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Pharmacological Research Dec 1991
Review
Topics: Animals; Down-Regulation; In Vitro Techniques; Muscle Contraction; Muscle, Smooth, Vascular; Receptors, Adrenergic, alpha; Signal Transduction; Up-Regulation
PubMed: 1666672
DOI: 10.1016/1043-6618(91)90035-v -
Biomolecules Jun 2021Adrenergic receptors are G protein-coupled receptors for epinephrine and norepinephrine. They are targets of many drugs for various conditions, including treatment of... (Review)
Review
Adrenergic receptors are G protein-coupled receptors for epinephrine and norepinephrine. They are targets of many drugs for various conditions, including treatment of hypertension, hypotension, and asthma. Adrenergic receptors are intensively studied in structural biology, displayed for binding poses of different types of ligands. Here, we summarized molecular mechanisms of ligand recognition and receptor activation exhibited by structure. We also reviewed recent advances in structure-based ligand discovery against adrenergic receptors.
Topics: Adrenergic Agonists; Adrenergic Antagonists; Amino Acid Sequence; Animals; Crystallography, X-Ray; Epinephrine; Humans; Ligands; Norepinephrine; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Receptors, Adrenergic
PubMed: 34202543
DOI: 10.3390/biom11070936 -
Psychosomatic Medicine 1993For years research in fields such as biologic psychiatry and hypertension has benefited from the use of receptor measures. It is only recently however, that... (Review)
Review
For years research in fields such as biologic psychiatry and hypertension has benefited from the use of receptor measures. It is only recently however, that investigators in the field of psychosomatic medicine have taken advantage of this methodology. Much of this research revolves around discerning the roles that adrenergic receptors play in stressful events and stress-related behaviors. Thus far, psychosomatic studies have focused primarily on three areas: 1) The effects of psychosocial stressors on adrenergic receptor function, 2) the relationship between adrenergic receptors and cardiovascular responses to stressors, and 3) the relationship between adrenergic receptor measures and coronary-prone behaviors. Although several important methodological issues need to be addressed, current studies are helping to decipher longstanding questions regarding the complex processes underlying behavior, stress, immunity, and the sympathetic nervous system. This paper reviews the progress and limitations of this research blossoming field.
Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Emotions; Humans; Receptors, Adrenergic; Stress, Psychological
PubMed: 8265747
DOI: 10.1097/00006842-199309000-00008 -
ReceptorG-protein-linked transmembrane signaling is a major mechanism for processing information across biological membranes. Receptors that propagate signals from ligand... (Review)
Review
G-protein-linked transmembrane signaling is a major mechanism for processing information across biological membranes. Receptors that propagate signals from ligand binding to effector units via G-proteins are a populous class, including receptors for hormones, neurotransmitters, and autacoids. Much information has emerged on the structure of receptors, G-proteins, and effectors. Relatively little is known of the molecular basis underlying physiological regulation. The present article highlights the many recent advances that have permitted more detailed analysis of the regulation of one prominent member of the G-protein-linked receptor family, the beta-adrenergic receptor. Dynamic regulation of receptor function and expression is discussed with emphasis on the processes of desensitization and downregulation by agonist as well as up-regulation in response to steroids. Data are gleaned from studies of the biochemistry, cell, and molecular biology of beta-adrenergic receptors to provide a current model for discussion of receptor regulation.
Topics: Amino Acid Sequence; Animals; Cell Membrane; Down-Regulation; GTP-Binding Proteins; Humans; Molecular Sequence Data; Receptors, Adrenergic, beta; Signal Transduction; Up-Regulation
PubMed: 1967095
DOI: No ID Found -
The Journal of Allergy and Clinical... Aug 1999The beta(2 )-adrenergic receptor has been cloned, mutated, and recombinantly expressed such that many structural features involved in receptor function have been... (Review)
Review
The beta(2 )-adrenergic receptor has been cloned, mutated, and recombinantly expressed such that many structural features involved in receptor function have been defined. Agonists bind in a pocket formed by transmembrane spanning domains 3, 5, and 6, where key contact points initiate receptor activation. An interaction with the beta-hydroxyl group of beta-agonists and Asn293 of the latter transmembrane domain is the basis of the stereoselectivity of R- vs S-isomers of catecholamine-like agonists. Sites within the receptor that serve to dampen the signal with continuous agonist exposure have also been identified and include sites for phosphorylation by protein kinase A and G-protein-coupled receptor kinases and structural features that direct the receptor toward degradation (downregulation). Several regions of the beta(2 )-adrenergic receptor show genetic diversity within the human population, such that expression, coupling, and agonist regulation may be different in individuals with these polymorphisms.
Topics: Adrenergic beta-Agonists; Amino Acid Sequence; Animals; Down-Regulation; Humans; Molecular Sequence Data; Phosphorylation; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Signal Transduction; Structure-Activity Relationship
PubMed: 10452787
DOI: 10.1016/s0091-6749(99)70272-1 -
Journal of the American Veterinary... Nov 1984Recent advances in basic biomedical research have led to the development of clinically useful drugs known as "second generation" adrenergic receptor stimulants... (Review)
Review
Recent advances in basic biomedical research have led to the development of clinically useful drugs known as "second generation" adrenergic receptor stimulants (agonists) and blockers (antagonists). Adrenergic receptors are now differentiated into 4 distinct subtypes: alpha 1, alpha 2, beta 1, and beta 2. The new drugs are more receptor-selective and tissue-specific than older ones and, hence, have increased potential for directed therapeutic action, with relatively less side effects on nontargeted organs. The beta 2-selective agonist terbutaline, eg, causes bronchodilation with less beta 1-cardiac excitation than does the beta 1-beta 2 nonselective agonist isoproterenol. Compared with the latter, the beta 1-selective agonist dobutamine increases myocardial contractile force and cardiac output with less beta 2-mediated vasodilation and hypotension. The beta 1-selective antagonist metoprolol has advantage over the beta 1-beta 2 nonselective blocker propranolol for controlling beta 1-cardiac excitation in patients with compromised pulmonary function. Prazosin, an alpha 1-selective blocking agent, evokes peripheral vasodilation with less reflex tachycardia than does the nonselective alpha 1-alpha 2 blocker phentolamine, probably because the former spares the prejunctional alpha 2-receptors that subserve autoinhibition of norepinephrine release from the sympathetic neuron. The contemporary practice of internal medicine will no doubt include an understanding of the pharmacologic properties associated with the various adrenergic receptor subtypes.
Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Cardiovascular Diseases; Dogs; Dose-Response Relationship, Drug; Lung Diseases; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Receptors, Dopamine; Sympathomimetics; Synaptic Transmission
PubMed: 6150925
DOI: No ID Found -
The Journal of Biological Chemistry Apr 1997Rapid regulation of G protein-coupled receptors appears to involve agonist-promoted receptor phosphorylation by G protein-coupled receptor kinases (GRKs). This is...
Rapid regulation of G protein-coupled receptors appears to involve agonist-promoted receptor phosphorylation by G protein-coupled receptor kinases (GRKs). This is followed by binding of uncoupling proteins termed arrestins and transient receptor internalization. In this report we show that the beta-adrenergic receptor kinase (betaARK-1 or GRK2) follows a similar pattern of internalization upon agonist activation of beta2-adrenergic receptors (beta2AR) and that betaARK expression levels modulate receptor sequestration. Stable cotransfected cells expressing an epitope-tagged beta2AR and betaARK-1 show an increased rate and extent of beta2AR internalization compared with cells expressing receptor alone. Moreover, subcellular gradient fractionation studies suggest that betaARK colocalizes with the internalized receptors. In fact, double immunofluorescence analysis using confocal microscopy shows extensive colocalization of beta2AR and betaARK in intracellular vesicles upon receptor stimulation. Our results confirm a functional relationship between receptor phosphorylation and sequestration and indicate that betaARK does not only translocates from the cytoplasm to the plasma membrane in response to receptor occupancy, but shares endocytic mechanisms with the beta2AR. These data suggest a direct role for betaARK in the sequestration process and/or the involvement of receptor internalization in the intracellular trafficking of the kinase.
Topics: Adrenergic beta-Agonists; Cell Line; Cyclic AMP-Dependent Protein Kinases; Fluorescent Antibody Technique; Humans; Isoproterenol; Microscopy, Confocal; Receptors, Adrenergic, beta; Receptors, Adrenergic, beta-1; Receptors, Adrenergic, beta-2; beta-Adrenergic Receptor Kinases
PubMed: 9092483
DOI: 10.1074/jbc.272.15.9601 -
Nihon Rinsho. Japanese Journal of... Jul 2006
Review
Topics: Alleles; Animals; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Humans; Hypertension; Mutation; Polymorphism, Genetic; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, alpha-2; Receptors, Presynaptic
PubMed: 16897877
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... Jul 2006
Review
Topics: Humans; Hypertension; Polymorphism, Genetic; Receptors, Adrenergic, beta
PubMed: 16895203
DOI: No ID Found -
Methods in Molecular Biology (Clifton,... 2000
Review
Topics: Animals; Humans; Receptors, Adrenergic
PubMed: 10685401
DOI: 10.1385/1-59259-684-3:37