Abstract:
BACKGROUND AND PURPOSE:Dilatation of cerebral and dural arteries causes a throbbing, migraine-like pain, indicating that these structures are involved in migraine. Clinical trials suggest that adenosine 5'-triphosphate-sensitive K(+) (K(ATP)) channel opening may cause migraine by dilatating intracranial arteries, including the middle meningeal artery (MMA). We studied the K(ATP) channel expression profile in rat MMA and examined the potential inhibitory effects of the K(ATP) channel blocker PNU-37883A on K(ATP) channel opener-induced relaxation of the rat MMA, using the three K(ATP) channel openers levcromakalim, pinacidil and P-1075. EXPERIMENTAL APPROACH:mRNA and protein expression of K(ATP) channel subunits in the rat MMA were studied by quantitative real-time PCR and western blotting, respectively. The in vivo and in vitro effects of the K(ATP) channel drugs on rat MMA were studied in the genuine closed cranial window model and in myograph baths, respectively. KEY RESULTS:Expression studies indicate that inwardly rectifying K(+) (Kir)6.1/sulphonylurea receptor (SUR)2B is the major K(ATP) channel complex in rat MMA. PNU-37883A (0.5 mg kg(-1)) significantly inhibited the in vivo dilatory effect of levcromakalim (0.025 mg kg(-1)), pinacidil (0.38 mg kg(-1)) and P-1075 (0.016 mg kg(-1)) in rat MMA. In vitro PNU-37883A significantly inhibited the dilatory responses of the three K(ATP) channel openers in rat MMA at 10(-7) and 3 x 10(-7) M. CONCLUSIONS AND IMPLICATIONS:We suggest that Kir6.1/SUR2B is the major functional K(ATP) channel complex in the rat MMA. Furthermore, we demonstrate the potent in vivo and in vitro blocking potentials of PNU-37883A on K(ATP) channel opener-induced relaxation of the rat MMA.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ploug KB,Boni LJ,Baun M,Hay-Schmidt A,Olesen J,Jansen-Olesen Idoi
10.1038/bjp.2008.86subject
Has Abstractpub_date
2008-05-01 00:00:00pages
72-81issue
1eissn
0007-1188issn
1476-5381pii
bjp200886journal_volume
154pub_type
杂志文章abstract::1 The action of iontophoretically administered lithium was studied on spinal Renshaw cells an interneurones and on supraspinal neurones in cerebral cortex, thalamus, hypothalamus and brain stem in anaesthetized cats and rats. 2 There was a correlation between the effects of Li+ and those of acetylcholine (ACh), althou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07740.x
更新日期:1977-06-01 00:00:00
abstract::1. The present experiments were designed to investigate the mechanisms causing intimal hyperplasia in connection with the impaired synergism between prostaglandin I2 (PGI2) and nitric oxide (NO) in human uterine arteries (UAs). 2. In order to assess the magnitude of intimal hyperplasia, the intima:media ratio (%) was ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15779.x
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Immunomodulatory tetracyclines are well-characterized drugs with a pharmacological potential beyond their antibiotic properties. Specifically, minocycline and doxycycline have shown beneficial effects in experimental colitis, although pro-inflammatory actions have also been described in macrophag...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14494
更新日期:2018-12-01 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::1. TRPM8 (CMR1) is a Ca(2+)-permeable channel, which can be activated by low temperatures, menthol, eucalyptol and icilin. It belongs to the transient receptor potential (TRP) family, and therefore is related to vanilloid receptor type-1 (VR1, TRPV1). We tested whether substances which are structurally related to ment...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705652
更新日期:2004-02-01 00:00:00
abstract::1. The effects of the nitrosothiol, S-nitroso N-acetylpenicillamine (SNAP) which liberates nitric oxide (NO), on ethanol-mediated gastric damage, blood flow and cyclic GMP levels in siaoloadenectomized (SALX) rats have been investigated. 2. Intraluminal instillation of ethanol (5-50% w/v) dose-dependently induced haem...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15883.x
更新日期:1995-05-01 00:00:00
abstract::The oestrogenic and antioestrogenic activities of a series of substituted derivatives of 1,1,2 triphenylbut-1-ene have been determined using primary cultures of rat pituitary gland cells to monitor prolactin synthesis in vitro. The relative binding affinity of the agonists for the oestrogen receptor was consistent wit...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10174.x
更新日期:1986-01-01 00:00:00
abstract::1. The binding of 2-[125I]-iodomelatonin to chicken brain membranes, and the inhibition of binding by melatonin, N-acetyltryptamine and luzindole, were examined at temperatures between 4 degrees C and 37 degrees C. 2. At all temperatures studied, the binding affinity (Kd or Ki) for 2-[125I]-iodomelatonin, melatonin (b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14059.x
更新日期:1994-01-01 00:00:00
abstract::The effects of N-(cyclopropylmethyl)-19-isopentylnororvinol hydrochloride (M320) on urine excretion by rats were investigated. Further studies, using rabbit isolated vas deferens, investigated its interactions with kappa-opiate receptors. The output of urine for a 2 h period after M320, administered subcutaneously to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11180.x
更新日期:1986-12-01 00:00:00
abstract::1. A method is presented which enables the dissociation constant (KI) of a competitive, pseudo-irreversible or non-competitive antagonist-receptor complex to be estimated without knowledge of agonist concentrations. 2. The technique has been tested using sets of concentration-response data which simulated these variou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14047.x
更新日期:1994-01-01 00:00:00
abstract::1. The effects of various metabotropic glutamate receptor agonists on [3H]-cyclic AMP accumulation and phosphoinositide hydrolysis were investigated in guinea-pig cerebral cortical slices prelabelled with [3H]-adenine or [3H]-inositol. 2. 1-Aminocyclopentane-1S,3R-dicarboxylate (1S,3R-ACPD), L-2-amino-4-phosphonobutan...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14069.x
更新日期:1994-01-01 00:00:00
abstract::1. The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea-pig trachea. 2. In the presence of indomethacin (3 microM) and propranolol (1 microM) two contractile phases were evident in both t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14174.x
更新日期:1990-12-01 00:00:00
abstract::1. The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responses2. After the p...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1476-5381.1968.tb07956.x
更新日期:1968-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Although picrotoxin is a well-established antagonist of GABA(A) receptors, detailed studies of its action on inhibitory synaptic transmission have not previously been made. EXPERIMENTAL APPROACH:Electrophysiological techniques were used to study the action of picrotoxin on inhibitory postsynapti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00542.x
更新日期:2010-02-01 00:00:00
abstract::1. Mouse islets were used to define the characteristics and study the mechanisms of the stimulation of insulin release by compound AZ-DF 265, 4-[[N-(alpha-phenyl-2-piperidino-benzyl) carbamoyl]methyl] benzoic acid, a substituted benzoic acid with an asymmetric carbon atom. 2. At a non-stimulatory concentration of gluc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11405.x
更新日期:1988-01-01 00:00:00
abstract::Antidromic stimulation of sensory peripheral branches of the trigeminal system (mental nerve) leads to cutaneous vasodilatation and increases vascular permeability in the rat. Antidromic vasodilatation is observed only at high intensity stimulation (10 V, 15 Hz, 0.2 or 5 ms) supporting the participation of afferent C-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb16144.x
更新日期:1985-03-01 00:00:00
abstract::Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMD...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0706086
更新日期:2005-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13240.x
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abstract::1. The signal transduction pathway for vasorelaxation induced by human alpha-calcitonin gene-related peptide (human alpha-CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10(-7) M). 2. Vasorelaxation by human alpha-CGRP was inhibited by haemoglobin (10(-6) M) and methylene blue (10(-5)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14508.x
更新日期:1992-11-01 00:00:00
abstract::1. The effect of basal tension (transmural tensions 235 +/- 29 mg wt (low tension: equivalent to approximately 16 mmHg) and 305 +/- 34 mg wt (high tension: equivalent to 35 mmHg)) on rat pulmonary resistance artery responses to endothelin-1 (ET-1) and the selective ET(B)-receptor agonist sarafotoxin S6c (S6c) were stu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1998-03-01 00:00:00
abstract::1. Phenylarsine oxide (PAO) is commonly used to inhibit tyrosine phosphatase activity. However, PAO can affect a variety of different processes because of its ability to promote sulfhydryl oxidation. In the present study, we investigated the effects that PAO has on basal and beta-adrenergically stimulated L-type Ca(2+...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705845
更新日期:2004-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16019.x
更新日期:1996-11-01 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::The modulatory effects of protein kinase C (PKC) on the activation of cytosolic phospholipase A2 (cPLA2) and adenylyl cyclase (AC) have recently been described. Since the signalling cascades associated with these events play critical roles in various functions of macrophages, we set out to investigate the crosstalk be...
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pub_type: 杂志文章
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更新日期:1998-12-01 00:00:00
abstract::1. The series of cycloalcohols C6, C7, C8 and C10 have been used to probe the molecular dimensions of a variety of general anaesthetic target sites. 2. The general anaesthetic EC50 concentrations of the cycloalcohols were determined for tadpoles (Xenopus laevis). All of the cycloalcohols tested were found to be potent...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12148.x
更新日期:1991-01-01 00:00:00
abstract::1. The electrophysiological effects of prazosin, a highly specific alpha 1-adrenoceptor antagonist, on transmembrane action potential characteristics were studied in guinea-pig papillary muscles. 2. At concentrations between 10(-6) M and 10(-5) M, prazosin produced a concentration-dependent decrease in the maximum ups...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14796.x
更新日期:1994-03-01 00:00:00
abstract::1. A synthetic oxytocin analogue, [1-N-carbamoyl-hemicystine-2-O-methyltyrosine]-oxytocin (carbamoyl-methyloxytocin), has been tested as an antagonist to the actions of oxytocin and vasopressin on the uterus, the mammary gland and blood pressure.2. The analogue inhibited the response of the isolated rat uterus to both...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09927.x
更新日期:1970-10-01 00:00:00
abstract::1. Voltage-operated calcium channel (VOCC) antagonists are effective antihypertensive and antianginal agents but they also depress myocardial contractility. 2. We compared four L-type calcium channel antagonists, felodipine, nifedipine, amlodipine and verapamil and a relatively T-type selective calcium channel antagon...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702045
更新日期:1998-09-01 00:00:00