BACKGROUND: The effect of spinal adrenergic and cholinergic receptors on the anti-nociceptive effect of intrathecal ginsenosides was determined in a rat postoperative pain model. METHODS: Catheters were placed into the intrathecal space of male Sprague-Dawley rats. Postoperative pain was evoked by an incision to the plantar surface of a hind paw. Withdrawal thresholds was used as a nociceptive parameter and was measured with a von Frey filament. After observing the effect of intrathecal ginsenosides, an alpha-1 adrenergic receptor antagonist (prazosin), an alpha-2 adrenergic receptor antagonist (yohimbine), a muscarinic acetylcholine receptor antagonist (atropine), and a nicotinic acetylcholine receptor antagonist (mecamylamine) were given 10 min before administration of the ginsenosides to analyze the contribution of spinal adrenergic and cholinergic receptors on the antinociceptive effect of ginsenosides. RESULTS: Paw incision decreased withdrawal threshold in incised site of paw, but no change of withdrawal threshold was not seen in non-incised site. The intrathecal ginsenosides increased withdrawal threshold of the incised paw in a dose-dependent manner. Pre-treatment with both prazosin and intrathecal yohimbine antagonized the anti-nociceptive effect of the ginsenosides. However, pre-treatments with atropine or mecamylamine had any effect on the antinociceptive activity of ginsenosides. CONCLUSIONS: Intrathecal ginsenosides are effective in attenuation of postoperative pain induced in the rat model. Anti-nociceptive action of ginsenosides is partially mediated by spinal adrenergic receptors, but does not appear to be related to spinal cholinergic receptors.
Animals ; Atropine ; Catheters ; Ginsenosides ; Humans ; Male ; Mecamylamine ; Pain, Postoperative ; Prazosin ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha-1 ; Receptors, Adrenergic, alpha-2 ; Receptors, Cholinergic ; Receptors, Muscarinic ; Receptors, Nicotinic ; Spinal Cord ; Yohimbine

OBJECTIVETo determine whether autoantibodies against the cardiac G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors are related to patients with primary hypertension.

METHODSSynthetic peptides corresponding to amino acid sequences of the second extracellular loops of the beta 2- and alpha 1-adrenergic and AT1 receptors were respectively used as antigens to screen sera from patients with hypertensive heart diseases (n = 50) as well as simple hypertension (n = 40) and healthy blood donors (n = 40) using ELISA test.

RESULTSThe positive ratio of autoantibodies against beta 2 and alpha 1 and AT1 receptors in patients with hypertensive heart diseases were significantly higher than patients with simple hypertension and healthy donors. The geometric mean titers of autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors had no difference between the patients with hypertensive heart diseases and the patients with simple hypertension, but the geometric mean titers of two groups were higher than healthy donors. In the patients with hypertensive heart diseases, 81.0% of the patients with autoantibodies against beta 2-adrenergic receptor had autoantibodies against alpha 1-adrenergic receptor and 76.2% had autoantibodies against AT1 receptors. The percent of the autoantibodies against three receptors in patients with hypertensive heart diseases were 52.4%.

CONCLUSIONSAutoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors play an important role in the pathophysiological changes of primary hypertension, and may participate myocardial and vessel remodeling.

Adult ; Aged ; Autoantibodies ; blood ; Female ; Humans ; Hypertension ; immunology ; Male ; Middle Aged ; Receptor, Angiotensin, Type 1 ; immunology ; Receptors, Adrenergic, alpha-1 ; immunology ; Receptors, Adrenergic, beta-2 ; immunology

OBJECTIVETo elucidate the relationship between rat hepatic stellate cells (HSC) and sympathetic neurotransmitter norepinephrine (NE) during liver fibrosis.

METHODSUsing immunofluorescence and RT-PCR, the expressions of a1 and b2-adrenoceptors in activated HSC were detected. Methyl thiazolyl tetrazolium (MTT) was adopted to investigate the effect of NE on the proliferation of HSC. Meanwhile, the expressions of collagen-1, transforming growth factor beta (TGFb) and smooth muscle a-actin (a-SMA) in NE-stimulated HSC were detected by RT-PCR. The contents of NE in HSC were determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD).

RESULTSThe a1 and b2-adrenoceptors were expressed in HSC. NE markedly stimulated the proliferation of HSC in a concentration-dependent manner (F = 140.464, P less than 0.05). NE induced the mRNA expressions of collagen-1, TGFb and a-SMA in HSC (t= -4.160; t= -8.763; t= -17.651, P less than 0.05). HSC were synthesizing and releasing NE, especially when stimulated with platelet-derived growth factor (PDGF) (10 ng/ml) (t= -32.907, P less than 0.05).

CONCLUSIONOur findings show that HSC are direct targets of NE and HSC are hepatic neuroglial cells that produce and respond to sympathetic neurotransmitter norepinephrine, suggesting that interrupting sympathetic nervous system signaling may be useful in the treatment of liver fibrosis.

Actins ; metabolism ; Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Hepatic Stellate Cells ; drug effects ; metabolism ; Liver Cirrhosis ; Norepinephrine ; pharmacology ; Rats ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Adrenergic, beta-2 ; metabolism ; Transforming Growth Factor beta ; metabolism

OBJECTIVETo evaluate the effect of carvedilol on the cardiac function and autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in patients with chronic heart failure (CHF).

METHODS54 patients with CHF were divided randomly into two groups, one was regular treatment group treated with ACE inhibitor, digoxin and diuretic, another was carvedilol treatment group treated with carvedilol on the basis of above regular treatment. All the patients were followed up for six months and measured the changes of cardiac function and three autoantibodies by echocardiography and enzyme-linked immunosorbent assay (ELISA) respectively.

RESULTS(1) After carvedilol treatment, LVEDD and LVESD (57.50 +/- 7.29) mm and (43.17 +/- 8.27) mm were smaller than that in regular treatment group [(64.09 +/- 7.40) mm and (52.93 +/- 8.35) mm], and LVEF [(50.41 +/- 10.91)%] was higher than that [(41.70 +/- 7.45)%] in regular treatment group (P < 0.01). (2) After carvedilol treatment, the positive ratios and average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors all decreased significantly compared with that of pre-treatment (P < 0.05). The positive ratios of autoantibodies against the three receptors in carvedilol treatment group were lower than those in regular treatment group (P < 0.05). The average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in carvedilol treatment group (1:72.44, 1:61.66 and 1:67.30) were lower than those in regular treatment group (1:113.24, 1:110.66 and 1:113.24), P < 0.05.

CONCLUSIONSCarvedilol decreased positive ratio and average titer of autoantibodies against the beta(1), beta(2) and alpha(1) receptors accompanied with the obvious improvement of cardiac function though the blockade of beta(1), beta(2) and alpha(1) receptors. It suggests that the autoantibodies might be involved in the process of pathophysiology and development of CHF. Carvedilol can inhibit this process.

Adult ; Aged ; Autoantibodies ; blood ; Carbazoles ; therapeutic use ; Female ; Follow-Up Studies ; Heart Failure ; drug therapy ; immunology ; physiopathology ; Humans ; Male ; Middle Aged ; Propanolamines ; therapeutic use ; Receptors, Adrenergic, alpha-1 ; immunology ; Receptors, Adrenergic, beta-1 ; immunology ; Receptors, Adrenergic, beta-2 ; immunology ; Young Adult

The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology.
Animals ; Diabetes Mellitus, Type 2/drug therapy/*metabolism ; GTP-Binding Protein alpha Subunits/genetics/*metabolism ; Humans ; Insulin-Secreting Cells/metabolism ; Obesity/drug therapy/*metabolism ; Receptor, Melatonin, MT2/genetics/*metabolism ; Receptors, Adrenergic, alpha-1/genetics/*metabolism ; Receptors, Prostaglandin/genetics/*metabolism

PURPOSE: The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system of veins and arteries, and the blood vessels of the cavernous body are innnervated by the autonomic nervous system. The purpose of this study was to determine the effect of an adrenergic agonist on the lumen width of the nasolacrimal drainage system. METHODS: Dacryocystography was performed on 35 patients with only epiphora and not nasolacrimal duct obstruction. The anteroposterior (AP) diameters and the oblque diameters of the nasolacrimal ducts were measured. Next, 18 patients were infused with 0.5 ml Alphagan-P(R) (alpha-2 adrenergic receptor agonist), 17 patients were infused with 0.5 ml DL methylephedrine hydrochloride (alpha-1 and alpha-2 adrenergic receptor agonist), and dacryocystography was performed again to determine the change in the lumen width of the nasolacrimal drainage system. RESULTS: The alpha-adrenergics caused a significant increase in the lumen width of the nasolacrimal drainage system, and the changes were more pronounced in the nasolacrimal duct than in the lacrimal sac. Although the nasolacrimal duct widening was more notable in the Alphagan-P(R) infusion group than the DL methylephedrine hydrochloride infusion group, there was no significant statistical difference. Patients' subjective symptoms improved in both groups. CONCLUSIONS: The alpha-adrenergics constrict the blood vessels of the cavernous body, leading to the increase in the lumen width of the nasolacrimal drainage system. This effect was more significant in the Alphagan-P(R) infusion group. In conclusion, infusion of alpha-adrenergics in patients with functional nasolacrimal duct obstruction can be considered as an alternative to surgical management.
Adrenergic Agonists ; Arteries ; Autonomic Nervous System ; Blood Vessels ; Caves ; Drainage ; Ephedrine ; Humans ; Lacrimal Apparatus Diseases ; Nasolacrimal Duct ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha-2 ; Veins

mRNAs of alpha-adrenoceptor (&alpha;-AR) subtypes are found in neurons in dorsal root ganglion (DRG) and change after peripheral nerve injury. In this study, the distribution of &alpha;-AR subtype proteins was studied in L5 DRG of normal rats and rats with chronic constriction injury of sciatic nerve (CCI). Using immunofluorescence technique, it was found that &alpha;1A-, &alpha;1B-, and &alpha;2A-AR proteins were expressed in large, medium, and small size neurons in normal DRG, and significantly increased in all size neurons 14 days after CCI. &alpha;1D- and &alpha;2C-AR was also expressed in all size neurons in normal DRG. However, &alpha;1D-AR was significantly increased and &alpha;2C-AR was decreased in small size neurons 14 days post CCI. &alpha;2B-AR neurons were not detectable in normal and CCI DRG. Co-expression of &alpha;1A- and &alpha;2A-AR in the same neuron was observed in normal DRG and increased post CCI. Collectively, these results indicated that there is distinct distribution of &alpha;-AR subtypes in DRG neurons, and the distribution and levels of expression of &alpha;-AR subtypes change differently after CCI. The up-regulation of &alpha;-AR subtypes in DRG neurons may play an important role in the process of generating and transmitting neuropathic pain.
Animals ; Cell Size ; Chronic Disease ; Constriction, Pathologic ; Fluorescent Antibody Technique ; Ganglia, Spinal ; metabolism ; pathology ; Male ; Microscopy, Confocal ; Neurons ; metabolism ; pathology ; Pain Measurement ; methods ; Pain Threshold ; Protein Isoforms ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Adrenergic, alpha-2 ; metabolism ; Sciatic Nerve ; injuries ; surgery

alpha1-adrenoceptor antagonists are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia, while their adverse effects on sexual function are reported frequently in recent years, especially the induction of ejaculatory dysfunction. This review presents the distribution of alpha 1-adrenoceptors in the male genital system and the relationship of alpha1-adrenoceptors with ejaculatory function. It also highlights the interesting phenomenon of ejaculatory dysfunction related to these drugs and its possible mechanism, with the intention to provide some essential clues for further research on this problem as well as some references to safer use of these drugs in clinical settings.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; pharmacology ; Ejaculation ; physiology ; Erectile Dysfunction ; chemically induced ; physiopathology ; Humans ; Male ; Receptors, Adrenergic, alpha-1 ; physiology

Benign prostatic hyperplasia (BPH) is a common senile disease, and its main clinical manifestation is lower urinary tract symptom (LUTS), which has long been afflicting old male patients. Previous study showed that alpha1-receptor in the prostate was involved in the development of LUTS. At present, alpha1-receptor blocker is generally accepted as a choice drug for treating BPH and relieving LUTS. The article reviews the tissue distribution of alpha1-receptor and clinical application of alpha1-receptor blocker.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; pharmacokinetics ; therapeutic use ; Humans ; Male ; Prostatic Hyperplasia ; drug therapy ; Receptors, Adrenergic, alpha-1 ; analysis

OBJECTIVE: This study is to explore the effects on specific bindings between [ 3H]RX821002, alpha-2 adrenergic receptor antagonist and alpha-2 adrenergic receptor in rat brain by G-protein modulation. METHODS: The radioligand binding receptor study was conducted with [ 3H]RX821002, a new alpha-2 adrenergic receptor antagonist, in the presence or absence of Gpp(NH)p and pertussis toxin. RESULTS: The alpha-2 adrenergic receptors were saturated with [ 3H]RX821002 in the fashion of the single binding site. The dissociation constant (Kd) was 0.70+/-0.30 nM, and maximum binding (Bmax) was 599.9+/-283.4 fmol/mg protein. The saturation study showed that the maximum binding (B max ; 668.0+/-50.1 fmol/mg protein) was increased and the dissociation constant (Kd ; 0.61+/-0.14 nM) was decreased significantly in the presence of Gpp (NH)p compared to those (B max ; 559.8+/-81.9 fmol/mg protein, Kd ; 0.87+/-0.14 nM) in the absence of Gpp (NH)p (by paired t-test ; B max, p=0.023, Kd, p=0.005). In the presence of pertussis toxin, the maximum binding (B max ; 617.0+/-58.5 fmol/mg protein) was increased significantly (by paired t-test ; B max, p=0.001) but the issociation constant (Kd ; 0.92+/-0.24 nM) was not decreased compared to those (B max ; 554.1+/-66.1 fmol/mg protein, Kd ; 0.89+/-0.24 nM) in the absence of pertussis toxin. CONCLUSION: These results confirm that the binding profiles between [ 3H]RX821002 and alpha-2 adrenergic receptors be modified by G-protein modulation. This suggests that the drug effects on receptors be influenced by various conditions such as G-protein modulation.
Animals ; Binding Sites ; Brain* ; GTP-Binding Proteins* ; Guanylyl Imidodiphosphate ; Pertussis Toxin ; Rats* ; Receptors, Adrenergic, alpha-2