Abstract:
:The present study examined the ability of the selective imidazoline I(2)-site ligands 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) and 2-[4,5-dihydroimidaz-2-yl]-quinoline (BU224) and selected monoamine oxidase (MAO) inhibitors to evoke locomotor activity in rats bearing a lesion of the nigrostriatal pathway. Male Sprague-Dawley rats were injected with 12.5 microg 6-hydroxydopamine (6-OHDA) into the right median forebrain bundle to induce a unilateral lesion of the nigrostriatal tract. After 6 weeks, test drugs were administered either alone or in combination with L-DOPA (l-3,4-dihydroxyphenylamine) and the circling behaviour of animals was monitored as an index of anti-Parkinsonian activity. Intraperitoneal (i.p.) administration of the irreversible MAO-B inhibitor deprenyl (20 mg kg(-1)) or the imidazoline I(2)-site ligands BU224 (14 mg kg(-1)) and 2-BFI (7 and 14 mg kg(-1)) produced significant increases in ipsiversive rotations compared to vehicle controls totaling, at the highest respective doses tested, 521 +/-120, 131 +/- 37 and 92.5 +/- 16.3 net contraversive rotations in 30 (deprenyl) or 60 (BU224 and 2-BFI) min. In contrast, the reversible MAO-A inhibitor moclobemide (2.5-10 mg kg(-1)) and the reversible MAO-B inhibitor lazabemide (2.5-10 mg kg(-1)) failed to instigate significant rotational behaviour compared to vehicle. Coadministration of lazabemide (10 mg kg(-1)), moclobemide (10 mg kg(-1)) or 2-BFI (14 mg kg(-1)) with L-DOPA (20 mg kg(-1)) significantly increased either the duration or total number of contraversive rotations emitted over the testing period in comparison to L-DOPA alone. These data suggest that I(2)-specific ligands have dual effects in the 6-OHDA-lesioned rat model of Parkinson's disease; a first effect associated with an increase in activity in the intact hemisphere, probably via an increase in striatal dopamine content, and a secondary action which, through the previously documented inhibition of MAO-A and/or MAO-B, increases the availability of dopamine produced by L-DOPA.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Macinnes N,Duty Sdoi
10.1038/sj.bjp.0706019subject
Has Abstractpub_date
2004-12-01 00:00:00pages
952-9issue
8eissn
0007-1188issn
1476-5381pii
sj.bjp.0706019journal_volume
143pub_type
杂志文章abstract::The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2 alpha to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea-pig. Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb11095.x
更新日期:1985-08-01 00:00:00
abstract::1. We aimed to determine whether there are any changes in responsiveness of the mesenteric arterial beds to phenylephrine (Phe) and KCl in exercise-trained rats, and whether vascular endothelium and/or vascular smooth muscle play a role in these changes. 2. Adult male rats were subjected to a swimming schedule every d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702697
更新日期:1999-08-01 00:00:00
abstract::Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703981
更新日期:2001-04-01 00:00:00
abstract::Cysteine is one of the two key sulfur-containing amino acids with important functions in redox homeostasis, protein functionality and metabolism. Cysteine is taken up by mammals via their diet and can also be derived from methionine via the transsulfuration pathway. The cellular concentration of cysteine is kept withi...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14464
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Nitric oxide (NO) is known to activate NO-sensitive guanylyl cyclase (NO-GC) and to elicit cGMP production. However, NO has also been proposed to induce cGMP-independent effects. It is accepted practice to use specific NO-GC inhibitors, such as ODQ or NS2028, to assess cGMP-dependent NO effects. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12275
更新日期:2013-09-01 00:00:00
abstract::In dog trachea in situ, perfused arterially with blood, isoprenaline, glyceryl trinitrate and N-nitroso-N-morpholinoamino-acetonitrile (SIN-1A) given intra-arterially, decreased tracheal tone which had been elevated by neostigmine and increased tracheal blood flow. Glyceryl trinitrate and SIN-1A were more effective on...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb16764.x
更新日期:1981-05-01 00:00:00
abstract::1. Mild stress plus mild pain (solvent injection) applied daily to neonatal mice induces hormonal, behavioural and metabolic changes perduring in the adult life. 2. We investigated whether daily mild stress to neonatal mice induces also long-term defined changes of immune response, and whether immune changes are preve...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704577
更新日期:2002-03-01 00:00:00
abstract::1. The variation with clock-hour in the behaviour of naive rats in a Y-maze has been recorded.2. The number of entries recorded was highest during the light period while the number of faecal boluses was highest during the dark period. Rearing showed a biphasic periodicity.3. The responses to LSD, mescaline and ampheta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08274.x
更新日期:1973-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The locus coeruleus (LC) is a major source of noradrenergic projections to the dorsal spinal cord, and thereby plays an important role in the modulation of nociceptive information. The LC receives inputs from substance P (SP)-containing fibres from other regions, and expresses the NK(1) tachykin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01820.x
更新日期:2012-06-01 00:00:00
abstract::1 The effects of pretreatment with aspirin, and of prostacyclin (PGI(2)) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.2 Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb09359.x
更新日期:1983-01-01 00:00:00
abstract::1. The release of 5-hydroxytryptamine (5-HT) from the cerebral cortex and caudate nucleus of brainstem-transected cats and from the cerebral cortex of rats anaesthetized with urethane was determined by radioenzymatic and biological assay. 2. The stimulation of nucleus linearis intermedius of raphe doubles the basal 5-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07863.x
更新日期:1979-04-01 00:00:00
abstract::1. The mechanisms underlying the vasodilator response to urocortin are incompletely understood. The present study was designed to examine the role of endothelial nitric oxide and Ba(2+)-sensitive K(+) channels in the endothelium-dependent component of urocortin-induced relaxation in the rat left anterior descending co...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704587
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Extrahepatic vasodilation and increased intrahepatic vascular resistance represent attractive targets for the medical treatment of portal hypertension in liver cirrhosis. In both dysfunctions, dysregulation of the contraction-mediating Rho kinase plays an important role as it contributes to alter...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00158.x
更新日期:2009-05-01 00:00:00
abstract::1. Recombinant human ETA receptors were expressed in a mouse fibroblast cell line (Ltk- cell) and functional coupling of the receptors with Ca2+ permeable channels at low concentrations of endothelin-1 (ET-1) was investigated using whole-cell recordings and monitoring the changes in intracellular free Ca2+ concentrati...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16358.x
更新日期:1995-06-01 00:00:00
abstract::1. The action of angiotensin on the circular and longitudinal muscle of the human colon has been studied in vitro. The ED50 value (g/ml) of circular muscle was 8.7 x 10(-8) and of longitudinal muscle 3.1 x 10(-8), while the corresponding figures for acetylcholine were 1.6 x 10(-6) and 1.1 x 10(-6), respectively. Angio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09553.x
更新日期:1970-05-01 00:00:00
abstract::1. An 'atypical' 5-HT2 receptor which is located on the endothelium of rat jugular vein has been described. In the present study we have further defined the nature of the 5-HT2 receptor subtype present in this preparation. 2. In experiments conducted in the presence of ketanserin to preclude involvement of 5-HT2 recep...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13240.x
更新日期:1995-01-01 00:00:00
abstract::1 A rat isolated gastric mucosal preparation was used to monitor histamine output and acid secretion during stimulation by different secretagogues. 2 In non-stimulated preparations, spontaneous histamine output decreased over 450 min. 3 Stimulation of secretion with 4 (5)-methylhistamine or dibutyryl cyclic adenosine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09190.x
更新日期:1982-05-01 00:00:00
abstract::1 Anthopleurin-B (AP-B, greater than 3 x 10(-9) M), a newly isolated polypeptide from sea anemone (Anthopleura xanthogrammica), caused powerful rhythmic contractions in the guinea-pig isolated vas deferens. The other polypeptides anthopleurin-A from A. xanthogrammica and anthopleurin-C from A. elegantissima, elicited ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb09951.x
更新日期:1981-09-01 00:00:00
abstract::1. The intravenous, subcutaneous and oral toxicity of ambenoxan in mice is reported.2. Ambenoxan is a centrally acting skeletal muscle relaxant shown to be effective in mice, rats, rabbits, dogs and monkeys without loss of the righting reflex.3. It had no peripheral neuromuscular blocking properties.4. Decerebrate rig...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb08515.x
更新日期:1970-02-01 00:00:00
abstract::1. The interactions between two K+ channel openers, cromakalim and SR 44866 (infused i.v. at equihypotensive doses), and the sympathetic nervous system at the systemic and regional (mesentery, kidney, hindlimb) vascular levels were investigated in the pithed spontaneously hypertensive rat (SHR) by use of the pulsed Do...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb15846.x
更新日期:1990-07-01 00:00:00
abstract::1. The effects of some drugs known to inhibit transmission in the superior cervical ganglion and at the neuromuscular junction were investigated on the cholinergic nerve-smooth muscle junction, using the rat isolated innervated urinary bladder preparation.2. HC-3 and Win 4981 inhibited the indirectly evoked contractio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09900.x
更新日期:1970-08-01 00:00:00
abstract::1. The ability of the neuroprotective agent, lifarizine (RS-87476), to mitigate veratridine-, cyanide- and glutamate-induced toxicity in rat embryonic cerebrocortical neurones in primary culture has been compared with that of tetrodotoxin (TTX), nitrendipine, (+)-MK-801 and (-)-MK-801. Lactate dehydrogenase (LDH) rele...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13357.x
更新日期:1995-04-01 00:00:00
abstract::1. Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the pharmacological profile of the receptor mediating the acid secretory response to PYY. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701767
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Recent studies suggest that the effects of cyclooxygenase-2 (COX-2) inhibition are mediated by cannabinoid receptor activation. However, some non-steroidal anti-inflammatory drugs inhibit the enzyme fatty acid amide hydrolase, which regulates levels of some endocannabinoids. Whether COX-2 directl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00703.x
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:GoSlo-SR compounds are efficacious BK (KCa 1.1) channel openers, but little is known about their mechanism of action or effect on bladder contractility. We examined the effects of two closely related compounds on BK currents and bladder contractions. EXPERIMENTAL APPROACH:A combination of electr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13085
更新日期:2015-05-01 00:00:00
abstract::Oestrogens are important sex hormones central to health and disease in both genders that have protective effects on the cardiovascular and metabolic systems. These hormones act in complex ways via both genomic and non-genomic mechanisms. The genomic mechanisms are relatively well characterized, whereas the non-genomic...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01235.x
更新日期:2011-07-01 00:00:00
abstract::1 Eleven analogues of sodium cromoglycate have been tested for their ability to suppress histamine release induced by anti-IgE from passively sensitized human lung fragments in vitro. 2 With the exception of WY 16922, which released histamine at high concentrations, all inhibited histamine release in a linear dose-rel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb07937.x
更新日期:1980-10-01 00:00:00
abstract::1. Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function is associated with reduced endoneural blood flow (EBF) which may contribute to nerve dys...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702856
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Voltage-operated sodium channels constitute major target sites for local anaesthetic-like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.255
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Volume-regulated anion channels (VRACs) play an important role in cell-volume regulation. alpha(1)-Adrenoceptor stimulation by phenylephrine (PE) suppressed the hypotonic activation of VRAC current in mouse ventricular cells and regulatory volume decrease (RVD) was also absent in PE-treated cells...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00896.x
更新日期:2010-09-01 00:00:00