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

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

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

PURPOSE: To investigate the effects of brimonidine, an alpha-2-adrenergic agonist, on barrier function in ARPE-19 cells by measuring transepithelial resistance (TER). METHODS: ARPE-19 cells were cultured into a confluent monolayer on a microporous filter. Brimonidine was added to the apical medium, and the barrier function of the cells was evaluated by measuring TER. A subset of cells was treated under hypoxic conditions, and the TER changes observed upon administration of brimonidine were compared to those observed in cells in normoxic conditions. RESULTS: The ARPE cell membrane reached a peak resistance of 29.1+/-7.97 Omega cm2 after four weeks of culture. The TER of the cells treated under normoxic conditions increased with brimonidine treatment; however, the TER of the cells treated under hypoxic conditions did not change following the administration of brimonidine. CONCLUSIONS: Barrier function in ARPE-19 cells increased with brimonidine treatment. Understanding the exact mechanism of this barrier function change requires further investigation.
Adrenergic alpha-Agonists/*pharmacology ; Cell Hypoxia/drug effects/physiology ; Cell Line ; Electric Impedance ; Humans ; Quinoxalines/*pharmacology ; Receptors, Adrenergic, alpha-2/*drug effects ; Retinal Pigment Epithelium/*drug effects/*physiology

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 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

BACKGROUNDThe ADRA2B gene insertion/deletion (I/D) polymorphism is associated with various cardiovascular and metabolic phenotypes. Large (C1) and small (C2) artery compliance, assessed by pulse wave analysis, is considered as sensitive markers or risk factors for cardiovascular disease. Therefore whether the ADRA2B I/D polymorphism is associated with C1 and C2 need to be investigated.

METHODSA total of 227 men and 243 women were enrolled in a Chinese family-based study. C1 and C2 were measured by pulse wave analysis. ADRA2B genotypes were determined by polymerase chain reaction. Statistical methods included generalized estimation equations and quantitative transmission disequilibrium test.

RESULTSThe II (31.9%), ID (46.8%) and DD (21.3%) genotype frequencies were in Hardy-Weinberg equilibrium (P = 0.73). The covariates selected by stepwise regression for C1 and C2 were age, systolic pressure and gender. The population based association analysis showed that C1 and C2 were not associated with ADRA2B genotype both before (C1: P = 0.28; C2: P = 0.27) and after (C1: P = 0.58; C2: P = 0.18) the adjustment. The family-based analyses of 128 informative offspring showed that transmission of the D-allele was not associated with C1 or C2, both before (C1: P = 0.42; C2: P = 0.85) and after (C1: P = 0.31; C2: P = 0.82) the adjustment.

CONCLUSIONThe study do not support that the ADRA2B gene I/D polymorphism has a major gene effect on C1 or C2 in the Chinese population of current sample size.

Adult ; Aged ; Arteries ; physiology ; Blood Pressure ; Compliance ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Adrenergic, alpha-2 ; genetics

The purpose of this study was to investigate the effects of α₂ adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism, so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome (AWS). Adult Sprague-Dawley (SD) male rats were orally administered with 6% aqueous alcohol continuously for 28 d to establish alcohol drinking model, and then stopped drinking to induce AWS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of norepinephrine (NE) in the locus coeruleus and hippocampus of rats. Dexmedetomidine (5, 10, and 20 μg/kg) was intraperitoneally injected respectively when the rats showed significant AWS. In some rats, α₂ adrenergic receptor antagonist yohimbine was injected into hippocampus in advance. The results showed that, compared with the control group, the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking. The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group. Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group, while yohimbine could reverse these effects of dexmedetomidine. These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activating α₂ adrenergic receptor.
Adrenergic alpha-2 Receptor Agonists/therapeutic use* ; Alcoholism/drug therapy* ; Animals ; Dexmedetomidine/therapeutic use* ; Hippocampus/metabolism* ; Male ; Norepinephrine ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-2/metabolism* ; Substance Withdrawal Syndrome/drug therapy* ; Yohimbine/pharmacology*

OBJECTIVE: Dexmedetomidine (DEX), the most specific α ₂-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1α expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxia-inducible factor-1 alpha (HIF-1α) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment. METHODS: We used SMMC-7721 cells, MHCC97-H cells, and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry (VM) and its mechanism. Under normoxic (20% O ₂) and hypoxic (1% O ₂) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them. RESULTS: The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range, and the addition of yohimbine inhibited this effect. DEX could activate HIF-1α/VEGFA pathway, which was further verified by silencing HIF-1α. Consistently, in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression, and enhance the number of VM channels and microvessel density (MVD). CONCLUSION We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas α ₂-adrenergic receptor mediation might be the critical mechanisms.
Animals ; Humans ; Mice ; Adrenergic alpha-2 Receptor Agonists/pharmacology* ; Carcinoma, Hepatocellular ; Cardiovascular Physiological Phenomena ; Dexmedetomidine/pharmacology* ; Hypoxia ; Liver Neoplasms/drug therapy* ; Oxygen ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/genetics* ; Receptors, Adrenergic, alpha-2/metabolism*

BACKGROUND: Tianeptine is an antidepressant drug which is used for treating depression. Interestingly, the tianeptine has shown antinociceptive effects within a variety of nociceptions. The aim of this study is to investigate the antiallodynic effects of tianeptine in neuropathic pain rats and also determine the involvements of serotonergic, alpha-2 adrenergic and adenosine receptors at the spinal level. METHODS: Neuropathic pain was induced by ligation of left lumbar at 5th and 6th spinal nerves in male Sprague-Dawley rats. PE-10 catheters were placed into the thoracolumbar subarachnoid space for drug injections. Mechanical allodynia was evaluated by measuring the withdrawal threshold to von Frey filament when applying on the plantar surface of rats. The effects of intrathecal tianeptine were observed at 15, 30, 60, 90, 120, 150, 180 minutes after delivery. Antagonists for serotonergic (dihydroergocristine), alpha-2 adrenergic (yohimbine) and adenosine (CGS 15943) receptors were intrathecally administered 10 minutes prior to tianeptine in order to evaluate the involvement of both receptors. RESULTS: Intrathecal tianeptine increased dose-dependently at the withdrawal threshold in the ligated paw. Pretreatment with intrathecal dihydroergocristine, yohimbine and CGS 15943 antagonized the antiallodynic effects of tianeptine. CONCLUSIONS: These results suggested that intrathecal tianeptine attenuates the spinal nerve ligation induced tactile allodynia. Serotonergic, alpha-2 adrenergic and adenosine receptors are all involved in the antiallodynic effects of tianeptine at the spinal level.
Adenosine ; Animals ; Catheters ; Depression ; Dihydroergocristine ; Humans ; Hyperalgesia ; Ligation ; Male ; Neuralgia* ; Nociception ; Rats* ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-2 ; Receptors, Purinergic P1 ; Spinal Nerves ; Subarachnoid Space ; Yohimbine