Abstract:
:Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that develops as a consequence of prolonged hyperglycaemia-induced injury to the long nerves. Apart from pain, PDN is also characterized by morphine hyposensitivity. Intriguingly, in streptozotocin (STZ)-induced diabetic rats exhibiting marked morphine hyposensitivity, dietary administration of the nitric oxide (NO) precursor, L-arginine at 1 g/d, progressively rescued morphine efficacy and potency over an 8-week treatment period. In earlier work, single bolus doses of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde), evoked dose-dependent pain relief in STZ-diabetic rats but the efficacious doses were 3-4 orders of magnitude higher in advanced diabetes than that required in early STZ diabetes. Together, these findings suggested a role for NO in the modulation of μ-opioid (MOP) receptor signalling. Therefore, the present study was designed to assess a role for NO released from PRG150, in modulating MOP receptor function in vitro. Here, we show an absolute requirement for the MOP receptor, but not the δ-opioid (DOP) or the κ-opioid (KOP) receptor, to transduce the cellular effects of PRG150 on forskolin-stimulated cAMP responses in vitro. PRG150 did not interact with the classical naloxone-sensitive binding site of the MOP receptor, and its effects on cAMP responses in HEK-MOP cells were also naloxone-insensitive. Nevertheless, the inhibitory effects of PRG150 on forskolin-stimulated cAMP responses in HEK-MOP cells were dependent upon pertussis toxin (PTX)-sensitive Gi/o proteins as well as membrane lipid rafts and src kinase. Together, our findings implicate a role for NO in modulating MOP receptor function in vivo.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Huang L,Wyse BD,Williams CM,Smith MTdoi
10.1111/1440-1681.13091subject
Has Abstractpub_date
2019-07-01 00:00:00pages
676-685issue
7eissn
0305-1870issn
1440-1681journal_volume
46pub_type
杂志文章abstract::1. This paper reports on the in vitro and in vivo characteristics of a non-peptide vasopressin V1 receptor antagonist 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2( 1H)- quinolinone (OPC-21268). 2. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radio...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01713.x
更新日期:1993-05-01 00:00:00
abstract::1. Visfatin (also known as nicotinamide phosphoribosyltransferase or Nampt) is a novel adipokine associated with metabolic abnormalities in obesity and diabetes. The aim of the present study was to determine whether visfatin levels in the circulation and visfatin expression in fat tissues are altered in Lyon hypertens...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05402.x
更新日期:2010-09-01 00:00:00
abstract::1. The functional innervation of autonomic target tissues occurs early during development, at a time when both the nerves and post-synaptic target tissues are still differentiating. 2. Physiological responses appear soon after the arrival of the first fibres when uptake and release mechanisms within the nerves are alr...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.1999.03092.x
更新日期:1999-08-01 00:00:00
abstract::1. Inhibiting the renin-angiotensin-aldosterone system prevents left ventricular (LV) remodelling after myocardial infarction (MI). 2. The present study was designed to assess the effects of a combination of perindopril and losartan on LV remodelling, cardiac function and serum procollagen type III amino terminal pept...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2009.05143.x
更新日期:2009-07-01 00:00:00
abstract::1. The acute effects of captopril on blood pressure, renin, angiotensin, bradykinin and catecholamines were examined in patients with essential (n = 10, Group 1), accelerated (n = 6, Group 2) and renal hypertension (n = 14, Group 3). 2. Blood pressure showed little change in Group 1, fell significantly in Group 2, wit...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00097.x
更新日期:1980-09-01 00:00:00
abstract::1. Mammalian heart muscle is extremely sensitive to the external calcium concentration. It reacts to alterations of the external calcium concentration with an immediate adaptation of contractile force. 2. In mammalian heart there is a network of large transverse tubules throughout the cell. These structures are regula...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1977.tb02377.x
更新日期:1977-01-01 00:00:00
abstract::1. Indices quantifying blood pressure (BP) and heart rate (HR) variability have been recently developed and may be used to assess the contribution of the autonomic nervous system to cardiovascular fluctuations. 2. Cardiovascular variables were measured in eight conscious mice equipped with a BP telemetric device. Each...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04895.x
更新日期:2008-04-01 00:00:00
abstract::1. The effects of the Class I anti-arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea-pig heart preparations. 2. All the tested drugs inhibited the enzyme activity in a concentration-dependent fashion, exhibiting varying ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01671.x
更新日期:1993-04-01 00:00:00
abstract::1. Whole-cell patch recordings were made from antidromically identified sympathetic preganglionic neurons (SPN) of immature rat spinal cord slices. Bath application of nociceptin (0.1-1 micromol/L) suppressed excitatory postsynaptic potentials (EPSP) and hyperpolarized a population of SPN; these effects were naloxone ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03635.x
更新日期:2002-03-01 00:00:00
abstract::1. The effect of cicletanine, a novel antihypertensive agent with natriuretic activity, on blood pressure and progression of renal failure of 5/6 nephrectomized spontaneously hypertensive rats with salt loading was examined. 2. All nephrectomized rats were randomly assigned to one of four groups and their diet was cha...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03021.x
更新日期:1999-03-01 00:00:00
abstract::1. Adult soft-shelled turtles were exposed to hyperosmotic and dehydration stresses. 2. Acute treatment for 0.5, 1 or 2 h with sodium chloride (3.6%, single intramuscular injection, 2 mL volume) caused depletion of pineal serotonin contents followed by elevation of norepinephrine and epinephrine levels. In addition, i...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01386.x
更新日期:1991-10-01 00:00:00
abstract:OBJECTIVE:Diabetes mellitus is a prevalent endocrine disorder worldwide. Citrulline is an α-amino acid, which is abundant in watermelon, and a precursor of arginine and nitric oxide. Decreased bioavailability of nitric oxide is associated with insulin resistance. The present systematic review focused on the existing ev...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.13190
更新日期:2020-02-01 00:00:00
abstract::Cardiotoxin (CTX) III, a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. In the present study, we investigated the mechanisms underlying the anticancer activity of CTX III in human leukaemia (HL-60 cells). Cardiotoxin III activated the en...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04968.x
更新日期:2008-09-01 00:00:00
abstract::Aerobic glycolysis plays a crucial role in cancer progression. Ketamine is often used for cancer pain relief in clinical settings. Moreover, ketamine inhibits proliferation and induces apoptosis in many cancer cell types. However, the anti-tumour mechanism of ketamine is still poorly understood. In the present study, ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13248
更新日期:2020-05-01 00:00:00
abstract::1. The aim of this study was to evaluate the role of endothelium in mediating the response to acetylcholine in the thoracic aorta and coronary vessels of rats exposed to cigarette smoking. Total serum cholesterol was measured at the beginning and end of the experiment. 2. The relaxation response to acetylcholine was s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1995.tb02031.x
更新日期:1995-06-01 00:00:00
abstract::1. The development of microneurography, in which an insulated tungsten microelectrode is inserted into an accessible peripheral or cranial nerve in awake human subjects, has allowed detailed analyses of the signalling capacities of single mechanoreceptive afferents from the skin, muscles and joints. For example, we kn...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2005.04143.x
更新日期:2005-01-01 00:00:00
abstract::The anti-acetylcholinesterase (AChEase) activity of 15 opioids, namely morphine, nalorphine, oxymorphone, naloxone, naltrexone, N-methylnaloxone, levorphanol, levallophan, dextrorphan, dextrallophan, levo-methadone, dextro-methadone, pethidine, leu-enkephalin and U-50,488H was investigated. Among the opioids, the morp...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00330.x
更新日期:1986-02-01 00:00:00
abstract::1. The contractile effects of tea polyphenols (TP) and its four principle catechins, namely (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG), on rat aorta contractility were investigated using the isometric tension recording technique. 2. At co...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03796.x
更新日期:2003-01-01 00:00:00
abstract::1. Na+/H+ exchange, an ethylisopropylamiloride (EIPA)-sensitive Na+ and HCO3- dependent system and a diisothio-cyanatostilbenedisulphonic acid (DIDS)-sensitive Na+ and HCO3- transporter, contribute to sodium influx and intracellular pH (pHi) regulation in vascular smooth muscle. 2. In cultured cells from the human int...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1991.tb01419.x
更新日期:1991-02-01 00:00:00
abstract::Microglia are the resident immune cells within the brain and retina, commonly known as the macrophages of the central nervous system (CNS). Microglia survey the surrounding milieu to eliminate invading microbes, clear cellular debris and enforce programmed cell death by removing apoptotic cells. Complementary to their...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12099
更新日期:2013-08-01 00:00:00
abstract::1. The leucocyte-mediated inflammatory response plays a pivotal role in ischaemia-reperfusion injury. P-Selectin and CD11b are important mediators for the recruitment of leucocytes into the endothelium. However, the time-course of changes in P-selectin and CD11b expression during reperfusion is not defined. Magnesium ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04697.x
更新日期:2007-12-01 00:00:00
abstract::1. In cats anaesthetized with alpha-chloralose, electrical stimulation (ES) of the trigeminal ganglion produced a fall in blood pressure, a predominantly ipsilateral dilatation in the common carotid vascular bed and bilateral dilatation of the middle meningeal vascular bed. Section of the trigeminal root abolished the...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb01206.x
更新日期:1997-06-01 00:00:00
abstract::1. In an isolated right atrial preparation, an increase in right atrial pressure (RAP) produces an increase in atrial rate. This rate response is larger and occurs faster when there is background vagal or muscarinic stimulation. 2. We hypothesized that in the latter situation, an increase in RAP antagonizes the effect...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05408.x
更新日期:2010-09-01 00:00:00
abstract::1. Intermittent bursts of activity are a robust feature of the discharges of sympathetic nerves. There are at least two major mechanisms producing such discharges: (i) phasic inputs influencing sympathetic circuits; and (ii) oscillators embedded within sympathetic networks. The functional significance of patterned and...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2001.03414.x
更新日期:2001-01-01 00:00:00
abstract::1. Angiotensin (Ang) II causes growth-related effects on vascular smooth muscle cells in vitro and in vivo. 2. Chronic infusions of AngII systemically, at doses that are initially subpressor, result in slowly progressive increases in arterial pressure ('slow-pressor' hypertension). It has been suggested that the hyper...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03590.x
更新日期:2001-12-01 00:00:00
abstract::A high-salt diet in rats has been shown to result in enhanced vasoconstrictor and/or reduced vasodilator responses of isolated arteries to agonists. The present experiments were designed to investigate the effects of dietary salt on the responses of the pressurized mesenteric resistance artery of the dog to constricto...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04069.x
更新日期:2004-10-01 00:00:00
abstract::1. Heparan sulfate proteoglycan in the basal lamina of smooth muscle cells is important in the maintenance of the 'contractile', high volume fraction of myofilaments (Vvmyo) phenotype. The mechanism by which this occurs may involve the continuous internalization of heparan sulfate by the smooth muscle cells themselves...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1991.tb01411.x
更新日期:1991-02-01 00:00:00
abstract::The beta-receptor stimulant effects of Sm220Cl, dl-N-(1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2-(3,4-dihydroxy-2-methoxyphenyl)ethylamine, and (-)-isoprenaline have been compared in isolated atrial (beta1) and tracheal (beta2) preparations from guinea-pigs and cats. 2. The compounds were also tested for their ability t...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1977.tb02672.x
更新日期:1977-07-01 00:00:00
abstract::1. Ionic channels appear to play an important role in contractile responses of the cerebral arteries and, thereby, contribute to the regulation of cerebral circulation. In the present study, we investigated the role of large-conductance Ca(2+)-activated K+ (BK(Ca)) channels in the regulation of cerebral arterial tone ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03688.x
更新日期:2002-07-01 00:00:00
abstract::1. The present report documents evidence suggesting that endothelin (ET) is a mediator and modulator of post-ganglionic sympathetic neuronal development. 2. Endothelin is produced by post-ganglionic neurons and by cells adjacent to these neurons. 3. Post-ganglionic sympathetic neurons express functional receptors for ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.1999.03179.x
更新日期:1999-12-01 00:00:00