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  • 1
    Publication Date: 1996-08-09
    Description: alpha2-Adrenergic receptors (alpha2ARs) present in the brainstem decrease blood pressure and are targets for clinically effective antihypertensive drugs. The existence of three alpha2AR subtypes, the lack of subtype-specific ligands, and the cross-reactivity of alpha2AR agonists with imidazoline receptors has precluded an understanding of the role of individual alpha2AR subtypes in the hypotensive response. Gene targeting was used to introduce a point mutation into the alpha2aAR subtype in the mouse genome. The hypotensive response to alpha2AR agonists was lost in the mutant mice, demonstrating that the alpha2aAR subtype plays a principal role in this response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacMillan, L B -- Hein, L -- Smith, M S -- Piascik, M T -- Limbird, L E -- HL38120/HL/NHLBI NIH HHS/ -- HL43671/HL/NHLBI NIH HHS/ -- HL48638/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 9;273(5276):801-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8670421" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic alpha-2 Receptor Agonists ; Adrenergic alpha-Agonists/pharmacology ; Animals ; Antihypertensive Agents/pharmacology ; Base Sequence ; Blood Pressure/drug effects/*physiology ; Brain Stem/physiology ; Brimonidine Tartrate ; Gene Targeting ; Heart Rate/drug effects/physiology ; Imidazoles/pharmacology ; Medetomidine ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Point Mutation ; Quinoxalines/pharmacology ; Receptors, Adrenergic, alpha-2/genetics/metabolism/*physiology
    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
    Publication Date: 1996-08-09
    Description: alpha2-Adrenergic receptors (alpha2ARs) are essential components of the neural circuitry regulating cardiovascular function. The role of specific alpha2AR subtypes (alpha2a, alpha2b, and alpha2c) was characterized with hemodynamic measurements obtained from strains of genetically engineered mice deficient in either alpha2b or alpha2c receptors. Stimulation of alpha2b receptors in vascular smooth muscle produced hypertension and counteracted the clinically beneficial hypotensive effect of stimulating alpha2a receptors in the central nervous system. There were no hemodynamic effects produced by disruption of the alpha2c subtype. These results provide evidence for the clinical efficacy of more subtype-selective alpha2AR drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Link, R E -- Desai, K -- Hein, L -- Stevens, M E -- Chruscinski, A -- Bernstein, D -- Barsh, G S -- Kobilka, B K -- GM07365/GM/NIGMS NIH HHS/ -- HL48638/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 9;273(5276):803-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8670422" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic alpha-Agonists/pharmacology ; Adrenergic alpha-Antagonists/metabolism/pharmacology ; Animals ; Blood Pressure/drug effects/*physiology ; Gene Targeting ; Heart Rate/drug effects/*physiology ; Imidazoles/pharmacology ; Kidney/metabolism ; Medetomidine ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Knockout ; Muscle, Smooth, Vascular/metabolism ; Phenylephrine/pharmacology ; Prazosin/pharmacology ; Receptors, Adrenergic, alpha-2/genetics/*physiology ; Yohimbine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
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