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

OBJECTIVEPostural tachycardia syndrome (POTS) is one of the major causes of orthostatic intolerance in children. We systematically reviewed the pathogenesis and the progress of individualized treatment for POTS in children.

DATA SOURCESThe data analyzed in this review are mainly from articles included in PubMed and EMBASE.

STUDY SELECTIONThe original articles and critical reviews about POTS were selected for this review.

RESULTSStudies have shown that POTS might be related to several factors including hypovolemia, high catecholamine status, abnormal local vascular tension, and decreased skeletal muscle pump activity. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta-adrenoreceptor blockers, and alpha-adrenoreceptor agonists. However, reports about the effectiveness of various treatments are diverse. By analyzing the patient's physiological indexes and biomarkers before the treatment, the efficacy of medication could be well predicted.

CONCLUSIONSThe pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. Biomarker-directed individualized treatment is an important strategy for the management of POTS children.

Adrenergic alpha-Agonists ; therapeutic use ; Adrenergic beta-Antagonists ; therapeutic use ; Catecholamines ; metabolism ; Humans ; Postural Orthostatic Tachycardia Syndrome ; drug therapy ; metabolism ; pathology ; therapy

OBJECTIVETo demonstrate the inhibitory effect of kappa-opioid receptor activation by U50488H on hypertrophy induced by NE in cultured neonatal rat cardiac myocytes and compare its effect with that of prazosin and propranolol.

METHODSThe cellular proliferation was determined with crystal violet staining. The protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-lencine incorporation method.

RESULTS(1) NE significantly induced the increase of protein content, [3H]-leucine incorporation and cell size without a concomitant increase in cell number in low serum medium. OThese responses were partially suppressed by prazosin or propranolol alone and completely abolished by both in combination. U50488H significantly inhibited the NE-induced increase of protein content, [3H]-leucine incorporation and cell size. The inhibitory effects of U50488H on NE-induced cardiac hypertrophy were greater than either prazosin or propranolol, but comparable to combination of both.

CONCLUSIONNE, acting via both alpha1- and beta-adrenergic pathway, stimulates myocyte hypertrophy. Stimulating kappa-opioid receptor significantly inhibits NE-induced cardiac hypertrophy, which may be related with alpha1- and beta1-adrenergic pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Adrenergic alpha-1 Receptor Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Animals, Newborn ; Cardiomegaly ; chemically induced ; pathology ; prevention & control ; Cell Enlargement ; drug effects ; Cells, Cultured ; Female ; Male ; Myocytes, Cardiac ; cytology ; Norepinephrine ; Prazosin ; pharmacology ; Propranolol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

PURPOSE: To investigate the role of beta-adrenergic receptors, and the relevance of NO-mediated & calcium channel-mediated signal transduction in seminal vesicle contractions. MATERIALS AND METHODS: Rabbit seminal vesicle strip preparations were applied to an organ bath system under standard condition. Smooth muscle contractions were induced by alpha and/or beta-adrenergic agonists (norepinephrine, phenylephrine, isoproterenol), and blocked by alpha (prazosin) and/or beta (propranolol)-blocker, an NO donor (sodium nitroprusside) and calcium channel blocker (verapamil). The contractility of the smooth muscle was measured by EC50. RESULTS: Norepinephrine, phenylephrine and isoproterenol produced a sudden increase in the contractions of the smooth muscle. The order of the adrenergic agonists in relation to increases in the contractility was norepinephrine>phenylephrine>isoproterenol. The contractions induced by norepinephrine and phenylephrine were partially blocked by prazosin, and those by isoproterenol were completely blocked by propranolol. The contraction induced by norepinephrine was partially blocked by sodium nitroprusside and verapamil, in dose dependant manners. CONCLUSIONS: Seminal vesicle contractions are mediated mostly by alpha-adrenergic receptors, and seem to be partly mediated by beta-adrenergic receptors. The contractility of seminal vesicle seems to be partly regulated by the NO-cGMP-cascade and calcium channel mediated signal transduction.
Adrenergic Agonists ; Adrenergic beta-Agonists ; Baths ; Calcium ; Calcium Channels ; Humans ; Isoproterenol ; Muscle, Smooth ; Nitroprusside ; Norepinephrine ; Phenylephrine ; Prazosin ; Propranolol ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha ; Receptors, Adrenergic, beta ; Seminal Vesicles* ; Signal Transduction ; Tissue Donors ; Verapamil

PURPOSE: Fentanyl was reported to inhibit the alpha1-adrenoceptor agonist-induced contraction. The goal of this in vitro study was to identify the alpha1-adrenoceptor subtype primarily involved in the fentanyl-induced attenuation of phenylephrine-induced contraction in isolated endothelium-denuded rat aorta. MATERIALS AND METHODS: Aortic rings were suspended in order to record isometric tension. Concentration-response curves for phenylephrine (10-9 to 10-5 M) were generated in the presence or absence of one of the following drugs: fentanyl (3x10-7, 10-6, 3x10-6 M), 5-methylurapidil (3x10-8, 10-7, 3x10-7 M), chloroethylclonidine (10-5 M) and BMY 7378 (3x10-9, 10-8, 3x10-8 M). Phenylephrine concentration-response curves were generated in the presence or absence of fentanyl in rings pretreated with either 3x10-9 M prazosin, 10-9 M 5-methylurapidil or 3x10-9 M BMY 7378. RESULTS: Fentanyl (10-6, 3x10-6 M) attenuated phenylephrine-induced contraction in the rat aorta. 5-Methylurapidil and BMY 7378 produced a parallel rightward shift in the phenylephrine concentration-response curve. The pA2 values for 5-methylurapidil and BMY 7378 were estimated to be 7.71 +/- 0.15 and 8.99 +/- 0.24, respectively. Fentanyl (10-6 M) attenuated phenylephrine-induced contraction in rings pretreated with 10-9 M 5-methylurapidil, but did not alter the rings when pretreated with 3x10-9 M BMY 7378. Pretreatment of the rings with chloroethylclonidine showed a 72.9 +/- 2.3% reduction in phenylephrine-induced maximal contraction. CONCLUSION: The results suggest that fentanyl attenuates phenylephrine-induced contraction by inhibiting the pathway involved in the alpha1D-adrenoceptor-mediated contraction of the rat aorta.
Adrenergic alpha-Agonists/*pharmacology ; Adrenergic alpha-Antagonists/*pharmacology ; Animals ; Aorta/*drug effects ; Clonidine/analogs & derivatives/pharmacology ; Fentanyl/*pharmacology ; Male ; Phenylephrine/*pharmacology ; Piperazines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/*drug effects

Urinary incontinence is an important lower urinary tract symptom that negatively affects the quality of life. Urgency incontinence (UI) is urine loss accompanied by urgency, which is the chief complaint of overactive bladder (OAB) syndrome. OAB is defined as urgency, with or without UI, usually with frequency and nocturia. In contrast, stress urinary incontinence (SUI) involves involuntary urine leakage caused by a sudden increase in abdominal pressure. Treatment for urinary incontinence depends on the type of incontinence, the severity, and the underlying causes. Treatment options fall into four broad categories: lifestyle intervention, bladder retraining and/or pelvic floor muscle training, pharmacotherapy, and surgery. Pharmacotherapy is often the first-line therapy for OAB/UI, either alone or as an adjunct to various nonpharmacological therapies. Effectiveness of anticholinergic drugs for OAB/UI has been assessed in various observational and randomized controlled trials. Despite their side effects, anticholinergics are the first-line agents for UI. Tricyclic antidepressants have complex pharmacological actions such as anticholinergic, alpha adrenergic, antihistaminic, and local anesthetic properties. Recently approved anticholinergics, solifenacin and darifenacin, are selective M3 antagonists that may have tolerable side effects. Transdermal oxybutynin may offer comparable efficacy with oral formulation but lower side effects. In the absence of an effective and well tolerated drug for SUI, pharmacological therapy for this condition has remained in the off-label prescription of some products, particularly estrogens and alpha-adrenergic agonists. Duloxetine is the drug of choice specifically aimed at SUI. This article outlines the current state and future development in pharmacological therapy for urinary incontinence.
Adrenergic alpha-Agonists ; Antidepressive Agents, Tricyclic ; Cholinergic Antagonists ; Drug Therapy ; Duloxetine Hydrochloride ; Estrogens ; Life Style ; Nocturia ; Pelvic Floor ; Prescriptions ; Quality of Life ; Solifenacin Succinate ; Urinary Bladder ; Urinary Bladder, Overactive ; Urinary Incontinence* ; Urinary Tract

In acupuncture practice of animals, preanesthetics sometimes are needed. The purpose of this study was to select the ideal chemical restraint at acupuncture for gastric motility. Nine healthy mixed breed dogs weighed 10-21 kg and aged 1-3 years old were used in this study. Two EMG surface electrodes were placed between the seromuscular and the mucosal layer of pylorus. Twenty minutes after feeding normal gastric motility was recorded for 60 minutes using physiograph (Narco-Biosystem). Then preanesthetic treated-gastric motility was observed for 30 minutes. Preanesthetics used were xylazine, diazepam, and acepromazine. Acupuncture needles were inserted to BL-21 (Wei-Yu) acupoint, and then changes of gastric motility were recorded for 60 minutes. The gastric motility following xylazine administration (1 mg/kg, IV) was markedly decreased. BL-21 (Wei-Yu) acupoints stimulation did not alter xylazine-induced depression of gastric motility. The diazepam (1 mg/kg IV) treated-gastric motility was increased mildly 20 minutes after drug administration. BL-21 (Wei-Yu) acupoint stimulation after diazepam administration enhanced gastric motility significantly. The gastric motility following acepromazine (0.3 mg/kg, IM) administration was not changed compared with normal gastric motility. Application of traditional acupuncture at BL-21 (Wei-Yu) significantly increased the gastric motility. Based on these results, acepromazine and diazepam could be acceptable chemical restraints for acupuncture therapy of gastric motility, but xylazine couldn't be.
Acepromazine ; Acupuncture/*standards ; *Acupuncture Points ; Adjuvants, Anesthesia ; Adrenergic alpha-Agonists ; Animals ; Antipsychotic Agents ; Atropine ; Diazepam ; Dogs/*physiology ; Dopamine Antagonists ; Electromyography/veterinary ; Gastrointestinal Motility/drug effects/*physiology ; Hypnotics and Sedatives ; Metoclopramide ; Parasympatholytics ; Preanesthetic Medication/standards/*veterinary ; Xylazine

Objective: To explore the protective effects of dexmedetomidine (Dex) against high glucose-induced epithelial-mesenchymal transition in HK-2 cells and relevant mechanisms. Methods: HK-2 cells were exposed to either glucose or glucose+Dex for 6 h. The production of ROS, morphology of HK-2 cells, and cell cycle were detected. Moreover, the expression of AKT, p-AKT, ERK, p-ERK, PI3K, E-Cadherin, Claudin-1, and α-SMA were determined and compared between HK-2 cells exposed to glucose and those exposed to both glucose and Dex with or without PI3K/AKT pathway inhibitor LY294002 and ERK pathway inhibitor U0126. Results: Compared with HK-2 cells exposed to high level of glucose, the HK-2 cells exposed to both high level of glucose and Dex showed: (1) lower level of ROS production; (2) cell morphology was complete; (3) more cells in G1 phase; (4) lower expression of p-AKT, p-ERK and α-SMA, higher expression of E-Cadherin and Claudin-1. PI3K/AKT inhibitor LY294002 and ERK inhibitor U0126 decreased the expression of p-AKT, p-ERK and α-SMA, and increased the expression of E-Cadherin and Claudin-1. Conclusion Dex can attenuate high glucose-induced HK-2 epithelial-mesenchymal transition by inhibiting AKT and ERK.
Adrenergic alpha-2 Receptor Agonists ; pharmacology ; Cell Line ; Dexmedetomidine ; pharmacology ; Epithelial-Mesenchymal Transition ; drug effects ; Glucose ; metabolism ; Humans ; MAP Kinase Signaling System ; drug effects ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; Signal Transduction ; drug effects

This study was designed to determine the effect of electrical field stimulation (EFS) and adrenergic agonist on the contractility of vasectomized prostatic and epididymal segments at postvasectomized 2, 5 and 10 weeks, and to observe innervation changes of the vas deferens after vasectomy. The contractile response was recorded on a polygraph via force transducer and expressed as the g tension per 100 mg tissue. And we reviewed histopathologic sections stained with S-100 protein by light microscopy. The results were as follows: 1. In control groups, contractile responses of prostatic and epididymal segments to EFS (4, 8, 16, 32 &64 Hz) were gradually increased by increasing frequencies. But contractile responses of vasectomized epididymal segments to all frequencies of EFS declined. Contractile responses of vasectomized prostatic segments were significantly greater than that of vasectomized epididymal segments (p<0.05). 2. Contractile responses of epididymal segments to phenylephrine hydrochloride 0.00001M were significantly greater than that of prostatic segments (p<0.05). Contractile responses of prostatic segments were tend to decline. In epididymal segments, contractile response of post-vasectomized 5 weeks group was significantly greater than that of control and post-vasectomized 2 weeks groups (p<0.05). 3. In control and vasectomized prostatic segment, nerve bundles were strongly positive and intact histopathologically for the S-100 protein immunohistochemical stain. In epididymal segment, nerve bundles were intact in control group. However, vacuolar degeneration tend to be gradually increased and stained weakly by increasing duration in vasectomized epididymal segment. These results suggest that the progression of degenerative change of adrenergic innervation after vasectomy may play an important role in progressively decreasing contractility of the vas deferens after vasectomy.
Adrenergic Agonists ; Adrenergic alpha-Agonists* ; Animals ; Microscopy ; Phenylephrine ; Rats* ; S100 Proteins ; Transducers ; Vas Deferens* ; Vasectomy*

The basic action mechanism of sodium-glucose cotransporter 2 (SGLT2) inhibitor is to lower the glucose burden by excreting the glucose filtered by the kidney into the urine. Although SGLT2 inhibitors are primarily indicated as glucose-lowering agents, they have a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. That might be why SGLT2 inhibition causes spill-over of sodium and glucose beyond the proximal tubule, triggering dynamic and reversible realignment of energy metabolism, renal filtration, and plasma volume. A better understanding of SGLT2 inhibition in the kidney and the entire body will lead to more benefits in people with and without diabetes.
Adiposity ; Diabetes Mellitus ; Energy Metabolism ; Filtration ; Glucose ; Homeostasis ; Kidney ; Molecular Mechanisms of Pharmacological Action ; Plasma Volume ; Sodium