Abstract:
:1. To determine the role of G protein-coupled receptor kinases (GRKs) in the regulation of endogenous secretin receptor responsiveness, we have transiently overexpressed both wild-type (WT) and dominant negative mutant (DNM) GRKs in NG108-15 mouse neuroblastoma x rat glioma hybrid cells and investigated the effects of this on agonist-stimulated adenylyl cyclase activity. 2. Overexpression of WT GRK6 selectively inhibited secretin-stimulated cyclic AMP accumulation (fold stimulation of cyclic AMP above basal following 15 min incubation with 100 nM secretin was 12.1+/-2.0 and 6.2+/- 0.8 in control and WT GRK overexpressing cells, respectively) without affecting cyclic AMP responses mediated by the adenosine A(2) receptor agonist 5'-(N-ethylcarboxamido) adenosine (NECA) or the prostanoid-IP receptor agonist iloprost, or the direct activator of adenylyl cyclase, forskolin. On the other hand DNM GRK6 (Lys(215)Arg) overexpression produced the opposite effect--a selective increase in the secretin-stimulated cyclic AMP response was observed in cells overexpressing DNM GRK6 compared to plasmid-transfected cells (fold stimulation of cyclic AMP above basal following 15 min incubation with 100 nM secretin was 12.6+/-2.7 and 29.6+/-5.6 for control and DNM GRK6-overexpressing cells, respectively). 3. Overexpression of WT GRK5 likewise inhibited the secretin-stimulated cyclic AMP response, however, this effect was not as selective as with GRK6, since adenosine A(2) receptor responsiveness was also suppressed by GRK5 overexpression. Unlike DNM GRK6, overexpression of DNM GRK5 failed to modulate secretin or A(2) adenosine receptor signalling suggesting that endogenous GRK5 is unlikely to regulate desensitization of these receptors in NG108-15 cells. 4. Overexpression of WT GRK2 did not affect secretin-stimulated cyclic AMP accumulation. Instead, GRK2 overexpression selectively inhibited A(2) adenosine receptor responsiveness, confirming our previous findings. 5. Together these results suggest a selective role of endogenous GRK6 in regulating secretin receptor responsiveness in NG108-15 cells. In addition, these data indicate that GRKs exert a surprising degree of selectivity in the regulation of natively expressed GPCR responses.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ghadessy RS,Willets JM,Kelly Edoi
10.1038/sj.bjp.0705101subject
Has Abstractpub_date
2003-02-01 00:00:00pages
660-70issue
4eissn
0007-1188issn
1476-5381journal_volume
138pub_type
杂志文章abstract::1. The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in a canine model of coronary cyclic flow having some of the characteristics of acute unstable angina. Heparin was studied as a reference anticoagulant. 2. Localized endothelial damage was induced in the circumflex coronary artery ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15460.x
更新日期:1996-06-01 00:00:00
abstract::The peptides, neurotensin, substance P, somatostatin, and bombesin, several analogues and fragments of neurotensin and compound 48/80, all caused the secretion of both endogenous 5-hydroxytryptamine (5-HT) and histamine. There was no differential effect of any of the secretagogues tested on the secretion of 5-HT and h...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10069.x
更新日期:1984-02-01 00:00:00
abstract::1. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused alb...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1991.tb09844.x
更新日期:1991-07-01 00:00:00
abstract::1. In Ca-free solution, the contractile response of guinea-pig taenia caecum to 10(-4) M carbachol was mediated through muscarinic receptors and was reduced time-dependently by desensitization with 10(-4) M carbachol, but not 10(-4) M histamine. On the other hand, the response to 10(-4) M histamine was shown to be med...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11600.x
更新日期:1988-07-01 00:00:00
abstract::1. Fluoxetine (Prozac) is widely used as an antidepressant drug and is assumed to be a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI). Claims that its beneficial psychotropic effects extend beyond those in treatment of depression have drawn clinical and popular attention to this compound, raising the q...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701545
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Mast cells are important in allergic reactions. Here, we assessed the anti-allergic effects of the anti-cancer drug tozasertib specifically regarding regulatory effects on mast cell activation. EXPERIMENTAL APPROACH:Tozasertib effects on mast cell degranulation were determined by measuring β-hex...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15012
更新日期:2020-06-01 00:00:00
abstract::1 The effects of prostaglandin (PGE(1)), following local administration during different phases of developing sponge-induced granulomata, were studied in normal and essential fatty acid deficient (EFAD) rats.2 In normal rats, a single dose of 1 mug PGE(1) on implantation (day 1) increased exudate production without al...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07852.x
更新日期:1979-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Imiquimod is an immunomodulator approved for the treatment of basal cell carcinoma and has adverse side effects, including taste disturbances. Paracrine transmission, representing cell-cell communication within taste buds, has the potential to shape the final signals that taste buds transmit to t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13567
更新日期:2016-11-01 00:00:00
abstract::In recent years there has been a growing recognition of the influence of sex on brain structure and function, and in relation, on the susceptibility, prevalence and response to treatment of psychiatric disorders. Most theories and descriptions of the effects of sex on the brain are dominated by an analogy to the curre...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12732
更新日期:2014-10-01 00:00:00
abstract::1. Caffeine has been widely used as a pharmacological tool to evaluate Ca(2+) release from the sarcoplasmic reticulum in isolated smooth muscle cells. However, in nervous tissue this drug also causes neurotransmitters release, which might cause additional effects when smooth muscle strips are evaluated. To assess this...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0705348
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Chromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle asse...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13782
更新日期:2017-06-01 00:00:00
abstract::The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb08990.x
更新日期:1987-05-01 00:00:00
abstract::1. In circular smooth muscle of the guinea-pig gastric fundus, transmural nerve stimulation evoked a cholinergic excitatory junction potential (e.j.p.), and blockade of the e.j.p. by atropine revealed a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (i.j.p.). 2. The amplitude of the e.j.p. was inc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15290.x
更新日期:1996-03-01 00:00:00
abstract::1. To characterize the muscarinic receptors on human pulmonary veins associated with the acetylcholine (ACh)-induced relaxation, isolated venous and arterial preparations were pre-contracted with noradrenaline (10 microM) and were subsequently challenged with ACh in the absence or presence of selective muscarinic anta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703301
更新日期:2000-05-01 00:00:00
abstract::Following identification of the human motilin receptor, we isolated the rabbit orthologue by PCR amplification and found this to be 85% identical to the open reading frame of the human receptor. The protein encoded was 84% identical to the human polypeptide. In HEK293T cells transfected with the rabbit receptor, motil...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0705505
更新日期:2003-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The endocannabinoid system and the cannabinoid CB(1) receptor have been identified in human sperm, and it is well known that endocannabinoids have pronounced adverse effects on male and female reproduction. In order to elucidate further the pathophysiological role of the endocannabinoid system in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00570.x
更新日期:2010-02-01 00:00:00
abstract::Ginsenoside Rg1, an active ingredient in ginseng, was previously shown to be a novel class of potent phytoestrogen. The present study aims at investigating the molecular mechanisms involved in mediating its actions in human breast cancer (MCF-7) cells. Rg1 (1 pM) stimulates cell proliferation (P<0.01) and estrogen-res...
journal_title:British journal of pharmacology
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更新日期:2006-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigated, in a mouse model, the effect of exercise intensity during chronic nicotine exposure on nicotine withdrawal severity, binding of α4β2*, α7 n...
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abstract::1. The effect of intradermally injected endotoxin on skin blood flow was investigated in anaesthetized male Wistar rats in vivo. 2. Local skin blood flow changes were measured hourly for 6 h in the shaved dorsal skin with a laser-Doppler flow probe and compared to changes in control sites which had been injected with ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14441.x
更新日期:1992-08-01 00:00:00
abstract::1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases t...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1975.tb07414.x
更新日期:1975-05-01 00:00:00
abstract::We investigated whether 10 days' in vivo treatment with nitroglycerine (NTG) would inhibit nitric oxide production by the endothelial cells of resistance arteries ex vivo and, if so, what the underlying mechanism might be. ACh increased the intracellular nitric oxide concentration ([NO]i; estimated using the nitric ox...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0706365
更新日期:2005-10-01 00:00:00
abstract::Perivascular adipose tissue (PVAT) is now recognized as an active player in vascular homeostasis. The expansion of PVAT in obesity and its possible role in vascular dysfunction have attracted much interest. In terms of the regulation of vascular tone and blood pressure, PVAT has been shown to release vasoactive mediat...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13767
更新日期:2017-10-01 00:00:00
abstract::Along with many other mammalian ATP-binding cassette (ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding proteins ranging from 638 to 678 amino acids in length. All f...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2011-12-01 00:00:00
abstract::In addition to their classical known effects, such as analgesia, impairment of cognition and learning and appetite enhancement, cannabinoids have also been related to the regulation of cardiovascular responses and implicated in cardiovascular pathology. Elevated levels of endocannabinoids have been related to the extr...
journal_title:British journal of pharmacology
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更新日期:2007-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The endocannabinoid, anandamide, has anti-arrhythmic effects. The aim of the present study was to explore the electrophysiological effects of anandamide on rat myocardium. EXPERIMENTAL APPROACH:Evoked action potentials (APs) were recorded using intracellular recording technique in rat cardiac pa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2009-12-01 00:00:00
abstract::1 The present study examined effects of agonist enzymes and receptor-activating peptides for protease-activated receptors (PARs) on duodenal motility in the rat, and also investigated possible mechanisms underlying the evoked responses. 2 Thrombin at 0.03-0.1 microM and the PAR-1-activating peptide SFLLR-NH2 at 3-100 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1999-10-01 00:00:00
abstract::1 Atrial pacing at progressively increasing frequencies was performed on unanaesthetized dogs through electrodes placed aseptically in the wall of the right atrium and exteriorized in the neck region. 2 Heart rate and two atrioventricular conduction (AVC) parameters, namely the Wenckebach Point (one or two systole blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09300.x
更新日期:1982-10-01 00:00:00
abstract::The endothelial 5-HT receptor mediating relaxation of pig pulmonary artery has been characterized using the selective 5-HT(2B) receptor agonist BW 723C86 and a variety of structurally diverse 5-HT receptor antagonists. If arterial rings with intact endothelium were precontracted with prostaglandin F(2alpha) (3 microM)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703341
更新日期:2000-06-01 00:00:00
abstract::1. Neural crest material from neurula stage Xenopus embryos was tissue cultured as small aggregates of cells or a single cell suspension. Isolated pigment cells differentiated after 2 days in culture. 2. Melatonin (10(-15) to 10(-13) M) induced pigment granule condensation; it was 10,000 times more effective than any ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07554.x
更新日期:1977-12-01 00:00:00