Adrenergic receptors are members of the G-protein coupled receptor superfamily. Recent studies revealed that these adrenergic receptors are playing an important role in the growth and metastasis of prostate cancer cells. The expression of adrenergic receptors rises significantly in prostate cancer cells and tissues. Agonists of these receptors promote the growth and mobility of prostate cancer cells, while antagonists may suppress their proliferation, trigger their apoptosis, and inhibit their metastasis. Clinically, receptor antagonists can significantly reduce the risk of prostate cancer and improve its prognosis after androgen depravation therapy. This article presents an overview on the roles of adrenergic receptors in prostate cancer.
Adrenergic Agonists ; pharmacology ; Adrenergic Antagonists ; pharmacology ; Apoptosis ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, Adrenergic ; drug effects ; physiology

A large number of β-adrenergic receptor (β-AR) agonists and antagonists are widely used in the treatment of cardiovascular diseases and other diseases. Nonetheless, it remains unclear whether these commonly used β-AR drugs can activate downstream β- arrestin-biased signaling pathways. The objective of this study was to investigate β-arrestin2 recruitment effects of β-AR agonists and antagonists that were commonly used in clinical practice. We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene. Upon activation of β-AR by a β-AR ligand, β-arrestin2 was recruited to the C terminus of the receptor, followed by cleavage of the G protein-coupled receptors (GPCRs) fusion protein at the TEV protease-cleavage site. The cleavage resulted in the release of tTA, which, after being transported to the nucleus, activated transcription of the luciferase reporter gene. The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR. β2-AR selective agonists procaterol and salbutamol promoted β-arrestin2 recruitment at β2-AR. β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands.
Humans ; beta-Arrestin 2/metabolism* ; HEK293 Cells ; Adrenergic beta-Agonists/pharmacology* ; Isoproterenol/pharmacology* ; Receptors, Adrenergic, beta-2/metabolism* ; Norepinephrine/pharmacology*

OBJECTIVETo investigate the alteration of expressions of beta(1)-, beta(2)-, beta(3)-adrenoceptor mRNA in human myocardial tissue and the relation between their expressions and cardiac function in patient with heart failure.

METHODSThe mRNA expressions of beta(1)-, beta(2)- and beta(3)-adrenergic receptors in myocardial tissue were analyzed by using the reverse transcriptase-polymerase chain reaction in 24 patients with heart failure of valvular heart disease and 5 control subjects.

RESULTSBeta(1)-adrenergic receptor mRNA expressions in myocardium were significantly lower in patients with heart failure than those in control subjects, and progressively reduced with aggravation of heart function. By contrast, beta(3)-adrenoceptor mRNA expressions were significantly higher in patients with heart failure than those in controls, and progressively elevated with aggravation of cardiac function. No difference was observed in beta(2)-adrenergic receptor among all groups.

CONCLUSIONThe changes of beta-adrenergic receptor mRNA expression are associated with the severity of heart failure.

Adult ; Case-Control Studies ; Female ; Heart Failure ; genetics ; metabolism ; physiopathology ; Humans ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Receptors, Adrenergic, beta-1 ; genetics ; metabolism ; Receptors, Adrenergic, beta-2 ; genetics ; metabolism ; Receptors, Adrenergic, beta-3 ; genetics ; metabolism

In the heart, stimulation of beta-adrenergic receptors (betaAR) serves as the most powerful means to increase cardiac contractility and relaxation in response to stress or a "fight-or-flight" situation. However, sustained beta-adrenergic stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy, apoptosis and necrosis, thus contributing to the pathogenesis of chronic heart failure. Over the past decade, compelling evidence has demonstrated that coexisting cardiac betaAR subtypes, mainly beta(1)AR and beta (2)AR, activate markedly different signaling cascades. As a result, acute beta(1)AR stimulation activates the G(s) -adenylyl cyclase-cAMP-PKA signaling that can broadcast throughout the cell, whereas beta(2)AR-evoked cAMP signaling is spatially and functionally compartmentalized, due to concurrent G(i) activation. Chronic stimulation of beta(1)AR and beta(2)AR elicits opposing effects on the fate of cardiomyocytes: beta(1)AR induces hypertrophy and apoptosis; but beta(2)AR promotes cell survival. The cardiac protective effect of beta(2)AR is mediated by a signaling pathway sequentially involving G(i), G(betagamma), PI3K and Akt. Unexpectedly, beta(1)AR-induced myocyte hypertrophy and apoptosis are independent of the classic cAMP/PKA pathway, but require activation of Ca(2+)/calmodulin-dependent kinase II (CaMK II). The outcomes of cardiac-specific transgenic overexpression of either beta AR subtype in mice have reinforced the fundamentally different functional roles of these betaAR subtypes in governing cardiac remodeling and performance. These new insights regarding betaAR subtype stimulation not only provide clues as to cellular and molecular mechanisms underlying the beneficial effects of beta AR blockers in patients with chronic heart failure, but also delineate rationale for combining selective beta(1)AR blockade with moderate beta(2)AR activation as a potential novel therapy for the treatment of chronic heart failure.
Adenylyl Cyclases ; metabolism ; Animals ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; GTP-Binding Proteins ; metabolism ; Heart ; physiology ; Heart Failure ; physiopathology ; Humans ; Myocardium ; metabolism ; Receptors, Adrenergic, beta ; classification ; physiology ; Receptors, Adrenergic, beta-1 ; physiology ; Receptors, Adrenergic, beta-2 ; physiology ; Signal Transduction

OBJECTIVETo study the interactions between Ligusticum chuanxiong Hort extract and cardiac muscle membrane receptors.

METHODThe cell membrane of rabbit cardiac muscle was fixed on silicon to make cell membrane stationary phase (CMSP), and then the interactions were studied by comparing the retention characteristics of the extracts from different solvents with those of the antagonists or activators corresponding to known receptors in cardiac muscle membrane, and by competition effect on the retention characteristics of extracts when adding the antagonists or activators into the mobile phase.

RESULTWater extract and ethanol extract both had retentions on CMSP; the retention characteristics of water extract could be affected when water extract was in competition with the antagonists for alpha receptor, and could not be affected when with the activator beta1 receptor.

CONCLUSIONIt is possible that some components in water extract may combine with alpha receptor and no component with beta1 receptor, and that some components in ethanol extract may combine with cardiac muscle cell membrane. The process between active components and receptors in vivo can be imitated through the interactions between drugs and CMSP. The method provides references for the resolution of two applications: to screen the active components from Chinese medicine, and to figure out the type of receptors involved.

Adrenergic alpha-Agonists ; metabolism ; Adrenergic alpha-Antagonists ; metabolism ; Adrenergic beta-Agonists ; metabolism ; Adrenergic beta-Antagonists ; metabolism ; Animals ; Cell Membrane ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Ligusticum ; chemistry ; Male ; Myocytes, Cardiac ; cytology ; metabolism ; Plants, Medicinal ; chemistry ; Protein Binding ; Rabbits ; Receptors, Adrenergic, alpha ; metabolism ; Receptors, Adrenergic, beta ; metabolism

OBJECTIVETo investigate the significance of beta-adrenergic receptor 2 (beta2-AR) and vascular endothelial growth factor-2 (VEGFR-2) in the occurrence and development of infantile hemangioma through detecting the expression of beta2-AR and VEGFR-2 in the different stages of infantile hemangiomas.

METHODSAccording to the Mulliken's classification standard, we classified the specimens as proliferating group (32 cases), involuting group (17 cases) and involuted group (11 cases). Normal skin tissue surrounding the hemangioma from 7 cases were chosen as control group. The expression of beta2-AR and VEGFR-2 was detected by immunohistochemical technique in proliferating hemangioma, involuting hemangioma, involuted hemangioma. The mean optical density was measured by image analysis system (Image Pro Plus 6.0) and SPSS 16.0 software was applied for statistical analysis.

RESULTSThe expression of beta2-AR and VEGFR-2 was strongly positive in proliferating hemangioma, while positive in involuting hemangioma and weakly positive in the involuted stage. The mean optical density of each phase was 0.064 751 2 +/- 0.012 747, 0.031 6017 +/- 0.006 848,0.011 869 8 +/- 0.039 349 for beta2-AR, and 0.068 940 9 +/- 0.029 274, 0.028 445 5 +/- 0.006 396, 0.011 184 1 +/- 0.004 198 for VEGFR-2. The differences between different stages had a statistically significance (P < 0.05). Correlation analysis on the mean optical density between beta2-AR and VEGFR-2 had a statistically significance (P < 0. 05).

CONCLUSIONSBeta2-AR and VEGFR-2 may be involved in the occurrence and development of infantile hemangioma.

Child ; Child, Preschool ; Female ; Hemangioma ; metabolism ; Humans ; Infant ; Male ; Receptors, Adrenergic, beta-2 ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; metabolism

OBJECTIVETo investigate the expression and significance of beta-receptor ( p-R) in infantile hemangioma.

METHODSThe expression of beta-R was detected by immunohistochemistry in infantile hemangioma (40 cases), venous malformation (20 cases) and normal skin (10 cases).

RESULTSThe positive expression rate of beta2-R was 70% (28/40) in infantile hemangioma, while no expression of beta2-R in venous malformation and normal skin. Among 28 cases with positive expression of beta2-R, 24 cases were in proliferative phase. The positive expression of beta2-R in infantile hemangioma was significantly higher than that in venous malformation and normal skin tissue. The positive expression of beta2-R in the proliferative hemangioma and non-proliferative hemangioma was also significantly different (P < 0.05).

CONCLUSIONSbeta2-R is specifically expressed in infantile hemangioma, especially in proliferative hemangioma.

Case-Control Studies ; Female ; Hemangioma ; metabolism ; Humans ; Immunohistochemistry ; Infant ; Male ; Receptors, Adrenergic, beta ; metabolism

The α2A adrenoceptors (α2A-ARs) are the most common adrenergic receptor subtype found in the prefrontal cortex (PFC). It is generally accepted that stimulation of postsynaptic α2A-ARs on pyramidal neurons are key to PFC functions, such as working memory. However, the expression of α2A-ARs in interneurons is largely unknown. In the present study using double-labeling immunofluorencence technique, we investigated the expression of α2A-ARs in major types of rat PFC interneurons expressing calcium-binding proteins parvalbumin (PV), calretinin (CR), and calbindin (CB). Our data demonstrated that α2A-ARs are highly expressed in calcium-binding protein immunoreactive interneurons of rat PFC, suggesting that stimulation of α2A-ARs may alter neural networks comprising pyramidal neurons and interneurons, thereby exerting a beneficial effect on PFC cognitive functions. The present study provides the morphological basis for a potential mechanism by which stimulation of α2A-ARs induces cognitive improvement.
Animals ; Calbindin 2 ; metabolism ; Calbindins ; metabolism ; Interneurons ; metabolism ; Parvalbumins ; metabolism ; Prefrontal Cortex ; cytology ; Rats ; Receptors, Adrenergic, alpha-2 ; metabolism

OBJECTIVETo explore the changes on the content of substrate, the activity of correlative enzyme and the mRNA and protein expressions of beta(3)-adrenoceptor and peroxisome proliferator-activated receptor alpha (PPARalpha) in human failing heart.

METHODPapillary muscles from 20 patients with heart failure during mitral valves replacement and 6 control subjects died of non-cardiac accidents were obtained and free fat acid (FFA), lactic acid (LD) and the activity of Na(+)K(+)-ATPase and Ca(2+)Mg(2+)-ATPase, protein and mRNA expressions of beta(3)-adrenergic receptor and PPARalpha were measured.

RESULTIn the failing heart, the contents of fat acid, LD and expression of beta(3)-adrenoceptor mRNA and protein were significantly higher while the activity of Na(+)K(+)-ATPase and Ca(2+)Mg(2+)-ATPase, expressions of PPARalpha at mRNA and protein levels were significantly lower than those in control myocardium.

CONCLUSIONMetabolic remodeling (upregulation of beta(3)-adrenoceptor and downregulation of PPARalpha) might contribute to the pathophysiology of heart failure.

Adult ; Female ; Heart Failure ; metabolism ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; PPAR alpha ; metabolism ; Receptors, Adrenergic, beta-3 ; metabolism

To study the changes in every part of the beta-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups: IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1+, 2+, 3+ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the beta-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group (P < 0.001), while the enzymes were significantly higher in I/R (P < 0.001). The Bmax of beta-AR in IP was much higher than that in I/R (P < 0. 001), but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R (P < 0.05, 0.002 and 0.001, respectively). In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of beta-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA.
Ischemic Preconditioning, Myocardial ; Myocardium/*metabolism ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta/*physiology ; Signal Transduction