bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of caffeine on ATP‐sensitive K+ channels in smooth muscle cells from pig urethra
Authors: Teramoto Noriyoshi , Yunoki Takakazu , Tanaka Kiyoshi , Takano Makoto , Masaki Ichiro , Yonemitsu Yoshikazu , Sueishi Katsuo , Ito Yushi 
Published: January 2005

The effects of caffeine on both levcromakalim‐induced macroscopic and unitary currents in pig proximal urethra were investigated by the use of patch‐clamp techniques (conventional whole‐cell configuration and cell‐attached configuration). The effects of caffeine were also examined on currents in inside‐out patches of COS7 cells expressing carboxy terminus truncated inwardly rectifying K+ channel (Kir6.2) subunits (i.e. Kir6.2ΔC36) which form ATP‐sensitive K+ channels (KATP channels).
In conventional whole‐cell configuration, the levcromakalim (100 μM)‐induced inward current (symmetrical 140 mM K+ conditions) was inhibited by caffeine (1 mM) at a holding potential of −50 mV. In contrast, ryanodine (10 μM) caused no significant inhibitory effect on the gradual decay of the levcromakalim‐induced current at −50 mV.
The amplitude of the 30 μM levcromakalim‐induced current was enhanced by 3‐isobutyl‐1‐methylxanthine (IBMX, 100 μM).
In cell‐attached configuration, the levcromakalim‐induced K+ channel openings were inhibited by subsequent application of 10 mM caffeine, decreasing the channel open probability at −50 mV.
Reverse transcriptase‐polymerase chain reaction (RT–PCR) analysis revealed the presence of Kir6.2 transcript in pig urethra.
Caffeine (3 mM) inhibited the channel activity of Kir6.2ΔC36 expressed in COS7 cells (3 mM caffeine, 65±6%, n=4; 10 mM caffeine, 29±2%, n=4).
These results suggest that caffeine can inhibit the activity of KATP channels through a direct blocking effect on the pore‐forming Kir subunit.

British Journal of Pharmacology (2000) 131, 505–513; doi:10.1038/sj.bjp.0703586
Airway reactivity, inflammatory cell influx and nitric oxide in guinea‐pig airways after lipopolysaccharide inhalation
Authors: Toward Toby J , Broadley Kenneth J 
Published: January 2005

The aim of this study was to investigate the relationship between airway reactivity, leukocyte influx and nitric oxide (NO), in conscious guinea‐pigs after aerosolized lipopolysaccharide (LPS) exposure.
Inhaled histamine (1 mM, 20 s), causing no bronchoconstriction before LPS exposure (30 μg ml−1, 1 h), caused bronchoconstriction at 0.5 and 1 h (P<0.02) after LPS exposure. This airway hyperreactivity (AHR) recovered by 2 h. In contrast, 48 h after LPS exposure, the response from a previously bronchoconstrictor dose of histamine (3 mM, 20 s) was attenuated (P<0.01) i.e. airway hyporeactivity (AHOR).
Investigation of the cellular content of bronchoalveolar lavage fluid (BALF) from these animals revealed a rapid (0.5 h: 691 fold increase) and progressive neutrophil influx after LPS exposure (24 h: 36.3±2.3×106 cells per sample), that subsided 48 h later. Macrophages and eosinophils also time‐dependently increased (0.5 h: 4.6±0.4 and 0.1±0.05; 48 h: 31.0±6.0 and 1.8±0.3×106 cells per sample, respectively) after LPS, compared to vehicle exposure (24 h: neutrophils, eosinophils and macrophages: 0.28±0.19, 0.31±0.04 and 4.96±0.43×106 cells per sample, respectively).
The combined NO metabolites in BALF, after vehicle (1 h), or LPS (1 h: AHR and 48 h: AHOR) exposure, were respectively increased (41%, P<0.01), decreased (47%, P<0.01) and further increased (80%, P<0.001), compared with naïve animals.
Inhaled No‐nitro‐L‐arginine methyl ester (L‐NAME: 1.2 and 12 mM, 15 min), reduced BALF NO metabolites 2 h later, but did not cause AHR to histamine (P>0.05). When L‐NAME inhalation followed LPS, AHR was prolonged from 1 h to at least 4 h (P<0.01).
In summary, aerosolized LPS inhalation caused neutrophil and macrophage airways infiltration, and an early development of AHR followed 48 h later by AHOR to histamine. AHR and AHOR coincided with a respective reduction and elevation in airways NO (metabolites). Thus, NO may aid recovery from AHR, as inhibition of its production prolongs AHR. However, NO deficiency alone is not responsible for LPS‐induced AHR.

British Journal of Pharmacology (2000) 131, 271–281; doi:10.1038/sj.bjp.0703589
Dual modulation by thrombin of the motility of rat oesophageal muscularis mucosae via two distinct protease‐activated receptors (PARs): a novel role for PAR‐4 as opposed to PAR‐1
Authors: Kawabata Atsufumi , Kuroda Ryotaro , Kuroki Naoko , Nishikawa Hiroyuki , Kawai Kenzo 
Published: January 2005

Since protease‐activated receptors (PARs) are distributed throughout the gastrointestinal tract, we investigated the role of PARs in modulation of the motility of the rat oesophageal muscularis mucosae.
Thrombin produced contraction of segments of the upper and lower part of the smooth muscle. Trypsin contracted both the muscle preparations only at high concentrations. SFLLR‐NH2 and TFLLR‐NH2 (PAR‐1‐activating peptides), but not the PAR‐1‐inactive peptide FSLLR‐NH2, evoked a marked contraction. In contrast, the PAR‐2 agonist SLIGRL‐NH2 and the PAR‐4 agonist GYPGKF‐NH2 caused no or only a negligible contraction.
In oesophageal preparations precontracted with carbachol, thrombin produced a dual action i.e. relaxation followed by contraction. TFLLR‐NH2 further contracted the precontracted preparations with no preceding relaxation. GYPGKF‐NH2, but not the inactive peptide GAPGKF‐NH2, produced marked relaxation. Trypsin or SLIGRL‐NH2 caused no relaxation.
The PAR‐1‐mediated contraction was completely abolished in Ca2+‐free medium and considerably attenuated by nifedipine (1 μM) and in a low Na+ medium. The PAR‐4‐mediated relaxation was resistant to tetrodotoxin (10 μM), apamin (0.1 μM), charybdotoxin (0.1 μM), L‐NG‐nitroarginine methyl ester (100 μM), indomethacin (3 μM), propranolol (5 μM) or adenosine 3′,5′‐cyclic monophosphorothioate, 8‐bromo, Rp‐isomer (30 μM).
Thus, thrombin plays a dual role in modulating the motility of the oesophageal muscularis mucosae, producing contraction via PAR‐1 and relaxation via PAR‐4. The PAR‐1‐mediated effect appears to occur largely through increased Na+ permeability followed by activation of L‐type Ca2+ channels and subsequent influx of extracellular Ca2+. Our data could provide evidence for a novel role of PAR‐4 as opposed to PAR‐1, although the underlying mechanisms are still open to question.

British Journal of Pharmacology (2000) 131, 578–584; doi:10.1038/sj.bjp.0703590
Differences in the effects of urinary incontinence agents S‐oxybutynin and terodiline on cardiac K+ currents and action potentials
Authors: Jones Stephen E , Shuba Lesya M , Zhabyeyev Pavel , McCullough John R , McDonald Terence F 
Published: January 2005

The cardiac electrophysiological effects of S‐oxybutynin, a single‐enantiomer drug under evaluation for the management of urinary incontinence, have been investigated and compared with those of terodiline, an incontinence agent withdrawn following reports of QT lengthening and ventricular tachyarrhythmia. Membrane currents were recorded from whole‐cell configured guinea‐pig and rabbit ventricular myocytes, and action potentials were recorded from guinea‐pig and rabbit papillary muscles.
L‐type Ca2+ current (ICa,L), rapidly‐activating K+ current (IKr) and slowly‐activating K+ current (IKs) were unaffected by submicromolar S‐oxybutynin and inhibited by higher concentrations; IC50 values were 17.8 μM for ICa,L, 12 μM for IKr, and 41 μM for IKs. Terodiline IC50 values were somewhat lower for ICa,L (15.2 μM) and IKs (30 μM), but 24 fold lower in the case of IKr (0.5 μM).
The durations of action potentials in guinea‐pig and rabbit papillary muscles driven at 1 Hz were unaffected or moderately shortened by 0.1–100 μM S‐oxybutynin, but lengthened by terodiline. Terodiline (10 μM) also depressed maximal upstroke velocity.
The action potential plateau shortened by an average of 23% when control rabbit papillary muscles were driven at 0.4 Hz instead of 1 Hz. Plateau shortening was significantly smaller in the presence of drugs (30 μM S‐oxybutynin, 3 and 30 μM terodiline), suggesting that they suppress the transient outward current (Ito) involved in rate‐dependent shortening. In experiments on rabbit ventricular myocytes, 3 and 30 μM S‐oxybutynin inhibited Ito by 9±2% and 35±3%, respectively, whereas 3 and 30 μM terodiline inhibited the current by 31±3% and 87±3%, respectively.
The results indicate that S‐oxybutynin has relatively weak non‐specific effects on cardiac ion channels, and that clinically relevant submicromolar concentrations are unlikely to have terodiline‐like proarrhythmic actions on the myocardium.

British Journal of Pharmacology (2000) 131, 245–254; doi:10.1038/sj.bjp.0703595
Influence of β‐adrenoceptor tone on the cardioprotective efficacy of adenosine A1 receptor activation in isolated working rat hearts
Authors: Ford William R , Jugdutt Bodh I , Lopaschuk Gary D , Schulz Rick , Clanachan Alexander S 
Published: January 2005

This study investigated the role of β‐adrenoceptors in the cardioprotective and metabolic actions of adenosine A1 receptor stimulation.
Isolated paced (300 beats min−1) working rat hearts were perfused with Krebs‐Henseleit solution containing 1.2 mM palmitate. Left ventricular minute work (LV work), O2 consumption and rates of glycolysis and glucose oxidation were measured during reperfusion (30 min) following global ischaemia (30 min) as well as during aerobic conditions.
Relative to untreated hearts, N6‐cyclohexyladenosine (CHA, 0.5 μM) improved post‐ischaemic LV work (158%) and reduced glycolysis and proton production (53 and 42%, respectively). CHA+propranolol (1 μM) had similar beneficial effects, while propranolol alone did not affect post‐ischaemic LV work or glucose metabolism. Isoprenaline (10 nM) impaired post‐ischaemic function and after 25 min ischaemia recovery was comparable with 30 min ischaemia in untreated hearts (41 and 53%, respectively). Relative to isoprenaline alone, CHA+isoprenaline improved recovery of LV work (181%) and reduced glycolysis and proton production (64 and 60%, respectively).
In aerobic hearts, CHA, propranolol or CHA+propranolol had no effect on LV work or glucose oxidation. Glycolysis was inhibited by CHA, propranolol and CHA+propranolol (50, 53 and 52%, respectively). Isoprenaline‐induced increases in heart rate, glycolysis and proton production were attenuated by CHA (85, 57 and 53%, respectively).
The cardioprotective efficacy of CHA was unaffected by antagonism or activation of β‐adrenoceptors. Thus, the mechanism of protection by adenosine A1 receptor activation does not involve functional antagonism of β‐adrenoceptors.

British Journal of Pharmacology (2000) 131, 537–545; doi:10.1038/sj.bjp.0703597
Potent stimulation and inhibition of the CFTR Cl− current by phloxine B
Authors: Bachmann Alexander , Russ Ulrich , Waldegger Siegfried , Quast Ulrich 
Published: January 2005

The effects of the fluoresceine derivative, phloxine B, on the Cl− current through the cystic fibrosis transmembrane conductance regulator (CFTR) were examined in Xenopus oocytes expressing human CFTR.
In whole oocytes, the CFTR Cl− current (ICFTR) was activated by superfusion with isobutylmethylxanthine and forskolin. ICFTR was stable during activation and deactivated rapidly upon washout of the activation solution. Phloxine B slowed deactivation and, at high concentrations, inhibited ICFTR weakly.
In excised inside‐out macropatches, ICFTR was activated by the catalytic subunit of protein kinase A (cPKA) and MgATP. Phloxine B (0.01–3 μM), applied after activation, increased ICFTR within 30 s followed by a slow decrease which became dominant at high concentrations. Slowing of deactivation of the CFTR was observed at all concentrations.
The effect of phloxine B after 30 s had a bell‐shaped concentration‐dependence with midpoints at 45 and 1600 nM for the stimulatory and the inhibitory limb, respectively; maximum stimulation was about 1.8 times. The slow inhibitory component, measured after 6 min, occurred with an IC50 value of ∼1 μM.
In the absence of cPKA, phloxine B did not stimulate ICFTR. In the presence of cPKA and MgATP, the effects of phloxine B were more prominent at low (0.02 mM) than at high ATP (2 mM).
The data show that phloxine B modulates ICFTR by increasing channel activity and slowing channel deactivation; at high concentrations inhibition dominates. The effects may be mediated by direct interactions with CFTR from the inside of the cell.

British Journal of Pharmacology (2000) 131, 433–440; doi:10.1038/sj.bjp.0703600
Orphan‐receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin‐1
Authors: Maguire Janet J , Kuc Rhoda E , Davenport Anthony P 
Published: January 2005

We have determined the distribution of receptors for human urotensin‐II (U‐II) in human and rat CNS and peripheral tissues.
In rat, [125I]‐U‐II binding density was highest in the abducens nucleus of brainstem (139.6±14 amol mm−2). Moderate levels were detected in dorsal horn of spinal cord and lower levels in aorta (22.5±6 amol mm−2).
In human tissues density was highest in skeletal muscle and cerebral cortex (∼30 amol mm−2), with lower levels (<15 amol mm−2) in kidney cortex and left ventricle. Little binding was identified in atria, conducting system of the heart and lung parenchyma.
Receptor density was less in human coronary artery smooth muscle (14.6±3 amol mm−2, n=10) than rat aorta with no significant difference between normal and atherosclerotic vessels.
In human skeletal muscle [125I]‐U‐II bound to a single receptor population with KD=0.24±0.17 nM and Bmax=1.97±1.1 fmol mg−1 protein (n=4).
U‐II contracted human coronary, mammary and radial arteries, saphenous and umbilical veins with sub‐nanomolar EC50 values. U‐II was 50 times more potent in arteries and <10 times more potent in veins than endothelin‐1 (ET‐1). The maximum response to U‐II (∼20% of control KCl) was significantly less than to ET‐1 (∼80% KCl). In contrast, in rat aorta, U‐II and ET‐1 were equipotent with similar maximum responses.
This is the first report of high affinity receptors for [125I]‐U‐II in human CNS and peripheral tissues. This peptide produces potent, low efficacy, vasoconstriction in human arteries and veins. These data suggest a potential role for U‐II in human physiology.

British Journal of Pharmacology (2000) 131, 441–446; doi:10.1038/sj.bjp.0703601
Vagal neurotransmission to the ferret lower oesophageal sphincter: inhibition via GABAB receptors
Authors: Smid S D , Blackshaw L A 
Published: January 2005

GABAB receptors modulate the function of the lower oesophageal sphincter (LOS) in vivo by inhibiting neurotransmitter release in the vagal pathway controlling LOS relaxation. We aimed to determine whether this effect was mediated peripherally on vagal motor outflow to the ferret LOS in vitro.
The LOS, with intact vagal innervation, was prepared from adult ferrets and LOS tension measured. Vagal stimulation (0.5–10 Hz, 30 V) evoked a tetrodotoxin‐sensitive, frequency‐dependent relaxation.
Both GABA (3×10−4 M) and (±)baclofen (2×10−4 M) inhibited vagally‐stimulated LOS relaxation. The potent GABAB receptor‐selective agonist 3‐APPA dose‐dependently inhibited vagally‐stimulated LOS relaxation, with an EC50 value of 0.7 μM
Decreased responses following vagal stimulation in the presence of (±)baclofen or 3‐APPA were reversed with the potent GABAB receptor antagonist CGP 62349.
Neither CGP 62349 nor muscimol (GABAA receptor agonist) alone affected LOS responses following vagal stimulation.
Agonists of other G protein‐coupled receptors (clonidine (α2‐adrenoceptor) (5×10−6 M), U50488 (κ opioid) (10−5 M), neuropeptide Y (10−6 M)) did not affect vagally‐mediated LOS relaxation.
The present study supports a discrete presynaptic inhibitory role for GABAB receptors on vagal preganglionic fibres serving inhibitory motorneurones in the ferret LOS.

British Journal of Pharmacology (2000) 131, 624–630; doi:10.1038/sj.bjp.0703602
Pharmacological analysis by HOE642 and KB‐R9032 of the role of Na+/H+ exchange in the endothelin‐1‐induced Ca2+ signalling in rabbit ventricular myocytes
Authors: Wang Hao , Sakurai Kiyoharu , Endoh Masao 
Published: January 2005

The role of Na+/H+ exchange in endothelin‐1 (ET‐1)‐induced increases in Ca2+ transients and cell shortening was studied in rabbit ventricular myocytes loaded with indo‐1/AM. Selective inhibitors of Na+/H+ exchange HOE642 (4‐isopropyl‐3‐methyl‐sulphonylbenzoyl guanidine methanesulphonate) and KB‐R9032 (N‐(4‐isopropyl‐2,2‐dimethyl‐3‐oxo‐3,4‐dihydro‐2H‐benzo‐[1,4]oxazine‐6‐carbonyl) guanidine methanesulphonate) were used as pharmacological tools for the analysis.
ET‐1 at 0.1 nM induced an increase in Ca2+ transients by 45.6%, while it increased cell shortening by 109.6%. For a given increase in cell shortening, the ET‐1‐induced increase in Ca2+ transients was much smaller than that induced by isoprenaline (ISO, 10 nM).
Pretreatment with HOE642 and KB‐R9032 (1 μM) inhibited the increase in cell shortening induced by 0.1 nM ET‐1 by 51 and 65.4%, respectively, without a significant alteration of ET‐1‐induced increase in Ca2+ transients. HOE642 and KB‐R9032 did not affect baseline levels of cell shortening and peak Ca2+ transients, and the effects of ISO (10 nM).
These results indicate that activation of Na+/H+ exchange by ET‐1 may play an important role in the positive inotropic effect and the ET‐1‐induced increase in myofilament Ca2+ sensitivity in rabbit ventricular myocytes.

British Journal of Pharmacology (2000) 131, 638–644; doi:10.1038/sj.bjp.0703608
The bee venom peptide tertiapin underlines the role of IKACh in acetylcholine‐induced atrioventricular blocks
Authors: Drici Milou‐Daniel , Diochot Sylvie , Terrenoire Cécile , Romey Georges , Lazdunski Michel 
Published: January 2005

Acetylcholine (ACh) is an important neuromodulator of cardiac function that is released upon stimulation of the vagus nerve. Despite numerous reports on activation of IKACh by acetylcholine in cardiomyocytes, it has yet to be demonstrated what role this channel plays in cardiac conduction. We studied the effect of tertiapin, a bee venom peptide blocking IKACh, to evaluate the role of IKACh in Langendorff preparations challenged with ACh.
ACh (0.5 μM) reproducibly and reversibly induced complete atrioventricular (AV) blocks in retroperfused guinea‐pig isolated hearts (n=12).
Tertiapin (10 to 300 nM) dose‐dependently and reversibly prevented the AV conduction decrements and the complete blocks in unpaced hearts (n=8, P<0.01).
Tertiapin dose‐dependently blunted the ACh‐induced negative chronotropic response from an ACh‐induced decrease in heart rate of 39±16% in control conditions to 3±3% after 300 nM tertiapin (P=0.01). These effects were not accompanied by any significant change in QT intervals.
Tertiapin blocked IKACh with an IC50 of 30±4 nM with no significant effect on the major currents classically associated with cardiac repolarisation process (IKr, IKs, Ito1, Isus, IK1 or IKATP) or AV conduction (INa and ICa(L)).
In summary, tertiapin prevents dose‐dependently ACh‐induced AV blocks in mammalian hearts by inhibiting IKACh.

British Journal of Pharmacology (2000) 131, 569–577; doi:10.1038/sj.bjp.0703611
Cyclic GMP‐independent relaxation of rat pulmonary artery by spermine NONOate, a diazeniumdiolate nitric oxide donor
Authors: Homer Kerry L , Wanstall Janet C 
Published: January 2005

In rat pulmonary artery pre‐contracted with phenylephrine, the mechanisms of relaxation to the nitric oxide (NO) donor, spermine NONOate, were investigated.
Responses to spermine NONOate were only partially blocked by the soluble guanylate cyclase inhibitor, ODQ (1H‐[1,2,4]Oxadiazolo‐[4,3,‐a]quinoxalin‐1‐one) at concentrations up to 30 μM. Ten μM ODQ gave maximal inhibition. Endothelium removal had no effect on the potency of spermine NONOate or its inhibition by ODQ.
The protein kinase G inhibitor, Rp‐8‐Br‐cGMPS (100 μM), caused minimal inhibition of spermine NONOate despite causing marked inhibition of glyceryl trinitrate and isosorbide dinitrate.
Spermine NONOate (100 μM) caused a 35 fold increase in guanosine 3′5′ cyclic monophosphate (cyclic GMP) above basal levels in pulmonary artery rings. ODQ (3 μM) abolished this cyclic GMP production but did not inhibit corresponding relaxant responses. Similar results were seen with another NONOate (MAHMA NONOate; 10 μM).
ODQ‐resistant relaxation to spermine NONOate (i.e. relaxation seen in the presence of 10 μM ODQ) was inhibited by potassium (80 mM), charybdotoxin (300 nM), iberiotoxin (300 nM), apamin (100 nM), ouabain (1 mM) or thapsigargin (100 nM) but not by 4‐aminopyridine (3 mM), glybenclamide (10 μM) or diltiazem (10 μM).
Potassium, charybdotoxin, ouabain and thapsigargin also inhibited ODQ‐resistant relaxation to FK409 ((±)‐E‐4‐ethyl‐2‐[E‐hydroxyimino]‐5‐nitro‐3‐hexenamide).
We conclude that, on rat pulmonary artery, spermine NONOate can produce cyclic GMP‐independent relaxation that involves, at least in part, activation of Na+/K+‐ATPase, sarco‐endoplasmic reticulum Ca2+‐ATPase and calcium‐activated potassium channels.

British Journal of Pharmacology (2000) 131, 673–682; doi:10.1038/sj.bjp.0703613
Evidence that PAR‐1 and PAR‐2 mediate prostanoid‐dependent contraction in isolated guinea‐pig gallbladder
Authors: Tognetto Michele , Trevisani Marcello , Maggiore Barbara , Navarra Giuseppe , Turini Alessandro , Guerrini Remo , Bunnett Nigel W , Geppetti Pierangelo , Harrison Selena 
Published: January 2005

We have investigated the ability of protease‐activated receptor‐1 (PAR‐1), PAR‐2, PAR‐3 and PAR‐4 agonists to induce contractile responses in isolated guinea‐pig gallbladder. Thrombin, trypsin, mouse PAR‐1 activating (SFLLRN‐NH2) peptide, and mouse PAR‐2 activating (SLIGRL‐NH2) and human PAR‐2 activating (SLIGKV‐NH2) peptides produced a concentration‐dependent contractile response.
Mouse PAR‐4 activating (GYPGKF‐NH2) peptide, the mouse PAR‐1 reverse (NRLLFS‐NH2) peptide, the mouse PAR‐2 reverse (LRGILS‐NH2) and human PAR‐2 reverse (VKGILS‐NH2) peptides caused negligible contractile responses at the highest concentrations tested.
An additive effect was observed following the contractile response induced by either trypsin or thrombin, with the addition of a different PAR agonist (SFLLRN‐NH2 and SLIGRL‐NH2, respectively). Desensitization to PAR‐2 activating peptide attenuated the response to trypsin but failed to attenuate the response to PAR‐1 agonists, and conversely desensitization to PAR‐1 attenuated the response to thrombin but failed to alter contractile responses to PAR‐2 agonists.
The contractile responses produced by thrombin, trypsin, SFLLRN‐NH2 and SLIGRL‐NH2 were markedly reduced in the presence of the cyclo‐oxygenase inhibitor, indomethacin, whilst the small contractile response produced by NRLLFS‐NH2 and LRGILS‐NH2 were insensitive to indomethacin.
The contractile responses to thrombin, trypsin, SFLLRN‐NH2 and SLIGRL‐NH2 were unaffected by the presence of: the non‐selective muscarinic antagonist, atropine; the nitric oxide synthase inhibitor, L‐NAME; the sodium channel blocker, tetrodotoxin; the combination of selective tachykinin NK1 and NK2 receptor antagonists, (S)‐1‐[2‐[3‐(3,4‐dichlorphenyl)‐1 (3‐isopropoxyphenylacetyl) piperidin‐3‐yl] ethyl]‐4‐phenyl‐1 azaniabicyclo [2.2.2] octane chloride (SR140333) and (S)‐N‐methyl‐N‐[4‐acetylamino‐4‐phenylpiperidino‐2‐(3,4‐dichlorophenyl)‐butyl] benzamide (SR48968), respectively.
The results indicate that PAR‐1 and PAR‐2 activation causes contractile responses in the guinea‐pig gallbladder, an effect that is mediated principally by prostanoid release, and is independent of neural mechanisms.

British Journal of Pharmacology (2000) 131, 689–694; doi:10.1038/sj.bjp.0703618