Abstract:
:1. Histamine stimulated the accumulation of total [3H]-inositol phosphates (IPn) in control HeLa cells with an EC50 of 3.7 +/- 0.7 microM in the presence of 10 mM LiCl. The maximum response to histamine after 15 min incubation was 43 +/- 5% over basal accumulation and occurred at a concentration of 1 mM histamine. 2. The histamine-induced IPn production in HeLa cells was confirmed as H1 receptor-mediated, since the H1 antagonist mepyramine (10(-6) M) inhibited the histamine response (10(-4) M) by 83 +/- 7%, whereas the H2 antagonist, ranitidine (10(-4) M), and H3 antagonist, thioperamide (10(-6) M), were ineffective. 3. Histamine (10(-4) M) pretreatment of HeLa cells for 30 min desensitized the subsequent histamine-induced IPn accumulation. The desensitized cells accumulated IPn in response to histamine with an EC50 of 1.7 +/- 0.7 microM after 15 min incubation. The maximum histamine-induced IPn accumulation at 10(-4) M was 19 +/- 5% over basal and was significantly lower (P < 0.03) than the maximum response in control cells. 4. The desensitization of histamine-induced IPn accumulation was time-dependent and, at a desensitizing histamine concentration of 10(-4) M, the half-maximal attenuation occurred after approximately 9 min and maximum desensitization was achieved by 15-20 min. The desensitization of the IPn accumulation was a reversible phenomenon and full recovery of the response occurred 150 min after the removal of the desensitizing histamine-containing medium. The half-time for the recovery of the histamine-induced response was estimated at 120 min. 5. Bradykinin stimulated IPn, accumulation in HeLa cells, and the ECm in control cells of 1.9 +/- 0.2 nM was not significantly different from the EC50 value from histamine-pretreated cells of 1.6 +/- 0.9 nM. The bradykinin response at 1 microM was 194 +/- 48% over basal IPn accumulation in control cells and this value was significantly different (P <0.04) from the 1 microM bradykinin-induced IPn accumulation in histamine pretreated HeLa cells of 143 +/- 38% over basal.6. NaF stimulated IP,, accumulation in control HeLa cells in a dose-related manner, with the maximum effect occurring at 15-20 mM. The EC50 value for NaF-stimulated IPn accumulation in control cells was 10.5 +/- 1.1 mm and the maximum response was 136 +/- 41% over basal after 20 min incubation. In histamine desensitized HeLa cells the EC50 value for NaF was 12.3 +/- 0.4 mM after 20 min stimulation,which was not significantly different from the value obtained in control cells. The maximum NaF stimulated IPn formation in desensitized cells of 68 +/- 23% over basal occurred at 15 -20 mM and was significantly lower (P<0.01) than that obtained in control cells.7. We show here that the acute histamine pretreatment of HeLa cells results in the desensitization of histamine H1 receptor-mediated IPn production. The desensitization was not restricted to the H1 receptor-mediated signal transduction pathway, but also includes both the bradykinin- and NaF mediated responses, supporting a heterologous desensitization mechanism. Our results are consistent with the site of attenuation being at or distal to the G-protein and the underlying mechanism being a slowed time-course for the production of inositol phosphates.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Bristow DR,Zamani MRdoi
10.1111/j.1476-5381.1993.tb13577.xsubject
Has Abstractpub_date
1993-06-01 00:00:00pages
353-9issue
2eissn
0007-1188issn
1476-5381journal_volume
109pub_type
杂志文章abstract::1. Yawning was induced by subcutaneous (s.c.) injection of low doses of apomorphine to rats. This effect decreased with increasing doses of the drug. 2. Intraperitoneal (i.p.) pretreatment of animals with sulpiride (D2-receptor blocker) reduced the frequency of the yawns induced by apomorphine, while SCH 23390 (D1-rec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11893.x
更新日期:1989-04-01 00:00:00
abstract::Effects of isoprenaline (Isop) on the contractile properties of the smooth muscle cells of cat trachea were investigated using intact and chemically skinned muscle preparations and an isometric tension recording method. In the intact muscle preparations, Isop 3 X 10(-10) or 3 X 10(-9) M significantly suppressed the am...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16221.x
更新日期:1984-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:There is increasing evidence that potassium channels are involved in the cardiovascular dysfunction of sepsis. This evidence was obtained after the systemic inflammation, cardiovascular dysfunction and organ damage had developed. Here we have studied the consequences of early interference with po...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01324.x
更新日期:2011-07-01 00:00:00
abstract::1. The relaxant effects of Zeneca ZD7114, BRL37344 (putative beta 3-adrenoceptor agonists) and various phenylethylamine-based agonists were studied in isolated ileum of the rat where tone was increased with carbachol (0.5 microM). Agonist-induced relaxation.was measured under equilibrium conditions with alpha-, beta 1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13972.x
更新日期:1993-12-01 00:00:00
abstract::1. Effects of KC399, an opener of ATP-sensitive K+ channels were investigated on membrane potential, isometric force and intracellular Ca2+ ([Ca2+]i) mobilization induced by acetylcholine (ACh) in smooth muscle from the rabbit trachea. 2. In these smooth muscle cells, ACh (0.1 and 1 microM) depolarized the membrane in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16642.x
更新日期:1995-08-01 00:00:00
abstract::Cyclo-oxygenase (COX) inhibitors potentiate opioid inhibition of GABAergic synaptic transmission in rat periaqueductal grey (PAG) (Vaughan et al., 1997). In the present study, the relative contribution of cyclo-oxygenase-1 (COX-1) and COX-2 inhibition to this phenomenon was examined by use of whole-cell patch clamp re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701818
更新日期:1998-04-01 00:00:00
abstract::1 Amodiaquine was found to be a potent inhibitor in vitro of gastric histamine methyltransferase from human and canine corpus and from pig antrum. The ID50 for the enzyme, purified from pig antrum mucosa by ultracentrifugation and chromatography on DEAE-cellulose, was 2.5 muM. 2 In six dogs with Heidenhanin pouches th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb06934.x
更新日期:1975-11-01 00:00:00
abstract::HMG-CoA reductase inhibitors (statins) have now become one of the most powerful pharmacological strategies in the treatment of cardiovascular diseases. Originally, the cardioprotective effects of statins were thought to be mediated through lipid lowering actions. However, it has now become increasingly clear that the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706863
更新日期:2006-10-01 00:00:00
abstract::1. The cardiovascular effects of bilateral injection into the hypothalamic paraventricular nuclei of selective mu-, delta-, and kappa-opioid receptor agonists were investigated in conscious, unrestrained Wistar Kyoto rats, chronically instrumented with pulsed Doppler flow probes for measurement of regional haemodynami...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb14976.x
更新日期:1995-06-01 00:00:00
abstract::1. Gastric acid secretory responses to pentagastrin were characterized in the rat isolated gastric mucosa. In particular, the mechanisms underlying fade, declining response upon continued stimulation, and tachyphylaxis, progressively reduced responses upon repeated stimulation, were investigated. 2. Pentagastrin, 10(-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11738.x
更新日期:1988-12-01 00:00:00
abstract::The POZ domain Krüppel-like zinc finger transcription repressor (POK family) contains many important molecules, including RP58, Bcl6 and PLZF. They function as transcription repressors via chromatin remodelling and histone deacetylation and are known to be involved in the development and tumourigenesis of various orga...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15265
更新日期:2020-09-22 00:00:00
abstract::1. Short-circuit current (SCC) technique was used to study the adrenoceptors involved in the electrogenic chloride secretion by cultured cauda epididymal epithelium of rats. Stimulation of the epithelium with noradrenaline (primarily beta 1-adrenoceptor selective agonist), salbutamol (beta 2-adrenoceptor selective ago...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14477.x
更新日期:1992-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing. EXPERIMENTAL APPROACH:In the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13503
更新日期:2016-07-01 00:00:00
abstract::1 The rectum isolated from the fowl was perfused with Tyrode solution via the caudal mesenteric artery. Noradrenaline and adrenaline were biologically or fluorimetrically assayed in perfusates collected before and during stimulation of Remak's nerve or of the periarterial nerves.2 Perfusates collected during nerve sti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07827.x
更新日期:1979-02-01 00:00:00
abstract::The physiological regulation of the immune system encompasses comprehensive anti-inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707264
更新日期:2007-08-01 00:00:00
abstract::1 The spasmogenic and spasmolytic effects of beta-lipotropin (LPH) fragments and one analogue were investigated on different parts of the gastro-intestinal tract of guinea-pig and rat in vitro.2 Changes in muscle tone were observed in colon and rectum and to a lesser extent in jejunum and ileum of both species. Rat co...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10849.x
更新日期:1980-04-01 00:00:00
abstract::1. Phenylephrine-induced contractions of rabbit isolated trigone and urethra were antagonized in a competitive manner by alfuzosin (pA2 7.44 and 7.30, respectively) and prazosin. 2. The characteristics of [3H]-prazosin binding to human prostatic adenoma tissue were evaluated. [3H]-prazosin was potently displaced by al...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13762.x
更新日期:1993-08-01 00:00:00
abstract::1. The effects of four specific inhibitors of 5-hydroxytryptamine (K-HT) uptake on morphine-, methadone- or pethidine-induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55 degrees C) reaction times. The effect of the compounds on the uptake of [3H]-5-HT into rat whole brai...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07881.x
更新日期:1979-04-01 00:00:00
abstract::1. We examined the effects of eprosartan, an AT(1) receptor antagonist, on the progression of left ventricular (LV) dysfunction and remodelling in dogs with heart failure (HF) produced by intracoronary microembolizations (LV ejection fraction, EF 30 to 40%). 2. Dogs were randomized to 3 months of oral therapy with low...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705032
更新日期:2003-01-01 00:00:00
abstract::1 The effects of microiontophoretically applied morphine and its interactions with the effects of microiontophoretic applications of either acetylcholine, (-)-noradrenaline or 5-hydroxytryptamine have been studied on single neurones in the brain stem of rats anaesthetized with urethane.2 Morphine excited or inhibited ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09591.x
更新日期:1974-01-01 00:00:00
abstract::1. In the present study we tested the hypothesis that insulin-like growth factor-1 (IGF-1) modulates resting chloride conductance (G(Cl)) of rat skeletal muscle by activating a phosphatase and that the chloride channel, based on the activity of phosphorylating-dephosphorylating pathways, has different sensitivity to s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702107
更新日期:1998-10-01 00:00:00
abstract::We utilized a rat model of myocardial infarction to investigate whether manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, and tumour necrosis factor- alpha (TNF-alpha) and/or interleukin-1beta (IL-1beta) are involved in the late phase of ischaemic preconditioning (IP). IP was induced in anaesthe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703594
更新日期:2000-10-01 00:00:00
abstract::1. The effects of seven agonist and three antagonist adenosine receptor ligands were compared on the guinea-pig sinoatrial (SA) node (isolated right atrium) and atrioventricular (AV) node (perfused whole heart). Single agonist concentration-effect curves were obtained to 5'-N-ethylcarboxamidoadenosine (NECA), R(-)-N6-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701891
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The development of subtype-selective ligands to inhibit voltage-sensitive sodium channels (VSSCs) has been attempted with the aim of developing therapeutic compounds. Tetrodotoxin (TTX) is a toxin from pufferfish that strongly inhibits VSSCs. Many TTX analogues have been identified from marine an...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13985
更新日期:2017-11-01 00:00:00
abstract::1 The effects of general anaesthetics on the responses of neurones to iontophoretically applied L-glutamate have been examined in slices of the guinea-pig olfactory cortex in vitro. 2 Concentrations of pentobarbitone, ether, methoxyflurance, trichloroethylene and alphaxalone that are known to depress synaptic transmis...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1976-11-01 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. We have examined the mechanisms by which the K(+)-channel blocker 4-aminopyridine (4-AP) can dose-dependently increase both basal [3H]-noradrenaline ([3H]-NA) release and the [3H]-NA release evoked by electrical stimulation, but not the release of [3H]-acetylcholine ([3H]-ACh), from slices of rat hippocampus. 2. Bo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12247.x
更新日期:1991-03-01 00:00:00
abstract::Psoriasis is a chronic inflammatory disease affecting 1-3% of the general population. Among psoriatic patients, 5-40% are affected by psoriatic arthritis. Due to the chronic nature of the disease, patients suffer from substantial psychological and financial burdens, thus adding to a significantly impaired quality of l...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.00702.x
更新日期:2010-06-01 00:00:00
abstract::1. Carrier mediated uptake (uptake-1) transport of norepinephrine (NE) plays a key role in the regulation of sympathetic neurotransmission. Recent investigations indicate that nitric oxide (NO) may modulate uptake-1 activity, possibly in a cyclic GMP independent manner. 2. Carrier mediated transport of [(3)H-NE] and [...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703416
更新日期:2000-07-01 00:00:00
abstract::1. Various neurotransmitters in the brain regulate gastric acid secretion. Previously, we reported that the central injection of kappa-opioid receptor agonists stimulated this secretion in rats. Although the existence of kappa(1)-kappa(3)-opioid receptor subtypes has been proposed, the character is not defined. We inv...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705082
更新日期:2003-03-01 00:00:00