bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of noradrenaline‐induced vasorelaxation in isolated femoral arteries of the neonatal rat
Authors: Nishina H , Ozaki T , Hanson M A , Poston L 
Published: January 2005

Isolated arteries from the femoral circulation of Wistar rats mounted on a small vessel myograph demonstrated age related tension development to noradrenaline (NA, 1×10−8–5×10−5 M) day 20 greater than day 10 (P < 0.005); day 100 greater than day 20 (P < 0.001) and depolarizing potassium (125 mM) buffer day 20 greater than day 10 (P < 0.001). NA evoked dilatation in femoral arteries from neonatal rats (10 days) when added to unstimulated vessels or to those preconstricted with the thromboxane mimetic, U46619. Relaxation to NA was inhibited by L‐NAME (0.1 mM) (P < 0.001), endothelial removal (P < 0.001) and the α2‐adrenoceptor antagonist, yohimbine (0.1 μM) (P < 0.001). α1‐ or β‐adrenoceptor antagonism was without effect. Relaxation was evoked in femoral arteries of the 10‐day‐old rats by the α2‐adrenoceptor agonist UK14304 (1×10−8–5×10−5 M). This relaxation was also abolished by L‐NAME (0.1 mM) (P < 0.001) or endothelial removal (P < 0.001). α2‐adrenoceptor‐mediated vasorelaxation was the predominant response to NA stimulation in femoral arteries of the neonatal rat. These responses were endothelium‐dependent and were NO‐mediated.British Journal of Pharmacology (1999) 127, 809–812; doi:10.1038/sj.bjp.0702641
Separation of M‐like current and ERG current in NG108‐15 cells
Authors: Meves Hans , Schwarz Jürgen R , Wulfsen Iris 
Published: January 2005

Differentiated NG108‐15 neuroblastoma×glioma hybrid cells were whole‐cell voltage‐clamped. Hyperpolarizing pulses, superimposed on a depolarized holding potential (−30 or −20 mV), elicited deactivation currents which consisted of two components, distinguishable by fitting with two exponential functions.
Linopirdine [DuP 996, 3,3‐bis(4‐pyridinylmethyl)‐1‐phenylindolin‐2‐one), a neurotransmitter‐release enhancer known as potent and selective blocker of the M‐current of rat sympathetic neurons, in concentrations of 5 or 10 μM selectively inhibited the fast component (IC50=14.7 μM). The slow component was less sensitive to linopirdine (IC50>20 μM).
The class III antiarrhythmics [(4‐methylsulphonyl)amido]benzenesulphonamide (WAY‐123.398) and 1‐[2‐(6‐methyl‐2‐pyrydinil)ethyl]‐4‐(4‐methylsulphonylaminobenzoyl) piperidine (E‐4031), selective inhibitors of the inwardly rectifying ERG (ether‐à‐go‐go‐related gene) potassium channel, inhibited predominantly the slow component (IC50=38 nM for E‐4031). The time constant of the WAY‐123.398‐sensitive current resembled the time constant of the slow component in size and voltage dependence.
Inwardly rectifying ERG currents, recorded in K+‐rich bath at strongly negative pulse potentials, resembled the slow component of the deactivation current in their low sensitivity to linopirdine (28% inhibition at 50 μM).
The size of the slow component varied greatly between cells. Accordingly, varied the effect of WAY‐123.398 on deactivation current and holding current.
RNA transcripts for the following members of the ether‐à‐go‐go gene (EAG) K+ channel family were found in differentiated NG108‐15 cells: ERG1, ERG2, EAG1, EAG‐like (ELK)1, ELK2; ERG3 was only present in non‐differentiated cells. In addition, RNA transcripts for KCNQ2 and KCNQ3 were found in differentiated and non‐differentiated cells.
We conclude that the fast component of the deactivation current is M‐like current and the slow component is deactivating ERG current. The molecular correlates are probably KCNQ2/KCNQ3 and ERG1/ERG2, respectively.

British Journal of Pharmacology (1999) 127, 1213–1223; doi:10.1038/sj.bjp.0702642
Rundown of somatodendritic N‐methyl‐D‐aspartate (NMDA) receptor channels in rat hippocampal neurones: evidence for a role of the small GTPase RhoA
Authors: Nörenberg Wolfgang , Hofmann Fred , Illes Peter , Aktories Klaus , Meyer Dieter K 
Published: January 2005

Actin filament (F‐actin) depolymerization leads to the use‐dependent rundown of N‐methyl‐D‐aspartate (NMDA) receptor activity in rat hippocampal neurones. Depolymerization is promoted by Ca2+ which enters the cells via NMDA receptor channels. The ras homologue (Rho) GTPases (RhoA, Rac1 and Cdc42) promote actin polymerization and thus control the actin cytoskeleton. We have investigated, by means of the whole‐cell patch clamp technique, whether the actin fibres which interact with NMDA receptors are controlled by Rho GTPases.
In the presence of intracellular ATP which attenuates rundown, the C3 toxin from Clostridium (C.) botulinum was used to inactivate RhoA. Indeed, it enhanced the use‐dependent rundown of NMDA‐evoked inward currents to a level similar to that obtained in the absence of ATP.
Lethal toxin from Clostridium sordellii which inactivates Rac1 and Cdc42 lacked this effect.
We suggest that the function of somatodendritic NMDA receptor channels in rat hippocampal neurones can be modulated by RhoA via its action on F‐actin.

British Journal of Pharmacology (1999) 127, 1060–1063; doi:10.1038/sj.bjp.0702643
Pharmacological characterization of endothelin receptor subtypes in the guinea‐pig prostate gland
Authors: Lau Winnie A K , Cox Sandra L , Pennefather Jocelyn N , Mitchelson Fred J 
Published: January 2005

Experiments have been conducted to investigate the actions of endothelins on the guinea‐pig prostate gland.
Saturation experiments with [125I]‐endothelin‐1 (2–800 pM) in guinea‐pig prostatic homogenates indicated the presence of high affinity binding sites with an equilibrium dissociation constant (KD) of 230±50 pM, a maximum number of binding sites (Bmax) of 52±16 fmol mg−1 protein or 269±61 fmol g−1 tissue and a Hill coefficient (nH) of 1.01±0.03 (n=3). Competition experiments revealed that binding of [125I]‐endothelin‐1 (20 pM) was inhibited with the following order of potency: endothelin‐1 >>BQ‐788 (N‐cis‐2,6‐dimethylpiperidinocarbonyl‐L‐γ‐methyl‐Leu‐D‐Trp[1‐CO2CH3‐D‐Nle‐ONa])>BQ‐123 (cyclo‐D‐Asp‐L‐Pro‐D‐Val‐Leu‐D‐Trp) sarafotoxin S6c.
At concentrations with negligible influence on smooth muscle tone, endothelin‐1, endothelin‐2 and sarafotoxin S6b (1 nM–0.1 μM) produced concentration‐dependent potentiation of the contractions evoked by electrical field stimulation with trains of 20 pulses at 10 Hz every 50 s, 0.5 ms pulse width and a dial setting of 60 V. In contrast, the endothelin ETB receptor‐preferring agonist endothelin‐3 (1 nM–1 μM) was much less potent, and the endothelin ETB receptor‐selective agonists sarafotoxin S6c and BQ‐3020 (Ac‐[Ala11,15]‐endothelin‐1 (6–21)), up to 1 μM, were without effect.
The endothelin ETA receptor antagonist BQ‐123 (1 μM) markedly inhibited the potentiation induced by endothelin‐1, endothelin‐2 and sarafotoxin S6b while the endothelin ETB receptor antagonist BQ‐788 (1 μM) was less effective.
While our binding data indicates the presence of ETA and ETB binding sites in the guinea‐pig prostate, the endothelin‐induced facilitation of neurotransmission to the prostatic smooth muscle is mediated largely via activation of endothelin receptors of the ETA subtype.

British Journal of Pharmacology (1999) 127, 1091–1098; doi:10.1038/sj.bjp.0702644
Functional characterization and m‐RNA expression of 5‐HT receptors mediating contraction in human umbilical artery
Authors: Lovren Fina , Li Xiao‐Fang , Lytton Jonathan , Triggle Chris 
Published: January 2005

5‐HT1‐like and 5‐HT2 receptors have both been described to mediate contractions to 5‐HT in the human umbilical artery (HUA). However, the nature of the 5‐HT receptor subtypes is unknown.
In isometric force studies with ring preparations of HUA α‐methyl‐5‐hydroxytryptamine (α‐Me‐5‐HT) and 5‐hydroxytryptamine (5‐HT) contracted HUA with pED50 values of 8.04 and 7.74, respectively. In the presence of a subthreshold concentration of another vasoconstrictor sumatriptan and 5‐nonyloxytryptamine elicited concentration‐dependent contractions with pEC50 values of 7.21 and 7.67, respectively.
In the presence of the selective 5‐HT1B/D receptor antagonist GR127935, contractile responses elicited by sumatriptan and 5‐nonyloxytryptamine were competitively antagonized (pKB 9.01 and 9.02, respectively). In the experiments with 5‐HT, GR127935 appeared to be non‐competitive with shallow Schild plot slopes. The data were fitted with two linear regression lines and the calculated pKB of the high affinity component (8.90) was comparable to that expected for GR127935 at the 5‐HT1B/1D receptor.
Several 5‐HT2 selective receptor antagonists (spiperone, cyproheptadine, pirenperone) competitively inhibited responses to 5‐HT. The selective 5‐HT2A antagonist ketanserin against sumatriptan and 5‐nonyloxytryptamine behaved as a weak antagonist while against 5‐HT demonstrated a competitive antagonism (pKB 8.56).
Using specific primers for human 5‐HT1B, 5‐HT1D and 5‐HT2A receptor genes, the reverse transcriptase‐polymerase chain reaction revealed mRNA expression of 5‐HT1B and 5‐HT2A receptors in the HUA.
The results suggest that the HUA has a functional population of 5‐HT1B and 5‐HT2A receptor subtypes which are involved in the contractile response to 5‐HT. Contractions mediated by 5‐HT1B receptors can be ‘uncovered’ by exposure to other vasoactive agents.

British Journal of Pharmacology (1999) 127, 1247–1255; doi:10.1038/sj.bjp.0702647
Regulation of epidermal homeostasis through P2Y2receptors
Authors: Dixon C Jane , Bowler Wayne B , Littlewood‐Evans Amanda , Dillon Jane P , Bilbe Graeme , Sharpe Graham R , Gallagher James A 
Published: January 2005

Previous studies have indicated a role for extracellular ATP in the regulation of epidermal homeostasis. Here we have investigated the expression of P2Y2receptors by human keratinocytes, the cells which comprise the epidermis.Reverse transcriptase‐polymerase chain reaction (RT–PCR) revealed expression of mRNA for the G‐protein‐coupled, P2Y2receptor in primary cultured human keratinocytes.In situhybridization studies of skin sections revealed that P2Y2receptor transcripts were expressed in the native tissue. These studies demonstrated a striking pattern of localization of P2Y2receptor transcripts to the basal layer of the epidermis, the site of cell proliferation.Increases in intracellular free Ca2+concentration ([Ca2+]i) in keratinocytes stimulated with ATP or UTP demonstrated the presence of functional P2Y receptors.In proliferation studies based on the incorporation of bromodeoxyuridine (BrdU), ATP, UTP and ATPγS were found to stimulate the proliferation of keratinocytes.Using a real‐time firefly luciferase and luciferin assay we have shown that under static conditions cultured human keratinocytes release ATP.These findings indicate that P2Y2receptors play a major role in epidermal homeostasis, and may provide novel targets for therapy of proliferative disorders of the epidermis, including psoriasis.British Journal of Pharmacology(1999)127, 1680–1686; doi:10.1038/sj.bjp.0702653
Induction of eotaxin expression and release from human airway smooth muscle cells by IL‐1β and TNFα: effects of IL‐10 and corticosteroids
Authors: Chung K Fan , Patel Hema J , Fadlon Emma J , Rousell Jonathan , Haddad El‐Bdaoui , Jose Peter J , Mitchell Jane , Belvisi Maria 
Published: January 2005

Eotaxin is a novel C‐C chemokine with selective chemoattractant activity for eosinophils. We determined whether eotaxin could be produced by human airway smooth muscle (HASM) cells in culture and examined its regulation by interleukin‐10 (IL‐10) and the corticosteroid, dexamethasone.
Stimulation of the cells with interleukin‐1β (IL‐1β) or tumour necrosis factor (TNFα) each at 10 ng ml−1 induced the release of eotaxin protein with maximal accumulation by 24 h. Interferon‐γ (IFNγ) alone at 10 ng ml−1 had no effect and there was no synergy between these cytokines on the release of eotaxin.
Reverse phase high performance liquid chromatographic (HPLC) analysis of supernatents from cells treated with TNFα (10 ng ml−1 for 96 h showed immunoreactivity to eotaxin which eluted with the expected retention time of 34.5–35 min.
Both IL‐1β and TNFα‐induced release of eotaxin was not inhibited by dexamethasone (1 μM), however IL‐10 (10 ng ml−1) had a significant inhibitory effect. Dexamethasone and IL‐10 did not inhibit the induction of eotaxin mRNA induced by IL‐1β or TNFα.
Thus, human airway smooth muscle cells can release eotaxin and could be an important source of chemokine production during airway inflammatory events.

British Journal of Pharmacology (1999) 127, 1145–1150; doi:10.1038/sj.bjp.0702660
Pharmacological characterization of Ca2+ entry channels in endothelin‐1‐induced contraction of rat aorta using LOE 908 and SK&F 96365
Authors: Zhang Xiao‐Feng , Iwamuro Yasushi , Enoki Taijiro , Okazawa Makoto , Lee Ken , Komuro Taro , Minowa Tetsuya , Okamoto Yasuo , Hasegawa Hiroshi , Furutani Hidekatsu , Miwa Soichi , Masaki Tomoh 
Published: January 2005

We have recently shown that endothelin‐1 (ET‐1) activates two types of Ca2+‐permeable nonselective cation channels (designated NSCC‐1 and NSCC‐2) and store‐operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. Here we characterized Ca2+ entry channels involved in ET‐1‐induced contractions of rat thoracic aortic rings and increases in the intracellular free Ca2+ concentration ([Ca2+]i) of single smooth muscle cells using these blockers.
LOE 908 or a blocker of voltage‐operated Ca2+ channel nifedipine had no effect on the contractions and increases in [Ca2+]i induced by thapsigargin or ionomycin, whereas SK&F 96365 abolished them.
The contractions and increases in [Ca2+]i induced by ET‐1 depended on extracellular Ca2+ but were resistant to nifedipine. The responses to lower concentrations (0.1 nM) of ET‐1 were abolished by either SK&F 96365 or LOE 908. The responses to higher concentrations (1 nM) were abolished by SK&F 96365, but were partially resistant to LOE 908.
SK&F 96365 inhibited the LOE 908‐resistant contractions induced by higher concentrations of ET‐1 with IC50 values similar to those for contractions induced by thapsigargin or ionomycin.
These results show that the contractions and increases in [Ca2+]i of rat aortic smooth muscles at lower concentrations of ET‐1 involve only one Ca2+ entry channel which is sensitive to SK&F 96365 and LOE 908 (NSCC‐2), whereas those at higher concentrations of ET‐1 involve another Ca2+ entry channel which is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC) in addition to the former channel.

British Journal of Pharmacology (1999) 127, 1388–1398; doi:10.1038/sj.bjp.0702661
Contribution of cytochrome P450 epoxygenase and hydroxylase pathways to afferent arteriolar autoregulatory responsiveness
Authors: Imig John D , Falck John R , Inscho Edward W 
Published: January 2005

Previous studies have demonstrated an important role for the cytochrome P450 (CYT‐P450) pathway in afferent arteriole autoregulatory responses but the involvement of specific pathways remains unknown. Experiments were performed to determine the role of CYT‐P450 epoxygenase and hydroxylase pathways in pressure mediated preglomerular autoregulatory responses.
Afferent arteriolar diameter was measured as renal perfusion pressure was increased from 80–160 mmHg. Afferent arteriolar diameter averaged 19±2 μm at a renal perfusion pressure of 80 mmHg and decreased by 15±2% when pressure was increased to 160 mmHg.
Inhibition of the epoxygenase pathway with 6‐(2‐proparglyloxyphenyl)hexanoic acid (PPOH), enhanced the microvascular response to increasing renal perfusion pressure. In the presence of 50 μM PPOH, afferent arteriolar diameter decreased by 29±4% when pressure was increased from 80–160 mmHg.
Likewise, the sulphonimide derivative of PPOH, N‐methylsulphonyl‐6‐(2‐proparglyloxyphenyl) hexanamide (MS‐PPOH, 50 μM), enhanced the afferent arteriolar response to increasing renal perfusion pressure.
In contrast, the selective CYT‐P450 hydroxylase inhibitor, N‐methylsulphonyl‐12,12‐dibromododec‐11‐enamide (DDMS) attenuated the vascular response to increasing renal perfusion pressure. In the pressure of 25 μM DDMS, afferent arteriolar diameter decreased by 4±2% when pressure was increased from 80–160 mmHg.
These results suggest that CYT‐P450 metabolites of the epoxygenase pathway alter afferent arteriolar responsiveness and thereby modify the ability of the preglomerular vasculature to autoregulate renal blood flow. Additionally, these results provide further support to the concept that a metabolite of the hydroxylase pathway is an integral component of the afferent arteriolar response to elevations in perfusion pressure.

British Journal of Pharmacology (1999) 127, 1399–1405; doi:10.1038/sj.bjp.0702662
Involvement of ATP‐sensitive potassium channels in a model of a delayed vascular hyporeactivity induced by lipopolysaccharide in rats
Authors: Sorrentino Raffaella , Di Villa Bianca Roberta d'Emmanuele , Lippolis Laura , Sorrentino Ludovico , Autore Giuseppina , Pinto Aldo 
Published: January 2005

We have investigated the role of ATP‐sensitive potassium (KATP) channels in an experimental model of a delayed phase of vascular hyporeactivity induced by lipopolysaccharide (LPS) in rats.
After 24 h, from LPS treatment, in anaesthetized rats the bolus injection of phenylephrine (PE) produced an increase in mean arterial pressure (MAP) significantly (P<0.05) reduced in LPS‐treated rats compared to the vehicle‐treated rats. This reduction was prevented by pre‐treatment of rats with glibenclamide (GLB), a selective inhibitor of KATP channels.
GLB administration did not affect the MAP in vehicle‐treated rats but produced an increase of MAP in rats treated with LPS.
Cromakalim (CRK), a selective KATP channel opener, produced a reduction of MAP that was significantly (P<0.05) higher in LPS‐ than in vehicle‐treated rats. In contrast, the hypotension induced by glyceryl trinitrate (GTN) in LPS‐treated rats was not distinguishable from that produced in vehicle‐treated rats.
Experiments in vitro were conducted on aorta rings collected from rats treated with vehicle or LPS 24 h before sacrifice. The concentration‐dependent curve to PE was statistically (P<0.005) reduced in aorta rings collected from LPS‐ compared to vehicle‐treated rats. This difference was totally abolished by tetraethylammonium (TEA), a non‐selective inhibitor of K+ channels.
CRK produced a relaxation of PE precontracted aorta rings higher in rings from LPS‐ than in vehicle‐treated rats. GLB inhibited CRK‐induced relaxation in both tissues, abolishing the observed differences.
In conclusion, our results indicate an involvement of KATP channels to the hyporesponsiveness of vascular tissue after 24 h from a single injection of LPS in rats. We can presume an increase in the activity of KATP channels on vascular smooth muscle cells but we cannot exclude an increase of KATP channel number probably due to the gene expression activation.

British Journal of Pharmacology (1999) 127, 1447–1453; doi:10.1038/sj.bjp.0702666
Evidence for two different P2X‐receptors mediating vasoconstriction of Ap5A and Ap6A in the isolated perfused rat kidney
Authors: Van Der Giet Markus , Cinkilic Okan , Jankowski Joachim , Tepel Martin , Zidek Walter , Schlüter Hartmut 
Published: January 2005

The activation of various P2‐receptor subtypes in rat renal vasculature by P1, P5‐diadenosine pentaphosphate (Ap5A) and P1, P6‐diadenosine hexaphosphate (Ap6A) were studied by measuring their effects on perfusion pressure during continuous perfusion in a rat isolated perfused kidney.
Permanent perfusion with Ap5A and Ap6A elicited both a transient and sustained vasoconstriction with both vasoconstrictions to be different: the transient vasoconstriction can be elicited with concentrations 10 nM, whereas the sustained vasoconstriction is observed with concentrations 1 nM.
Ap5A and Ap6A act via the same receptors as α,β‐methylene ATP (α,β‐meATP).
The rank order of potency for transient vasconstriction was α,β‐meATP=Ap5A>Ap6A>β,γ‐meATP, and for sustained vasoconstriction α,β‐meATP=Ap5A>β,γ‐meATP Ap6A.
Suramin, a non‐selective P2‐receptor antagonist, and pyridoxal‐phosphate‐6‐azophenyl‐2;4‐disulphonic acid (PPADS) a highly selective P2X‐receptor antagonist antagonized both the transient and the sustained vasoconstriction.
Taken together the results of the agonist profile of Ap5A and Ap6A and comparing its findings to literature it can be demonstrated that the transient but not the sustained vasoconstriction is mediated via the P2X1‐receptor which is present in rat renal vasculature.
It is demonstrated that the agonist profile of the sustained vasoconstriction induced by Ap5A and Ap6A does not fit to any currently known P2X‐ or P2Y‐receptor subtype.
We conclude a yet unidentified P2X‐receptor or chimeric P2X‐receptor may contribute to the effects on rat renal vasculature produced by Ap5A and Ap6A and which may play an important role in glomerular perfusion pressure and blood pressure control.

British Journal of Pharmacology (1999) 127, 1463–1469; doi:10.1038/sj.bjp.0702667
Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits
Authors: Verd Joan C , Peris Cristina , Alegret Marta , Díaz Cristina , Hernández Gonzalo , Vázquez Manuel , Adzet Tomás , Laguna Juan C , Sánchez Rosa M 
Published: January 2005

The effects of atorvastatin (3 mg kg−1) and simvastatin (3 mg kg−1) on hepatic enzyme activities involved in very low density lipoprotein metabolism were studied in coconut oil/cholesterol fed rabbits.
Plasma cholesterol and triglyceride levels increased 19 and 4 fold, respectively, after 7 weeks of feeding.
Treatment with statins during the last 4 weeks of feeding abolished the progression of hypercholesterolaemia and reduced plasma triglyceride levels.
3‐Hydroxy‐3‐methyl‐glutaryl Coenzyme A reductase, acyl‐coenzyme A:cholesterol acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities were not affected by drug treatment. Accordingly, hepatic free cholesterol, cholesteryl ester and triglyceride content were not modified.
Simvastatin treatment caused an increase (72%) in lipoprotein lipase activity without affecting hepatic lipase activity.
Atorvastatin caused a reduction in hepatic phospholipid content and a compensatory increase in CTP:phosphocholine cytidylyl transferase activity.
The results presented in this study suggest that, besides the inhibitory effect on 3‐hydroxy‐3‐methyl‐glutaryl Coenzyme A reductase, simvastatin and atorvastatin may have additional effects that contribute to their triglyceride‐lowering ability.

British Journal of Pharmacology (1999) 127, 1479–1485; doi:10.1038/sj.bjp.0702668