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

This study was designed to explore the innervation of autonomic nervous system and the distribution of receptors on pacemaker cell membrane in guinea pig left ventricular outflow tract (aortic vestibule). By using conventional intracellular microelectrode technique to record action potentials, autonomic neurotransmitters and antagonists were used to investigate the electrophysiological features and regularities of spontaneous activity of left ventricular outflow tract cells. Electrophysiological parameters examined were: maximal diastolic potential (MDP), amplitude of action potential (APA), maximal rate of depolarization (V(max)), velocity of diastolic depolarization (VDD), rate of pacemaker firing (RPF), 50% and 90% of duration of action potential (APD(50) and APD(90)). The results are listed below: (1) Perfusion with 100 mumol/L isoprenaline (Iso) resulted in a significant increase in V(max) (P <0.05), VDD, RPF, and APA (P <0.01), a notable decrease in MDP (P<0.05), and also a marked shortening in APD(50) (P<0.01). Pretreatment with Iso (100 mumol/L), propranolol (5 mumol/L) significantly decreased RPF and VDD (P<0.01), decreased APA, MDP and V(max) (P<0.01) notably, prolonged APD(50) (P<0.01) and APD(90) (P<0.05) markedly. (2) Application of 100 mumol/L epinephrine (E) resulted in a significant increase in VDD (P<0.05), RPF (P<0.001), V(max) (P<0.05) and APA (P<0.001), and a notable shortening in APD(50) and APD(90) (P<0.05). (3) Perfusion with 100 mumol/L norepinephrine (NE) led to a significant increase in VDD, RPF, APA and V(max) (P<0.05), and a marked shortening in APD(50) (P<0.05). Pretreatment with NE (100 mumol/L), phentolamine (100 mumol/L) significantly decreased RPF and VDD, MDP and APA (P<0.01), decreased V(max) notably (P<0.05), prolonged APD(50) and APD(90) markedly (P<0.01). (4) During perfusion with 10 mmol/L acetylcholine (ACh), VDD and RPF slowed down notably (P<0.05), APA decreased significantly (P<0.001), V(max) slowed down notably (P<0.01), APD50 shortened markedly (P<0.05), Atropine (10 mmol/L) antagonized the effects of ACh (10 mumol/L) on APD(50) (P<0.05). These results suggest that there are probably alpha-adrenergic receptor (alpha-AR), beta-adrenergic receptor (beta-AR) and muscarinic receptor (MR) on pacemaker cell membrane of left ventricular outflow tract in guinea pig. The spontaneous activities of left ventricular outflow tract cells are likely regulated by sympathetic and parasympathetic nerves.
Action Potentials ; drug effects ; Animals ; Aorta, Thoracic ; cytology ; physiology ; Electrophysiological Phenomena ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Male ; Microelectrodes ; Neurotransmitter Agents ; physiology ; Receptors, Adrenergic, alpha ; physiology ; Receptors, Adrenergic, beta ; physiology ; Receptors, Muscarinic ; physiology ; Ventricular Function, Left ; physiology

Recent reports suggest that the responses of the detrusor muscle to the hypogastric nerve stimulation and some autonomic drugs may not be identical among various species. In this study, the responses of the isolated detrusor muscle strips of the Amyda Japonica and the rabbit to catecholamines were compared, and the type of the adrenergic-receptors was investigated. The results obtained were as follows : 1. Catecholamines (norepinephrine and epinephrine) evoked only contraction in the isolated detrusor muscle of the Amyda Japonica and relaxation in the preparation of the rabbit. 2. The contraction-response in the Amyda Japonica was blocked in the presence of regitine, an adrenergic alpha-receptor blocking agent. 3. The relaxation-response in the rabbit was abolished by pre-treatment with propranolol, an adrenergic beta-receptor blocking agent. 4. Acetylcholine elicited contraction in both of the isolated detrusor muscle strips of the Amyda japonica and the rabbit, and the response was completely blocked in the presence of atropine. 5. The results described above suggest that catecholamines exert excitatory effect on the detrusor muscle of the Amyda japonica as it contains adrenergic alpha-receptors and inhibitory effect on the same preparation of the rabbit as it contains the adrenergic beta-receptors. Key Word : amyda japonica,alpha receptor, beta receptor.
Acetylcholine ; Atropine ; Autonomic Agents* ; Catecholamines ; Phentolamine ; Propranolol ; Receptors, Adrenergic, alpha ; Receptors, Adrenergic, beta ; Relaxation

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

BACKGROUND: Spinal zaprinast, phospodiesterase inhibitor, has been shown to have an antinociception through an increase of cGMP. The aim of this study was to examine the role of spinal adrenergic and cholinergic receptors on the antinociceptive action of intrathecal zaprinast. METHODS: Rats were implanted with lumbar intrathecal catheters. After formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. After observing the effect of intrathecal zaprinast, antagonism of intrathecal prazosin, yohimbine, atropine and mecamylamine for the effect of zaprinast were evaluated. RESULTS: Intrathecal zaprinast produced a dose-dependent suppression of formalin-induced flinches in both phases of the formalin test. Intrathecal prazosin reversed the antinociception of zaprinast in phase 2, but not phase 1. Intrathecal yohimbine reversed the antinociception of zaprinast in both phases. Neither atropine nor mecamylamine reversed the antinocicetive action of zaprinast. CONCLUSIONS: Intrathecal zaprinast is against the nociceptive state evoked by formalin stimulus. Alpha 2 or alpha 1 adrenergic receptor, but not cholinergic receptors, may be related to the action of zaprinast in the spinal cord.
Animals ; Atropine ; Catheters ; Formaldehyde* ; Mecamylamine ; Pain Measurement* ; Prazosin ; Rats* ; Receptors, Adrenergic, alpha-1 ; Receptors, Cholinergic* ; Spinal Cord ; Yohimbine

The relaxation of the corpus cavernosum smooth muscle, which is main process in penile erection, is controlled by nerves that release cholinergic and nonadrenergic-noncholinergic neurotransmitters as well as vascular endothelium derived relaxing factor(EDRF). But the adrenergically-induced tone maintains the penis in flaccid state. In order to define the physiological role of adrenergic neurotransmission in the local control of penile erection we studied the distribution of alpha adrenergic receptor subtypes and their pharmacological potency in human and rabbit corpus cavernosum tissue. In this study we used yohimbine as the alpha-2 antagonist, which is known to have beneficial therapeutic effect for organic impotence, to assess its neuropharmacological mechanism in the treatment of erectile dysfunction. The alpha-1 : alpha-2 receptor potency was approximately 7.4:1 and 2.2:1 in human and rabbit tissue respectively. These results indicate that the predominant alpha adrenergic receptor is alpha-1 type and alpha-2 receptor antagonist, yohimbine, can not play a main role on the local control of penile erection because of its low receptor potency especially in human corpus cavernosum tissue. It remains possible that yohimbine partially antagonizes the postsynaptic alpha-1 mediated effect or activation of central sympathetic pathway is necessary for the therapeutic effect of yohimbine in human.
Endothelium, Vascular ; Erectile Dysfunction ; Humans* ; Male ; Muscle, Smooth ; Neurotransmitter Agents ; Penile Erection ; Penis ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha* ; Relaxation ; Synaptic Transmission ; Yohimbine

The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.
Acetylcholine ; Arteries ; Autonomic Nervous System ; Cholinergic Neurons ; Homeostasis ; Humans ; Immune System ; Inflammation ; Kidney Diseases ; Kidney ; Macrophages ; Nervous System ; Neurotransmitter Agents ; Norepinephrine ; Optogenetics ; Physiology ; Receptors, Adrenergic ; Receptors, Nicotinic ; Reperfusion Injury ; Spleen ; Sympathectomy ; Sympathetic Nervous System ; T-Lymphocytes ; Ultrasonography ; Vagus Nerve ; Vagus Nerve Stimulation

<b>OBJECTIVEb>To study the interactions between Ligusticum chuanxiong Hort extract and cardiac muscle membrane receptors.

<b>METHODb>The 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.

<b>RESULTb>Water 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.

<b>CONCLUSIONb>It 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

BACKGROUND: Intrathecal gabapentin is effective on nociceptive states evoked by tissue injury. In addition, gabapentin interacts synergistically with clonidine at the spinal level, suggesting that a mechanism of gabapentin may be related to spinal adrenoceptors. However, it has not been established whether this drug is associated with cholinergic receptors. The aim of this study was to examine the role of spinal adrenergic and cholinergic receptors on the antinociceptive action of intrathecal gabapentin. METHODS: Rats were implanted with lumbar intrathecal catheters. For a nociceptive test, 50nl of 5% formalin solution was injected into the hindpaw. The effect of intrathecal gabapentin, administered 10 min before the formalin injection, was assessed. Next, antagonistic effects of intrathecal prazosin, yohimbine, atropine and mecamylamine for the action of intrathecal gabapentin were evaluated. RESULTS: Formalin injection caused a biphasic incidence of flinching of the injected paw. Intrathecal gabapentin produced a dose-dependent suppression of only the phase 2 flinching response in the formalin test. Intrathecal atropine, but not prazosin, yohimbine nor mecamylamine, reversed the antinociception of intrathecal gabapentin. CONCLUSIONS: The antinociceptive effect of intrathecal gabapentin on facilitated states may be mediated through the muscarinic receptor but by neither the nicotinic receptor nor the adrenergic receptor at the spinal level.
Animals ; Atropine ; Catheters ; Cholinergic Antagonists* ; Clonidine ; Formaldehyde ; Incidence ; Mecamylamine ; Nociception ; Pain Measurement ; Prazosin ; Rats ; Receptors, Adrenergic ; Receptors, Cholinergic ; Receptors, Muscarinic ; Receptors, Nicotinic ; Spinal Cord ; Yohimbine

<b>OBJECTIVEb>To 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.

<b>METHODSb>Synthetic 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.

<b>RESULTSb>The 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%.

<b>CONCLUSIONSb>Autoantibodies 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