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Life Sciences 1995Alpha 1 (alpha 1)-adrenoceptors can be found at numerous end organs in the autonomic nervous system, especially vascular smooth muscle. The tonic sympathetic activation... (Review)
Review
Alpha 1 (alpha 1)-adrenoceptors can be found at numerous end organs in the autonomic nervous system, especially vascular smooth muscle. The tonic sympathetic activation of vascular alpha 1-adrenoceptors maintains vascular resistance and is vital to the regulation of arterial pressure. Recent evidence clearly demonstrates that alpha 1-adrenoceptors are a heterogenous class of receptors and that each subtype may subserve specific cardiovascular functions. Elucidation of the physiological role of each subtype in the regulation of vascular resistance and arterial pressure will enhance our understanding of the cardiovascular system and may facilitate the development of therapeutics with improved efficacy and tolerability.
Topics: Animals; Blood Pressure; Blood Vessels; Humans; Receptors, Adrenergic, alpha-1
PubMed: 7491088
DOI: 10.1016/0024-3205(95)02224-7 -
The American Journal of Psychiatry May 1979In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and...
In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and isoproterenol (IP) in leukocytes of patients with affective illness and schizophrenia and of normal controls. IP-stimulated increase in 3H-cyclic AMP synthesis in depressed patients was significantly lower than in normal subjects and schizophrenic patients. These results suggest that beta-adrenergic receptor sensitivity is reduced in depressive illness.
Topics: Adenylyl Cyclases; Bipolar Disorder; Cyclic AMP; Depression; Dose-Response Relationship, Drug; Humans; Isoproterenol; Leukocytes; Norepinephrine; Prostaglandins E; Receptors, Adrenergic; Receptors, Adrenergic, beta; Schizophrenia
PubMed: 219719
DOI: 10.1176/ajp.136.5.675 -
Annual Review of Pharmacology and... 1992
Review
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Mutagenesis; Receptors, Adrenergic, beta; Structure-Activity Relationship
PubMed: 1318669
DOI: 10.1146/annurev.pa.32.040192.001123 -
Cellular Physiology and Biochemistry :... Sep 2020Trace amines (TA) are small organic compounds that have neuromodulator activity due to their interaction with some neuron-related receptors, such as trace amine...
BACKGROUND/AIMS
Trace amines (TA) are small organic compounds that have neuromodulator activity due to their interaction with some neuron-related receptors, such as trace amine associated receptors (TAARs), α2-adrenergic receptor (α2-AR) and ß-adrenergic receptor (ß-AR). However, there is little information on whether TA and dopamine (DOP) can interact with other adrenergic receptors (ARs) such as the mammalian α1-AR and the bacterial counterpart QseC, which is involved in quorum sensing of some Gram-negative pathogens. The aim of this study was to investigate the interaction of TA and DOP with α1-AR and QseC.
METHODS
We performed an in silico study using 3D structure from SWISS MODEL and analyzed the protein interaction via molecular docking using PyMol, PoseView and PyRX 8.0. For the in vitro study, we investigated the QseC kinase activity by measuring the remaining ATP in a reaction containing QseC-enriched membrane incubated together with purified QseB and EPI, TA, DOP, or PTL respectively. We also measured the intracellular Ca++ levels, which represents the α1-AR activation, in LNCAP (pancreatic cell line) cells treated with EPI, TA, DOP and PTL respectively using a fluorescence-based assay. The LNCAP cell proliferation was measured using an MTT-based assay.
RESULTS
Our in silico analysis revealed that TAs and DOP have high binding affinity to the human α1-AR and the bacterial adrenergic receptor (QseC), comparable to epinephrine (EPI). Both are membrane-bound kinases. Experimental studies with pancreatic cell line (LNCAP) showed that the TAs and DOP act as α1-AR antagonist by counteracting the effect of EPI. In the presence of EPI, TA and DOP trigger an increase of the intracellular Ca++ levels in the LNCAP cells leading to an inhibition of cell proliferation. Although in silico data suggest an interaction of TA and DOP with QseC, they do not inhibit the kinase activity of QseC, a histidine kinase receptor involved in quorum sensing which is also sensitive to EPI.
CONCLUSION
Our study showed that the TAs and DOP act as α1-AR antagonist but no effect was observed for QseC.
Topics: Amines; Animals; Computer Simulation; Dopamine; Escherichia coli Proteins; Humans; Molecular Docking Simulation; Phosphorylation; Receptors, Adrenergic, alpha-1; Signal Transduction; Trace Elements
PubMed: 32930525
DOI: 10.33594/000000276 -
Journal of Neural Transmission. General... 1990Pineal adrenergic receptor numbers show circadian variations in both rat and Syrian hamster. In the rat pineal beta-adrenergic receptor density reaches peak values... (Review)
Review
Pineal adrenergic receptor numbers show circadian variations in both rat and Syrian hamster. In the rat pineal beta-adrenergic receptor density reaches peak values either late in the light phase or at middark; the differences in the circadian phase seem related to the light:dark cycle to which the animals are exposed. No circadian rhythm of pineal alpha-adrenergic receptors is documented in intact rats. In the Syrian hamster pineal beta-adrenergic receptor density is high throughout the light phase and drops to minimal values at the time of the nocturnal peak of melatonin production. The circadian rhythm of pineal alpha-adrenergic receptor numbers runs parallel to the beta-adrenergic receptor variation, but is less pronounced. In the rat, pineal melatonin production is rapidly induced by beta-adrenergic agonists at any time during a 24-hour period, even when the pinealocyte beta-adrenergic receptor number is lowest (early in the light phase). In contrast, the Syrian hamster pineal seems most responsive to beta-adrenergic agonists in the late night while being less responsive during the day when beta-adrenergic receptor density is high. Interestingly, the human pineal gland is also not especially responsive to adrenergic stimulation during the light phase, possibly making the Syrian hamster pineal a better model than the rat pineal for determining neural/pineal interactions in humans. Comparison of the circadian variations in pineal adrenergic receptors leads to the conclusion that the functional differences between rat and hamster pineal are probably not explicable in terms of the adrenergic receptors, but are caused most likely by (a) intracellular mechanism(s) beyond the adrenergic receptors.
Topics: Animals; Circadian Rhythm; Cricetinae; Mesocricetus; Pineal Gland; Rats; Receptors, Adrenergic, beta
PubMed: 2162676
DOI: 10.1007/BF01245442 -
Journal of Cardiothoracic and Vascular... Feb 1998
Review
Topics: Adrenergic beta-Antagonists; Animals; Cardiovascular System; Critical Care; Heart Failure; Heart Transplantation; Humans; Receptors, Adrenergic; Signal Transduction
PubMed: 9509364
DOI: 10.1016/s1053-0770(98)90062-3 -
Biochemical Pharmacology Apr 2007The current manuscript reviews the evidence whether and how subtypes of alpha(1)-adrenergic receptors, i.e. alpha(1A)-, alpha(1B)- and alpha(1D)-adrenergic receptors,... (Review)
Review
The current manuscript reviews the evidence whether and how subtypes of alpha(1)-adrenergic receptors, i.e. alpha(1A)-, alpha(1B)- and alpha(1D)-adrenergic receptors, differentially couple to signal transduction pathways and exhibit differential susceptibility to regulation. In both regards studies in tissues or cells natively expressing the subtypes are hampered because the relative expression of the subtypes is poorly controlled and the observed effects may be cell-type specific. An alternative approach, i.e. transfection of multiple subtypes into the same host cell line overcomes this limitation, but it often remains unclear whether results in such artificial systems are representative for the physiological situation. The overall evidence suggests that indeed subtype-intrinsic and cell type-specific factors interact to direct alpha(1)-adrenergic receptor signaling and regulation. This may explain why so many apparently controversial findings have been reported from various tissues and cells. One of the few consistent themes is that alpha(1D)-adrenergic receptors signal less effectively upon agonist stimulation than the other subtypes, most likely because they exhibit spontaneous internalization.
Topics: Animals; Cell Physiological Phenomena; Down-Regulation; Gene Expression Regulation; Humans; Receptors, Adrenergic, alpha-1; Signal Transduction
PubMed: 17141737
DOI: 10.1016/j.bcp.2006.11.001 -
The American Journal of the Medical... Oct 2015Heightened cardiac adrenergic nervous system (ANS) activity and progression of left ventricular (LV) remodeling are temporally related in patients with systolic heart... (Review)
Review
Heightened cardiac adrenergic nervous system (ANS) activity and progression of left ventricular (LV) remodeling are temporally related in patients with systolic heart failure. Whether cardiac ANS activation directly contributes to or merely accompanies LV remodeling remains an unresolved issue. Human and experimental data that directly link cardiac ANS activation to LV remodeling and worsening heart failure are first reviewed, including cardiac norepinephrine spillover. Alterations of beta adrenergic receptor signaling pathways are then addressed with emphasis on the mechanisms that may mediate the beneficial effect of beta adrenergic receptor blockade on LV remodeling. Lastly, alternative approaches to beta adrenergic receptor blockade for lessening cardiac ANS activation and reversing cardiac ANS-induced LV remodeling are discussed. A large body of work now links LV remodeling to cardiac ANS activation. However, the precise mechanisms that link cardiac ANS activation to LV remodeling are still to be fully understood. Fully understanding of these mechanisms may uncover new therapeutic approaches.
Topics: Adrenergic Agents; Cardiology; Disease Progression; Heart; Heart Failure; Humans; Nervous System; Phosphorylation; Receptors, Adrenergic; Receptors, Adrenergic, beta; Signal Transduction; Ventricular Remodeling
PubMed: 26332730
DOI: 10.1097/MAJ.0000000000000549 -
Cardiovascular Drugs and Therapy Dec 2000In vitro lipolysis stimulated by low (-)-isoprenaline concentrations (< or =30 nM) in epididymal white adipocytes from Sprague-Dawley rats was inhibited at least 60-80%...
In vitro lipolysis stimulated by low (-)-isoprenaline concentrations (< or =30 nM) in epididymal white adipocytes from Sprague-Dawley rats was inhibited at least 60-80% by the specific beta1-antagonists LK 204-545 and CGP 20712A (1 microM), suggesting that at these low (10 nM) concentrations of (-)-isoprenaline lipolysis was primarily (80%) but not solely mediated via beta1-adrenergic receptors. Low concentrations (100 nM) of (-)-noradrenaline and formoterol also confirmed a role for beta1-adrenergic receptors in mediating lipolysis at low concentrations of these agonists. At higher agonist concentrations, beta3-adrenergic receptors were fully activated and were the dominant beta-adrenergic receptor subtype mediating the maximum lipolytic response, and the maximum response was not affected by the beta1-antagonists, demonstrating that the beta3-receptor is capable of inducing maximum lipolysis on its own. Studies of lipolysis induced by the relatively beta2-selective agonist formoterol in the presence of beta1-blockade (1 microM CGP 20712A) demonstrated the inability of the beta2-selective antagonist ICI 118-551 to inhibit the residual lipolysis at concentrations of ICI 118-551 < or = 1 microM. Higher concentrations of ICI 118-551 inhibited the residual formoterol-induced lipolysis competetively, but with low affinity (approximately 500-fold lower than its beta2-adrenergic receptor pA2, 7.80 +/- 0.21), suggesting that formoterol was not acting via beta2-adrenergic receptors. These data are consistent with beta1-adrenergic receptors playing an important role in lipolysis at physiological but not pharmacological concentrations of catecholamines and that beta2-adrenergic receptors play no obvious direct role in mediating beta-adrenergic receptor agonist-induced lipolysis in vitro. Finally, racemic-SR 59230A, unlike the pure (S, S)-isomer (a beta3-selective antagonist), was found to be a nonselective antagonist at the three beta-adrenergic receptor subtypes, showing that the other enantiomers have different selectivity.
Topics: Adipocytes; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Dose-Response Relationship, Drug; Female; Heart Rate; In Vitro Techniques; Lipolysis; Male; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta; Receptors, Adrenergic, beta-1; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-3
PubMed: 11300357
DOI: 10.1023/a:1007838125152 -
Methods in Molecular Biology (Clifton,... 2000
Review
Topics: Animals; DNA, Antisense; Humans; RNA, Antisense; Receptors, Adrenergic
PubMed: 10685416
DOI: 10.1385/1-59259-684-3:241