type 1 ; Spinal Nerves ; Substance P/administration & dosage/*pharmacology ; Time Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Discovery of a small molecule insulin mimetic with antidiabetic activity in mice (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-05-13
    Description: Insulin elicits a spectrum of biological responses by binding to its cell surface receptor. In a screen for small molecules that activate the human insulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was selective for insulin receptor versus insulin-like growth factor I (IGFI) receptor and other receptor tyrosine kinases. Oral administration of L-783,281 to two mouse models of diabetes resulted in significant lowering in blood glucose levels. These results demonstrate the feasibility of discovering novel insulin receptor activators that may lead to new therapies for diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, B -- Salituro, G -- Szalkowski, D -- Li, Z -- Zhang, Y -- Royo, I -- Vilella, D -- Diez, M T -- Pelaez, F -- Ruby, C -- Kendall, R L -- Mao, X -- Griffin, P -- Calaycay, J -- Zierath, J R -- Heck, J V -- Smith, R G -- Moller, D E -- New York, N.Y. -- Science. 1999 May 7;284(5416):974-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Endocrinology, Merck Research Laboratories, R80W250, Post Office Box 2000, Rahway, NJ 07065, USA. bei_zhang@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320380" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Ascomycota/*metabolism ; Binding Sites ; Blood Glucose/metabolism ; CHO Cells ; Cricetinae ; Diabetes Mellitus, Type 2/*drug therapy ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Enzyme Activation ; Glucose Tolerance Test ; Hyperglycemia/drug therapy ; Hypoglycemic Agents/chemistry/metabolism/*pharmacology/therapeutic use ; Indoles/chemistry/metabolism/*pharmacology/therapeutic use ; Insulin/blood/metabolism/*pharmacology ; Insulin Receptor Substrate Proteins ; Mice ; Mice, Mutant Strains ; Mice, Obese ; Molecular Mimicry ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Conformation/drug effects ; Receptor, Epidermal Growth Factor/metabolism ; Receptor, IGF Type 1/metabolism ; Receptor, Insulin/chemistry/*metabolism ; Signal Transduction
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Genetic variation in susceptibility to endocrine disruption by estrogen in mice (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-08-24
    Description: Large (more than 16-fold) differences in susceptibility to disruption of juvenile male reproductive development by 17beta-estradiol (E2) were detected between strains of mice. Effects of strain, E2 dose, and the interaction of strain and E2 dose on testes weight and spermatogenesis were all highly significant (P 〈 0.0001). Spermatid maturation was eliminated by low doses of E2 in strains such as C57BL/6J and C17/Jls. In contrast, mice of the widely used CD-1 line, which has been selected for large litter size, showed little or no inhibition of spermatid maturation even in response to 16 times as much E2. Product safety bioassays conducted with animals selected for fecundity may greatly underestimate disruption of male reproductive development by estradiol and environmental estrogenic compounds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spearow, J L -- Doemeny, P -- Sera, R -- Leffler, R -- Barkley, M -- New York, N.Y. -- Science. 1999 Aug 20;285(5431):1259-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Neurobiology, Physiology and Behavior, University of California at Davis, Davis, CA 95616, USA. jlspearow@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10455051" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Weight/drug effects ; Dose-Response Relationship, Drug ; Estradiol/*pharmacology/toxicity ; *Genetic Variation ; Litter Size ; Male ; Mice ; Mice, Inbred Strains ; Organ Size/drug effects ; Species Specificity ; Spermatids/drug effects ; Spermatogenesis/*drug effects ; Testis/anatomy & histology/*drug effects ; Toxicity Tests
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-10-09
    Description: Many human diseases are associated with the overproduction of oxygen free radicals that inflict cell damage. A manganese(II) complex with a bis(cyclohexylpyridine)-substituted macrocyclic ligand (M40403) was designed to be a functional mimic of the superoxide dismutase (SOD) enzymes that normally remove these radicals. M40403 had high catalytic SOD activity and was chemically and biologically stable in vivo. Injection of M40403 into rat models of inflammation and ischemia-reperfusion injury protected the animals against tissue damage. Such mimics may result in better clinical therapies for diseases mediated by superoxide radicals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Salvemini, D -- Wang, Z Q -- Zweier, J L -- Samouilov, A -- Macarthur, H -- Misko, T P -- Currie, M G -- Cuzzocrea, S -- Sikorski, J A -- Riley, D P -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):304-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MetaPhore Pharmaceuticals, 1910 Innerbelt Business Center Drive, St. Louis, MO 63114, USA. dsalvemini@metaphore.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514375" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical ; synthesis/chemistry/metabolism/*therapeutic use ; Cytoprotection ; Dinoprostone/metabolism ; Dose-Response Relationship, Drug ; Drug Design ; Drug Stability ; Inflammation/*drug therapy ; Interleukin-1/metabolism ; L-Lactate Dehydrogenase/metabolism ; Male ; Manganese ; Molecular Mimicry ; Neutrophils/drug effects ; Organometallic Compounds/chemical synthesis/chemistry/metabolism/*toxicity ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/*drug therapy ; Splanchnic Circulation ; *Superoxide Dismutase/metabolism ; Superoxides/*metabolism ; Time Factors ; Tumor Necrosis Factor-alpha/metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Enhanced cortical dopamine output and antipsychotic-like effects of raclopride by alpha2 adrenoceptor blockade (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-10-03
    Description: Clozapine exerts superior clinical efficacy and markedly enhances cortical dopamine output compared with classical antipsychotic drugs. Here the alpha2 adrenoceptor antagonist idazoxan was administered to rats alone or in combination with the D2/3 dopamine receptor antagonist raclopride. Dopamine efflux in the medial prefrontal cortex and conditioned avoidance responding were analyzed. Idazoxan selectively potentiated the cortical output of dopamine and augmented the suppression of conditioned avoidance responding induced by raclopride. These results challenge basic assumptions underlying the dopamine hypothesis of schizophrenia and provide insight into clozapine's mode of action.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hertel, P -- Fagerquist, M V -- Svensson, T H -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):105-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10506554" target="_blank"〉PubMed〈/a〉
    Keywords: *Adrenergic alpha-2 Receptor Antagonists ; Adrenergic alpha-Antagonists/pharmacology ; Animals ; Antipsychotic Agents/*pharmacology ; Avoidance Learning/drug effects ; Catalepsy/chemically induced ; Conditioning (Psychology) ; Corpus Striatum/drug effects/metabolism ; Dopamine/*metabolism ; Dopamine Antagonists/*pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Idazoxan/*pharmacology ; Nucleus Accumbens/drug effects/metabolism ; Prefrontal Cortex/*drug effects/metabolism ; Raclopride ; Rats ; Receptors, Adrenergic, alpha-2/metabolism ; Salicylamides/*pharmacology ; Schizophrenia/drug therapy/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-12-22
    Description: Resistance to antibiotics is increasing in some groups of clinically important pathogens. For instance, high vancomycin resistance has emerged in enterococci. Promising alternative antibiotics are the peptide antibiotics, abundant in host defense systems, which kill their targets by permeabilizing the plasma membrane. These peptides generally do not act via specific receptors and are active in the micromolar range. Here it is shown that vancomycin and the antibacterial peptide nisin Z use the same target: the membrane-anchored cell wall precursor Lipid II. Nisin combines high affinity for Lipid II with its pore-forming ability, thus causing the peptide to be highly active (in the nanomolar range).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breukink, E -- Wiedemann, I -- van Kraaij, C -- Kuipers, O P -- Sahl, H G -- de Kruijff, B -- New York, N.Y. -- Science. 1999 Dec 17;286(5448):2361-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center of Biomembranes and Lipid Enzymology, Department of Biochemistry of Membranes, Institute for Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10600751" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anti-Bacterial Agents/metabolism/*pharmacology ; Cell Membrane/drug effects/metabolism ; Cell Membrane Permeability/drug effects ; Cell Wall/metabolism ; Dose-Response Relationship, Drug ; Membrane Lipids/metabolism ; Microbial Sensitivity Tests ; Micrococcus/*drug effects/metabolism ; Molecular Sequence Data ; Nisin/*analogs & derivatives/metabolism/pharmacology ; Peptides/pharmacology ; Peptidoglycan ; Polyisoprenyl Phosphate Oligosaccharides/*metabolism ; Vancomycin/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Alcohol and pregnancy (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 1983 Sep 23;221(4617):1244-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6684327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Ethanol/*adverse effects ; Female ; Pregnancy ; Pregnancy, Animal/*drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    Platelet thromboxane synthetase inhibitors with low doses of aspirin: possible resolution of the "aspirin dilemma" (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-04-29
    Description: Selective pharmacological inhibition of thromboxane A2 synthesis did not prevent arachidonate-induced aggregation of human platelets in vitro. Prevention was instead achieved by a combination of thromboxane A2 inhibitors with low concentrations of aspirin. The latter partially reduced the proaggregatory cyclooxygenase products that accumulated when thromboxane A2 synthesis was blocked. The aspirin concentrations did not affect per se either platelet aggregation or prostacyclin synthesis in cultured human endothelial cells. The combination of thromboxane synthetase inhibitors with low doses of aspirin may offer greater antithrombotic potential than either drug alone.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bertele, V -- Falanga, A -- Tomasiak, M -- Dejana, E -- Cerletti, C -- de Gaetano, G -- New York, N.Y. -- Science. 1983 Apr 29;220(4596):517-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6682245" target="_blank"〉PubMed〈/a〉
    Keywords: Aspirin/*pharmacology ; Blood Platelets/*drug effects/enzymology ; Dose-Response Relationship, Drug ; Drug Interactions ; Humans ; Imidazoles/pharmacology ; Methacrylates/pharmacology ; Oxidoreductases/*antagonists & inhibitors ; Platelet Aggregation/drug effects ; Thromboxane-A Synthase/*antagonists & inhibitors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-07-01
    Description: Mammalian atrial extracts possess natriuretic and diuretic activity. In experiments reported here it was found that atrial, but not ventricular, extract also causes relaxation of isolated vascular and nonvascular smooth muscle preparations. The smooth muscle relaxant activity of atrial extract was heat-stable and concentration-dependent and could be destroyed with protease. Rabbit aortic and chick rectum strips were used for the detection of atrial biological activity. The atrial activity was separated by column chromatography into two peaks having apparent molecular weights of 20,000 to 30,000 and less than 10,000. The atrial substance that copurified with the smooth muscle relaxant activity in both peaks caused natriuresis when injected into conscious rats. It appears that atria possess at least two peptides that elicit smooth muscle relaxation and natriuresis, suggesting an endogenous system of fluid volume regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Currie, M G -- Geller, D M -- Cole, B R -- Boylan, J G -- YuSheng, W -- Holmberg, S W -- Needleman, P -- New York, N.Y. -- Science. 1983 Jul 1;221(4605):71-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6857267" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atrial Function ; Chickens ; Chromatography, Gel ; Dogs ; Dose-Response Relationship, Drug ; Humans ; Molecular Weight ; Muscle, Smooth/drug effects ; Muscle, Smooth, Vascular/*drug effects ; Natriuresis/drug effects ; Rabbits ; Rats ; Swine ; Vasodilation/drug effects
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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