bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic AMP‐dependent inhibition of human neutrophil oxidative activity by substituted 2‐propynylcyclohexyl adenosine A2A receptor agonists
Authors: Sullivan Gail W , Rieger Jayson M , Michael Scheld W , Macdonald Timothy L , Linden Joel 
Published: January 2005

Novel 2‐propynylcyclohexyl‐5′‐N‐ehtylcarboxamidoadenosines, trans‐substituted in the 4‐position of the cyclohexyl ring, were evaluated in binding assays to the four subtypes of adenosine receptors (ARs). Two esters, 4‐{3‐[6‐amino‐9‐(5‐ethylcarbamoyl‐3,4‐dihydroxy‐tetrahydro‐furan‐2‐yl)‐9H‐purin‐2‐yl]‐prop‐2‐ynyl}‐cyclohexanecarboxylic acid methyl ester (ATL146e) and acetic acid 4‐{3‐[6‐amino‐9‐(5‐ethylcarbamoyl‐3, 4‐dihydroxy‐tetrahydro‐furan ‐2‐yl)‐9H‐purin‐2‐yl] ‐prop‐2‐ynyl}‐cyclohexylmethyl ester (ATL193) were >50×more potent than 2‐[4‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS21680) for human A2A AR binding. Human A2A AR affinity for substituted cyclohexyl‐propynyladenosine analogues was inversely correlated with the polarity of the cyclohexyl side chain. There was a comparable order of potency for A2A AR agonist stimulation of human neutrophil [cyclic AMP]i, and inhibition of the neutrophil oxidative burst. ATL146e and CGS21680 were ∼equipotent agonists of human A3 ARs.
We measured the effects of selective AR antagonists on agonist stimulated neutrophil [cyclic AMP]i and the effect of PKA inhibition on A2A AR agonist activity. ATL193‐stimulated neutrophil [cyclic AMP]i was blocked by antagonists with the potency order: ZM241385 (A2A‐selective)>MRS1220 (A3‐selective)>>N‐(4‐Cyano‐phenyl)‐2‐[4‐(2,6‐dioxo‐1,3‐dipropyl‐2,3,4,5,6,7‐hexahydro‐1H‐purin‐8‐yl)‐phenoxy]‐acetamide (MRS1754; A2B‐selective) ∼amp; 8‐(N‐methylisopropyl)amino‐N6‐(5′‐endohydroxy‐endonorbornyl)‐9‐methyladenine (WRC0571; A1‐selective). The type IV phosphodiesterase inhibitor, rolipram (100 nM) potentiated ATL193 inhibition of the oxidative burst, and inhibition by ATL193 was counteracted by the PKA inhibitor H‐89.
The data indicate that activation of A2AARs inhibits neutrophil oxidative activity by activating [cyclic AMP]i/PKA.

British Journal of Pharmacology (2001) 132, 1017–1026; doi:10.1038/sj.bjp.0703893
Ligand internalization and recycling by human recombinant somatostatin type 4 (h sst4) receptors expressed in CHO‐K1 cells
Authors: Smalley K S M , Koenig J A , Feniuk W , Humphrey P P A 
Published: January 2005

There is controversy as to whether somatostatin sst4 receptors internalize. In this study, CHO‐K1 cells expressing human sst4 receptor (CHOsst4 cells) cells internalized [125I]‐[11Tyr]‐SRIF in a time‐dependent manner, reaching a steady state at 60 min (1.4±0.1×104 molecules internalized per cell). Internalization was blocked by hypertonic sucrose (0.5 M), ATP depletion or by decreasing the temperature to 4°C.
Internalization of [125I]‐[11Tyr]‐SRIF was also inhibited (pIC50 values) by increasing concentrations of SRIF (7.74), L‐362855 (6.27) and NNC‐296100 (6.50) with pIC50 values approximately 10 fold lower than those obtained for inhibition of [125I]‐[11Tyr]‐SRIF binding to membrane homogenates.
Internalized ligand recycled rapidly to the extracellular media (t1/2 3.9±0.7 min) with only 6.8±0.6% of internalized radioactivity remaining in the cell after 45 min.
Confocal microscopy of permeabilized, HA‐epitope tagged CHOsst4 cells labelled with a Cy‐3 conjugated antibody revealed little internal immunostaining after SRIF (1 μM) treatment, consistent with the small proportion of receptors (3.5%) estimated to be internalized by radioimmunoassay.
In summary, CHOsst4 cells internalized [125I]‐[11Tyr]‐SRIF in a clathrin‐ and ATP‐dependent manner with subsequent rapid recycling to the extracellular medium. Rapid receptor recycling and the consequent low proportion of receptors internalized at any one time may explain the inability to visualize internalized receptors by confocal microscopy. It seems unlikely therefore that the marked receptor desensitization observed in CHOsst4 cells following SRIF treatment can be accounted for by a decrease in cell surface receptor expression.

British Journal of Pharmacology (2001) 132, 1102–1110; doi:10.1038/sj.bjp.0703896
Potentiation of the antinociceptive effect of clomipramine by a 5‐ht1A antagonist in neuropathic pain in rats
Authors: Ardid D , Alloui A , Brousse G , Jourdan D , Picard P , Dubray C , Eschalier A 
Published: January 2005

The benefit of antidepressant treatment in human neuropathic pain is now well documented, but the effect is limited and slow to appear. It has been demonstrated that the association of a 5‐HT1A antagonist and a serotoninergic antidepressant reduced the delay of action and increases the thymoanaleptic effect of the drug.
The purpose of this work was to evaluate the combination of an antidepressant and a 5‐HT1A antagonist in animal models of chronic neuropathic pain. We studied the antinociceptive effect of the co‐administration of clomipramine and a 5‐HT1A antagonist (WAY 100,635) in a pain test applied in normal rats and in two models of neurogenic sustained pain (mononeuropathic and diabetic rats).
The results show an increase in the antinociceptive effect of acutely injected clomipramine due to WAY 100,635 in these models, which is majored when the two drugs are repeatedly injected. The 5‐HT1A antagonist reduced the delay of onset and increased the maximal antinociceptive effect of clomipramine.
These new findings argue for using the combination of an antidepressant and a 5‐HT1A antagonist in human neuropathic pain therapy.

British Journal of Pharmacology (2001) 132, 1118–1126; doi:10.1038/sj.bjp.0703897
Glucuronide and glucoside conjugation of mycophenolic acid by human liver, kidney and intestinal microsomes
Authors: Shipkova M , Strassburg C P , Braun F , Streit F , Gröne H‐J , Armstrong V W , Tukey R H , Oellerich M , Wieland E 
Published: January 2005

Mycophenolic acid (MPA) is primarily metabolized to a phenolic glucuronide (MPAG) as well as to two further minor metabolites: an acyl glucuronide (AcMPAG) and a phenolic glucoside (MPAG1s). This study presents investigations of the formation of these metabolites by human liver (HLM), kidney (HKM), and intestinal (HIM) microsomes, as well as by recombinant UDP‐glucuronosyltransferases.
HLM (n=5), HKM (n=6), HIM (n=5) and recombinant UGTs were incubated in the presence of either UDP‐glucuronic acid or UDP‐glucose and various concentrations of MPA. Metabolite formation was followed by h.p.l.c.
All microsomes investigated formed both MPAG and AcMPAG. Whereas the efficiency of MPAG formation was greater with HKM compared to HLM, AcMPAG formation was greater with HLM than HKM. HIM showed the lowest glucuronidation efficiency and the greatest interindividual variation. The capacity for MPAGls formation was highest in HKM, while no glucoside was detected with HIM.
HKM produced a second metabolite when incubated with MPA and UDP‐glucose, which was labile to alkaline treatment. Mass spectrometry of this metabolite in the negative ion mode revealed a molecular ion of m/z 481 compatible with an acyl glucoside conjugate of MPA.
All recombinant UGTs investigated were able to glucuronidate MPA with KM values ranging from 115.3 to 275.7 μM l−1 and Vmax values between 29 and 106 pM min−1 mg protein−1.
Even though the liver is the most important site of MPA glucuronidation, extrahepatic tissues particularly the kidney may play a significant role in the overall biotransformation of MPA in man. Only kidney microsomes formed a putative acyl glucoside of MPA.

British Journal of Pharmacology (2001) 132, 1027–1034; doi:10.1038/sj.bjp.0703898
Effects of KRN2391 on ionic currents in rabbit femoral arterial myocytes
Authors: Muraki Katsuhiko , Sasaoka Akiko , Watanabe Minoru , Imaizumi Yuji 
Published: January 2005

The effects of KRN2391, an ATP‐sensitive K+ channel opener (KCO) which also acts as a nitrate, on ionic membrane currents in rabbit femoral arterial myocytes were examined.
Under whole‐cell clamp conditions where cells were superfused with physiological salts solution containing 5.9 mM K+, KRN2391 elicited an outward current at a holding potential of −30 mV. KRN2391‐induced current had a reversal potential of −78 mV and was abolished by glibenclamide (glib). KRN2391 was approximately 25 times more potent than nicorandil to activate an ATP‐sensitive K+ current (IKATP). On the other hand, 10 μM KRN2391 did not affect either voltage‐dependent Ca2+ or delayed rectifier K+ channel currents.
In the inside‐out patch configuration, KRN2391 activated 47 pS K+ channels in the presence of nucleotide diphosphates (NDPs) under the symmetrical 140 mM K+ conditions. Glib and intracellular ATP reversibly inhibited the activity of the 47 pS K+ channels.
The 47 pS K+ channels activated by KRN2391 are similar in their conductance and other properties to NDP‐sensitive K+ channels (KNDP channels) described in other smooth muscles and the cloned channels. KRN2391 is a potent activator of the 47 pS K+ channels and the activation can contribute to the KRN2391‐induced vasodilation in arterial muscles.

British Journal of Pharmacology (2001) 132, 1154–1160; doi:10.1038/sj.bjp.0703903
Alteration of excitation‐contraction coupling mechanism in extensor digitorum longus muscle fibres of dystrophic mdx mouse and potential efficacy of taurine
Authors: De Luca Annamaria , Pierno Sabata , Liantonio Antonella , Cetrone Michela , Camerino Claudia , Simonetti Simonetta , Papadia Francesco , Camerino Diana Conte 
Published: January 2005

No clear data is available about functional alterations in the calcium‐dependent excitation‐contraction (e‐c) coupling mechanism of dystrophin‐deficient muscle of mdx mice.
By means of the intracellular microelectrode ‘point’ voltage clamp method, we measured the voltage threshold for contraction (mechanical threshold; MT) in intact extensor digitorum longus (EDL) muscle fibres of dystrophic mdx mouse of two different ages: 8–12 weeks, during the active regeneration of hind limb muscles, and 6–8 months, when regeneration is complete.
The EDL muscle fibres of 8–12‐week‐old wildtype animals had a more negative rheobase voltage (potential of equilibrium for contraction‐ and relaxation‐related calcium movements) with respect to control mice of 6–8 months. However, at both ages, the EDL muscle fibres of mdx mice contracted at more negative potentials with respect to age‐matched controls and had markedly slower time constants to reach the rheobase.
The in vitro application of 60 mM taurine, whose normally high intracellular muscle levels play a role in e‐c coupling, was without effect on 6–8‐month‐old wildtype EDL muscle, while it significantly ameliorated the MT of mdx mouse.
HPLC determination of taurine content at 6–8 months showed a significant 140% rise of plasma taurine levels and a clear trend toward a decrease in amino acid levels in hind limb muscles, brain and heart, suggesting a tissue difficulty in retaining appropriate levels of the amino acid.
The data is consistent with a permanent alteration of e‐c coupling in mdx EDL muscle fibres. The alteration could be related to the proposed increase in intracellular calcium, and can be ameliorated by taurine, suggesting a potential therapeutic role of the amino acid.

British Journal of Pharmacology (2001) 132, 1047–1054; doi:10.1038/sj.bjp.0703907
Effects of the oestrous cycle and gender on acute vasodilatory responses of isolated pressurized rat mesenteric arteries to 17 β‐oestradiol
Authors: Shaw Linda , Taggart Michael , Austin Clare 
Published: January 2005

The influence of the oestrous cycle and gender on responses of isolated pressurized mesenteric arteries to acute 17 β‐oestradiol was investigated.
All vessels, pre‐contracted with 60 mM KCl or 10 μM U46619 (9,11 dideoxy‐11α, 9α‐epoxy methano‐prostaglandin), exhibited concentration‐dependent vasodilatory responses to 17 β‐oestradiol (3–30 μM). The largest responses were seen in vessels from female rats in pro‐oestrous (38.9±5.4% U46619 max and 63.1±4.0% KCl max for 30 μM oestradiol), the smallest from animals in di‐oestrous (20.1±3.7% U46619 and 50.1±4.5% KCL–both P<0.05 cf pro‐oestrous (all n=8)). Responses of vessels from male rats were similar to those from pro‐oestrous rats (41.5±9.1% U46619 (n=10) and 54.9±2.9% KCl (n =8)).
All responsees were unaffected by inhibition of nitric oxide synthase (NOS).
Female rats in pro‐oestrous had the highest plasma concentrations of 17 β‐oestradiol and testosterone (40.76±4.73 pg ml−1 and 0.29±0.05 ng ml−1 respectively (n=8)) while those in di‐oestrous had the lowest (15.24±3.94 pg ml−1 for oestradiol and 0.08±0.03 ng ml−1 for testosterone (n=8)). In male rats the concentration of oestrogen was 10.29±1.21 pg ml−1 (n=7) while that of testosterone was 3.15±0.36 ng ml−1 (n=7).
Incubation of arteries isolated from male rats and from female rats in pro‐oestrous and di‐oestrous with testosterone (1 μM, 3 h) significantly enhanced the subsequent vasodilatory responses to acute 17 β‐oestradiol. Following incubation, the responses to 17 β‐oestradiol were similar in all groups.
These observations suggest that gender and the oestrous cycle may influence the vascular responses to acute 17 β‐oestradiol administration.

British Journal of Pharmacology (2001) 132, 1055–1062; doi:10.1038/sj.bjp.0703908
Mitochondrial involvement in cocaine‐treated rat hepatocytes: effect of N‐acetylcysteine and deferoxamine
Authors: Zaragoza Asunción , Díez‐Fernández Carmen , Alvarez Alberto M , Andrés David , Cascales María 
Published: January 2005

The cytotoxicity of cocaine (0–1000 μM), was studied on parameters related to the mitochondrial role and the cascade of events that lead to apoptosis in hepatocyte cultures from phenobarbitone (PB) pretreated rats.
Cytotoxicity was dose‐dependent and LDH leakage was significantly enhanced above 100 μM cocaine. Apoptosis was visualized by DNA fragmentation on agarose gel, and appeared at 50 and 100 μM cocaine. Cocaine induced biphasic changes in mitochondrial transmembrane potential and significantly increased the mitochondrial release of cytochrome c, the caspase‐3 like DEVDase activity and the level of 20 kDa subunit, a product of pro‐caspase‐3 cleavage.
The protective effect of N‐acetylcysteine (NAC) and deferoxamine (DFO) on all these parameters confirmed the involvement of oxygen radicals in cocaine‐induced necrosis/apoptosis.
We conclude: first, that the biphasic changes recorded in mitochondrial inner membrane potential by the effect of cocaine, were parallel to apoptosis; second, that caspase‐3 activity and cleavage to it p20 subunit increased sharply in parallel to the translocation of cytochrome c from mitochondria to cytosol; and third, that the antioxidants, NAC or DFO exerted a noticeable protective role in counteracting the cytotoxicity of cocaine, these effects being more pronounced in the case of DFO than NAC.
These findings demonstrate that cocaine cytotoxicity involves mitochondrial damage.

British Journal of Pharmacology (2001) 132, 1063–1070; doi:10.1038/sj.bjp.0703909
The GR127935‐sensitive 5‐HT1 receptors mediating canine internal carotid vasoconstriction: resemblance to the 5‐HT1B, but not to the 5‐HT1D or 5‐ht1F, receptor subtype
Authors: Centurión David , Sánchez‐López Araceli , De Vries Peter , Saxena Pramod R , Villalón Carlos M 
Published: January 2005

This study has further investigated the pharmacological profile of the GR127935‐sensitive 5‐HT1 receptors mediating vasoconstriction in the internal carotid bed of anaesthetized vagosympathectomized dogs.
One‐minute intracarotid infusions of the agonists 5‐hydroxytryptamine (5‐HT; 0.1–10 μg min−1; endogenous ligand) and sumatriptan (0.3–10 μg min−1; 5‐HT1B/1D), but not PNU‐142633 (1–1000 μg min−1; 5‐HT1D) or LY344864 (1–1000 μg min−1; 5‐ht1F), produced dose‐dependent decreases in internal carotid blood flow without changing blood pressure or heart rate.
The responses to 5‐HT were apparently resistant to blockade by i.v. administration of the antagonists SB224289 (300 μg kg−1; 5‐HT1B), BRL15572 (300 μg kg−1; 5‐HT1D) or ritanserin (100 μg kg−1; 5‐HT2). In contrast, the responses to sumatriptan were antagonized by SB224289, but not by BRL15572.
In the animals receiving SB224289, but not those receiving BRL15572, the subsequent administration of ritanserin abolished the 5‐HT‐induced vasoconstriction and unmasked a vasodilator component. Similarly, in ritanserin‐treated animals, the subsequent administration of SB224289, but not BRL15572, completely blocked the 5‐HT‐induced vasoconstriction, revealing vasodilatation. In animals receiving initially BRL15572, the subsequent administration of SB224289 did not affect (except at 10 μg min−1) the vasoconstrictor responses to 5‐HT.
Notably, in animals pretreated with 1000 μg kg−1 of mesulergine, a 5‐HT2/7 receptor antagonist, 5‐HT produced a dose‐dependent vasoconstriction, which was practically abolished by SB224289. After BRL15572, no further blockade was produced and the subsequent administration of ritanserin was similarly inactive.
These results suggest that the GR127935‐sensitive 5‐HT1 receptors mediating canine internal carotid vasoconstriction resemble the 5‐HT1B but not the 5‐HT1D or 5‐ht1F, receptor subtype.

British Journal of Pharmacology (2001) 132, 991–998; doi:10.1038/sj.bjp.0703913
Evidence for 5‐HT1B/1D and 5‐HT2A receptors mediating constriction of the canine internal carotid circulation
Authors: Centurión David , Ortiz Mario I , Sánchez‐López Araceli , De Vries Peter , Saxena Pramod R , Villalón Carlos M 
Published: January 2005

The present study has investigated the preliminary pharmacological profile of the receptors mediating vasoconstriction to 5‐hydroxytryptamine (5‐HT) in the internal carotid bed of vagosympathectomised dogs.
One minute intracarotid infusions of the agonists 5‐HT (0.1–10 μg min−1), sumatriptan (0.3–10 μg min−1; 5‐HT1B/1D), 5‐methoxytryptamine (1–100 μg min−1; 5‐HT1, 5‐HT2, 5‐HT4, 5‐ht6 and 5‐HT7) or DOI (0.31–10 μg min−1; 5‐HT2), but not 5‐carboxamidotryptamine (0.01–0.3 μg min−1; 5‐HT1, 5‐ht5A and 5‐HT7), 1‐(m‐chlorophenyl)‐biguanide (mCPBG; 1–1000 μg min−1; 5‐HT3) or cisapride (1–1000 μg min−1; 5‐HT4), resulted in dose‐dependent decreases in internal carotid blood flow, without changing blood pressure or heart rate.
The vasoconstrictor responses to 5‐HT, which remained unaffected after saline, were resistant to blockade by i.v. administration of the antagonists ritanserin (100 μg kg−1; 5‐HT2A/2B/2C) in combination with tropisetron (3000 μg kg−1; 5‐HT3/4) or the cyclo‐oxygenase inhibitor, indomethacin (5000 μg kg−1), but were abolished by the 5‐HT1B/1D receptor antagonist, GR127935 (30 μg kg−1). Interestingly, after administration of GR127935, the subsequent administration of ritanserin unmasked a dose‐dependent vasodilator component. GR127935 or saline did not practically modify the vasoconstrictor effects of 5‐MeO‐T. In animals receiving GR127935, the subsequent administration of ritanserin abolished the vasoconstrictor responses to 5‐MeO‐T unmasking a dose‐dependent vasodilator component.
The vasoconstriction induced by sumatriptan was antagonized by GR127935, but not by ritanserin. Furthermore, ritanserin (100 μg kg−1) or ketanserin (100 μg kg−1; 5‐HT2A), but not GR127935, abolished DOI‐induced vasoconstrictor responses.
The above results suggest that 5‐HT‐induced internal carotid vasoconstriction is predominantly mediated by 5‐HT1B/1D and 5‐HT2A receptors.

British Journal of Pharmacology (2001) 132, 983–990; doi:10.1038/sj.bjp.0703914
The role of several α1‐ and α2‐adrenoceptor subtypes mediating vasoconstriction in the canine external carotid circulation
Authors: Willems Edwin W , Valdivia Luis Felipe , Saxena Pramod R , Villalón Carlos M 
Published: January 2005

It has recently been shown that both α1‐ and α2‐adrenoceptors mediate vasoconstriction in the canine external carotid circulation. The present study set out to identify the specific subtypes (α1A, α1B and α1D as well as α2A, α2B and α2C) mediating the above response.
Consecutive 1 min intracarotid infusions of phenylephrine (α1‐adrenoceptor agonist) and BHT933 (α2‐adrenoceptor agonist) produced dose‐dependent decreases in external carotid blood flow, without affecting mean arterial blood pressure or heart rate.
The responses to phenylephrine were selectively antagonized by the antagonists, 5‐methylurapidil (α1A) or BMY7378 (α1D), but not by L‐765,314 (α1B), BRL44408 (α2A), imiloxan (α2B) or MK912 (α2C). In contrast, only BRL44408 or MK912 affected the responses to BHT933.
The above results support our contention that mainly the α1A, α1D, α2A and α2C‐adrenoceptor subtypes mediate vasoconstriction in the canine external carotid circulation.

British Journal of Pharmacology (2001) 132, 1292–1298; doi:10.1038/sj.bjp.0703915
Interaction of stilbene disulphonates with cloned KATP channels
Authors: Proks Peter , Jones Phillippa , Ashcroft Frances M 
Published: January 2005

In this study, we tested the effects of the stilbene disulphonates DIDS and SITS on three different types of cloned KATP channel (Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.2ΔC) heterologously expressed in Xenopus oocytes, with the aim of identifying the part of the channel which is involved in mediating disulphonate inhibition.
We found that the inhibitory site(s) for these drugs lies within the Kir6.2 subunit of the channel, although its properties are further modulated by the sulphonylurea (SUR) subunit. In particular, SUR2A reduces both the rate and extent of block, by impairing the ability of DIDS binding to produce channel closure.
The disulphonate‐binding site interacts with the ATP inhibitory site on Kir6.2 because ATP is able to protect against irreversible channel inhibition by disulphonates. This effect is not mimicked by tolbutamide (at a concentration that interacts with Kir6.2) and is abolished by mutations that render the channel ATP insensitive.
A number of point mutations in both the N and C termini of Kir6.2 reduced the extent and reversibility of channel inhibition by SITS. The results are consistent with the idea that residue C42 of Kir6.2 is likely to be involved in covalently linking of SITS to the channel.
Other types of Kir channel (Kir1.1, Kir2.1 and Kir4.1) were also irreversibly blocked by DIDS, suggesting that these channels may share common binding sites for these stilbene disulphonates.

British Journal of Pharmacology (2001) 132, 973–982; doi:10.1038/sj.bjp.0703916
Pharmacological differences between the human and rat vanilloid receptor 1 (VR1)
Authors: McIntyre Peter , McLatchie Linda M , Chambers Anne , Phillips Elsa , Clarke Melanie , Savidge Jonathan , Toms Christy , Peacock Marcus , Shah Kirti , Winter Janet , Weerasakera Natasha , Webb Mike , Rang Humphrey P , Bevan Stuart , James Iain F 
Published: January 2005

Vanilloid receptors (VR1) were cloned from human and rat dorsal root ganglion libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (CHO) cells.
Both rat and human VR1 formed ligand gated channels that were activated by capsaicin with similar EC50 values. Capsaicin had a lower potency on both channels, when measured electrophysiologically in oocytes compared to CHO cells (oocytes: rat=1.90±0.20 μM; human=1.90±0.30 μM: CHO cells: rat=0.20±0.06 μM; human=0.19±0.08 μM).
In CHO cell lines co‐expressing either rat or human VR1 and the calcium sensitive, luminescent protein, aequorin, the EC50 values for capsaicin‐induced responses were similar in both cell lines (rat=0.35±0.06 μM, human=0.53±0.03 μM).
The threshold for activation by acidic solutions was lower for human VR1 channels than that for rat VR1 (EC50 pH 5.49±0.04 and pH 5.78±0.09, respectively).
The threshold for heat activation was identical (42°C) for rat and human VR1.
PPAHV was an agonist at rat VR1 (EC50 between 3 and 10 μM) but was virtually inactive at the human VR1 (EC50>10 μM).
Capsazepine and ruthenium red were both more potent at blocking the capsaicin response of human VR1 than rat VR1.
Capsazepine blocked the human but not the rat VR1 response to low pH. Capsazepine was also more effective at inhibiting the noxious heat response of human than of rat VR1.

British Journal of Pharmacology (2001) 132, 1084–1094; doi:10.1038/sj.bjp.0703918