bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that mast cell degranulation, histamine and tumour necrosis factor α release occur in LPS‐induced plasma leakage in rat skin
Authors: Iuvone Teresa , Van Den Bossche Rita , D'Acquisto Fulvio , Carnuccio Rosa , Herman Arnold G 
Published: January 2005

In the present study we investigated the role of mast cells during inflammation in rat skin. As the release of several pro‐inflammatory mediators, such as histamine and tumour necrosis factor α (TNFα), occurs following mast cell activation we studied whether mast cell degranulation and the release of both histamine (H) and TNFα occurred in a model of lipopolysaccharide (LPS)‐induced plasma leakage in rat skin.
Plasma leakage in the rat skin was measured over a period of 2 h as the local accumulation of intravenous injection of 125I‐human serum albumin (125I‐HSA) in response to intradermal injection of LPS. LPS (10 μg site−1) produced an increase of plasma leakage (50.1±2.3 μl site−1) as compared to saline (9.0±3.2 μl site−1). Histological analysis of rat tissue showed that LPS induced a remarkable mast cell degranulation (59.8±2.1%) as compared to saline (13.5±2.2%).
Ketotifen (10−9–10−7 mol site−1), a well‐known mast cell‐membrane stabilizer, produced a dose‐related inhibition of LPS‐induced plasma leakage by 36±3.5%, 47±4.0%, 60±3.3% respectively. In addition, ketotifen (10−7 mol site−1) inhibited mast cell degranulation by 59.2±2.7%.
Chlorpheniramine maleate (CPM) (10−9–10−7 mol site−1), an H1 histamine receptor antagonist only partially inhibited LPS‐induced plasma leakage in rat skin (38±1.1% at the highest dose). Furthermore, CPM (10−7 mol site−1) did not prevent mast cell degranulation.
A polyclonal antibody against TNFα (1 : 500, 1 : 100, 1 : 50 v  v−1 dilution), locally injected, decreased LPS‐induced plasma leakage in the skin by 15±2.0%, 24±2.1% and 50±3.0% respectively.
Taken together these results suggest that LPS‐induced plasma leakage in rat skin is mediated, at least in part, by mast cell degranulation and by the release of histamine and TNFα from these cells.

British Journal of Pharmacology (1999) 128, 700–704; doi:10.1038/sj.bjp.0702828
Effects of a range of β2 adrenoceptor agonists on changes in intracellular cyclic AMP and on cyclic AMP driven gene expression in cultured human airway smooth muscle cells
Authors: Scott Mark G H , Swan Caroline , Jobson Timothy M , Rees Steve , Hall Ian P 
Published: January 2005

The effects of the selective β2 adrenoceptor agonists salbutamol, terbutaline and salmeterol and the non‐selective β adrenoceptor agonist isoprenaline on [3H]‐cyclic AMP formation and cyclic AMP response element (CRE) driven luciferase expression, assessed using the construct p6CRE/luc, were studied in primary cultures of human airway smooth muscle (HASM) cells.
Optimal transfection conditions for transient expression of pGL3 Control were 4 μg DNA/well71 in a 6 well plate and 1.8 μl Transfectam/μg DNA. Expression was maximal at 48–72 h.
Salbutamol (maximum response 19%, EC50 0.6 μM), terbutaline (maximum response 38%, EC50 2.3 μM) and salmeterol (maximum response 18%, EC50 0.0012 μM) were all partial agonists for cyclic AMP formation compared with isoprenaline (EC50 0.08 μM). However, all of the β2 adrenoceptor agonists produced increases in CRE‐driven luciferase activity, in cultured HASM transfected with the vector p6CRE/luc, which were equivalent or greater (salmeterol) than those seen with isoprenaline.
Both salbutamol and salmeterol were more potent at increasing luciferase expression than in elevating cyclic AMP levels in these cells. The potency ratios (EC50 (cyclic AMP)/EC50 (LUC)) for the agents studied were isoprenaline: 0.2 fold, terbutaline: 3 fold, salbutamol: 24 fold, salmeterol: 38 fold.
These data suggest that important quantitative differences exist in the ability of β2 adrenoceptor agonists to increase whole cell cyclic AMP levels in airway smooth muscle and to drive gene expression via a CRE‐driven mechanism.

British Journal of Pharmacology (1999) 128, 721–729; doi:10.1038/sj.bjp.0702829
YC‐1 potentiates nitric oxide‐induced relaxation in guinea‐pig trachea
Authors: Hwang Tsong‐Long , Wu Chin‐Chung , Teng Che‐Ming 
Published: January 2005

The effects of YC‐1 (3‐(5′‐hydroxymethyl‐2′‐furyl)‐1‐benzylindazole) on tension, levels of cyclic GMP and cyclic AMP were investigated in guinea‐pig trachea. We especially studied the combined effect of YC‐1 with exogenous or endogenous nitric oxide on these parameters.
YC‐1 at the concentration 3 or 10 μM, which caused only minor effect by itself, elicited concentration‐dependent potentiation of sodium nitroprusside (SNP)‐induced tracheal relaxation. This relaxation of YC‐1 with SNP was reversed by ODQ.
Relaxant responses to electric field stimulation (EFS) in the presence of indomethacin, atropine, guanethidine, α‐chymotrypsin and histamine were also markedly increased by YC‐1 (10 μM). In the presence of L‐NAME or ODQ, the relaxant effects to EFS were attenuated and the following addition of YC‐1 did not further enhance relaxation.
YC‐1 (10 μM) or SNP (0.3 μM) alone did not induce significant elevation of cyclic GMP levels in the presence of IBMX, whereas simultaneous application of both compounds markedly elevated the cyclic GMP accumulation. In contrast, the cyclic AMP levels were not altered even at the combination of YC‐1 and SNP. Additionally, YC‐1 also affected cyclic GMP metabolism, since it inhibited the activity of phosphodiesterase type V in human platelets.
YC‐1 (30 μM) did not scavenge superoxide anion and had no effect on the removal of superoxide anion by superoxide dismutase in a xanthine/xanthine oxidase system.
In conclusion, these results indicate that although YC‐1 elicits negligible relaxation of guinea‐pig trachea by itself, it can potentiate the relaxant responses of exogenous or endogenous NO. This synergistic response of YC‐1 is via the elevation of cyclic GMP contents.

British Journal of Pharmacology (1999) 128, 577–584; doi:10.1038/sj.bjp.0702830
Proteinase activated receptor 2: role of extracellular loop 2 for ligand‐mediated activation
Authors: Al‐Ani Bahjat , Saifeddine Mahmoud , Kawabata Atsufumi , Hollenberg Morley D 
Published: January 2005

Rat proteinase‐activated receptor‐2 (PAR2) variants were stably expressed in rat KNRK cells: (a) wild‐type (wt)–PAR2; (b) PAR2PRR, with the extracellular loop 2 (EL‐2) sequence P231E232E233mutated to PRR and (c) PAR2NET, with the EL‐2 sequence, PEEV changed to NETL. Cell lines were evaluated for their sensitivity (calcium signalling) towards trypsin and the receptor‐activating peptides, SLIGRL‐NH2, SLIGEL‐NH2, trans‐cinnamoyl(tc)‐LIGRLO‐NH2, and SFLLR‐NH2.
SLIGEL‐NH2 exhibited low potency (1 : 200 relative to SLIGRL‐NH2) in wild‐type PAR2. Its activity was increased 5 fold in PAR2PRR, but it was inactive in PAR2NET.
In PAR2PRR, the potencies of SLIGRL‐NH2, tc‐LIGRLO‐NH2, and SFLLR‐NH2 were decreased by 80–100 fold. But, the potency of trypsin was decreased by only 7 fold.
In PAR2NET, highly homologous in EL‐2 with proteinase‐activated receptor‐1 (PAR1), the potency of the PAR1‐derived peptide, SFLLR‐NH2, was reduced by 100 fold compared with wt‐PAR2, whereas the potency of the PAR2‐derived AP, SLIGRL‐NH2 was reduced 10 fold. In contrast, the potency of trypsin in PAR2NET was almost the same as in wt‐PAR2.
We conclude that the acidic EL‐2 tripeptide, PEE, in PAR2 plays an important role in governing agonist activity.
The data obtained with the PEEV→NETL mutation suggested: (a) that SLIGRL‐NH2 and SFLLR‐NH2 interact in a distinct manner with PAR2 and (b) that SFLLR‐NH2 may interact differently with PAR2 than it does with PAR1.
The differential reductions in the potencies of SLIGRL‐NH2, compared with trypsin in the PAR2PRR and PAR2NET cell lines point to differences between the interactions of the trypsin‐revealed tethered ligand and the free receptor‐activating peptide with PAR2.

British Journal of Pharmacology (1999) 128, 1105–1113; doi:10.1038/sj.bjp.0702834
Reactive oxygen species generation and histamine release by activated mast cells: modulation by nitric oxide synthase inhibition
Authors: Brooks A C , Whelan C J , Purcell W M 
Published: January 2005

We have examined the generation of intracellular reactive oxygen species (ROS) and release of histamine by rat peritoneal mast cells (RPMC) in response to stimulation with antigen (ovalbumin), compound 48/80, nerve growth factor (NGF) and substance P (SP).
We have also examined the effects of the non‐specific nitric oxide synthase inhibitor, L‐NAME (100 μM) upon the release of histamine and generation of intracellular ROS in response to the named secretagogues.
Ovalbumin (100–1000 μg ml−1), compound 48/80 (0.1–100 μg ml−1), NGF (0.1–100 μg ml−1), and SP (5–50 μM), caused a concentration‐dependent release of histamine from RPMC.
Ovalbumin (1 ng ml−1–0.1 μg ml−1), compound 48/80 (1–100 μg ml−1), NGF (1 pg ml−1–1 μg ml−1), and SP (0.005–50 μM) caused a concentration‐dependent generation of intracellular ROS by RPMC.
Pre‐incubation of RPMC with L‐NAME (100 μM) caused a significant enhancement of both histamine release and intracellular ROS from RPMC in response to ovalbumin, compound 48/80, NGF and SP.
Our data demonstrate that NGF, SP and ovalbumin are capable of causing intracellular ROS generation by RPMC at lower concentrations than those causing significant histamine release and we speculate that this may contribute to the activation of cytokine production.
The data also show that NO modulates histamine release, and ROS generation in response to the secretagogues used. This may have significance in pathologies where NO synthesis is decreased, leading to an increased activation of mast cells.

British Journal of Pharmacology (1999) 128, 585–590; doi:10.1038/sj.bjp.0702838
Tracheal relaxing effects and β2 adrenoceptor selectivity of S1319, a novel sponge‐derived bronchodilator agent, in isolated guinea‐pig tissues
Authors: Suzuki Hidefumi , Ueno Akihiro , Takei Masao , Sindo Kazutoshi , Miura Toru , Sakakibara Masayuki , Higa Tatsuo , Fukamachi Hiromi 
Published: January 2005

S1319 (4‐hydroxy‐7‐[1‐(1‐hydroxy‐2‐methylamino)ethyl]‐1,3‐benzothiazol‐2(3H)‐one acetate), a novel non‐catecholamine β‐adrenoceptor agonist, has been compared with isoprenaline, salbutamol and formoterol for activity in vitro on a range of β‐adrenoceptor containing preparations from guinea‐pig.
S1319, like isoprenaline, salbutamol and formoterol, relaxed preparations of guinea‐pig trachea (contracted by histamine) in a concentration‐dependent manner. The relaxing activity of S1319 appeared to be more potent than that of isoprenaline and salbutamol, and similar to that of formoterol (pD2 values of 10.58±0.03 vs 7.60±0.01, 7.50±0.01 and 10.52±0.04, respectively), and was blocked by the β2‐adrenoceptor selective antagonist (ICI 118,551). The intrinsic activity of S1319 was close to 1.0.
In the β1‐adrenoceptor containing preparations, guinea‐pig right and left atria, a monophasic inotropic response of S1319 was observed. The pD2 value of S1319 for left atrial and right atrial inotropism was 6.70±0.15 and 7.81±0.01, respectively.
The selectivity ratio (trachea/left atrial inotropism) of S1319, formoterol, salbutamol and isoprenaline was 8523, 284, 4.8 and 0.45, respectively. The relative selectivity ratio of S1319 was 18743, 1858 and 30 times greater than that of isoprenaline, salbutamol and formoterol, respectively.
Relaxant responses of guinea‐pig trachea to S1319 declined rapidly when the agonist was washed from the tissues, with complete recovery within 30 min. The duration of action of S1319 was similar to that of isoprenaline and less than that of salbutamol and formoterol.
In summary, S1319, a sponge‐derived β‐adrenoceptor agonist, is a potent and selective β2‐adrenoceptor agonist with a short‐duration of action in isolated guinea‐pig tracheas.

British Journal of Pharmacology (1999) 128, 716–720; doi:10.1038/sj.bjp.0702839
Inhibition of NOS‐2 expression in macrophages through the inactivation of NF‐κB by andalusol
Authors: De Las Heras Beatriz , Navarro Antonio , Díaz‐Guerra María José , Bermejo Paloma , Castrillo Antonio , Boscá Lisardo , Villar Angel 
Published: January 2005

Andalusol, ent‐6α,8α,18‐trihydroxy‐13(16),14‐labdadiene, is a naturally occurring diterpene, isolated from Sideritis foetens (Lamiaceae). This compound exhibited therapeutic activity when evaluated in in vivo models of paw and ear inflammation (Navarro et al., 1997: Z. Naturforsch., 52, 844‐849). The pharmacological effects of this diterpene have been analysed on the activation of the macrophage cell line J774 with lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ).
Incubation of J774 macrophages with andalusol (0.1–100 μM) inhibited the synthesis of nitrite caused by LPS (1 μg ml−1) in concentration and time‐dependent manners. The maximal inhibition was observed when andalusol was added 30 min before LPS stimulation and decreased progressively as the interval between andalusol and LPS challenge increased up to 14 h.
Incubation of J774 cells with LPS resulted in the expression of NOS‐2 protein (130 kDa) as identified by Western blot analysis. The levels of this enzyme decreased significantly in the presence of andalusol (IC50=10.5 μM), suggesting that this diterpene inhibited NOS‐2 expression.
Andalusol inhibited nuclear factor κB activation, a transcription factor necessary for NOS‐2 expression in response to LPS and IFN‐γ. This compound also inhibited the degradation of IκBα favouring the retention of the inactive NF‐κB complexes in the cytosol.
Related compounds to andalusol but lacking the polyol groups were less effective inhibiting NOS‐2 expression in LPS‐activated macrophages. The present findings provide a mechanism by which the anti‐inflammatory properties of this diterpene could be mediated.

British Journal of Pharmacology (1999) 128, 605–612; doi:10.1038/sj.bjp.0702844
Cyclic GMP‐associated apamin‐sensitive nitrergic slow inhibitory junction potential in the hamster ileum
Authors: Matsuyama Hayato , Thapaliya Sharada , Takewaki Tadashi 
Published: January 2005

The mediators of non‐adrenergic, non‐cholinergic (NANC) inhibitory junction potentials (i.j.ps) in the circular smooth muscle cells of the hamster ileum were studied.
Electrical field stimulation (EFS; 0.5 ms duration, 15 V) of the intramural nerves with a train of five pulses at 20 Hz evoked a rapidly developing hyperpolarization (fast i.j.p.) followed by a sustained hyperpolarization (slow i.j.p.).
NG‐nitro‐L‐arginine methyl ester (L‐NAME; 50–200 μM) and NG‐nitro‐L‐arginine (L‐NNA; 50–200 μM), NO synthase inhibitors, inhibited or abolished the EFS‐induced fast and slow NANC i.j.ps. The effects of these NO synthase inhibitors were reversed by L‐arginine (5 mM) but not by D‐arginine (5 mM).
Exogenously applied nitric oxide (NO; 1–100 μM) induced concentration‐dependent hyperpolarizations.
Oxyhaemoglobin (5–50 μM), NO scavenger, inhibited only the slow i.j.p., and the NO‐induced hyperpolarization.
1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxaline‐1‐one (ODQ; 10 μM) and cystamine (10 mM), guanylate cyclase inhibitors, inhibited only the slow i.j.p. Zaprinast (100 μM), a phosphodiesterase type V inhibitor, enhanced the amplitude and duration of the slow i.j.p.
Apamin (100 nM), a small conductance Ca2+‐activated K+ channel blocker, inhibited only the slow i.j.p., and NO‐induced hyperpolarization. A high concentration of 8‐bromoguanosine 3′:5′‐cyclic monophosphate (8‐bromo‐cGMP; 1 mM)‐induced membrane hyperpolarization which was blocked by apamin.
These results suggest that NO, or a related compound, may be the inhibitory transmitter underlying the apamin‐sensitive NANC slow i.j.p. and cyclic GMP mediates the slow i.j.p. in the hamster ileum. It is also likely that NO, without involvement of guanylate cyclase is associated with the fast i.j.p.

British Journal of Pharmacology (1999) 128, 830–836; doi:10.1038/sj.bjp.0702851
Molecular and pharmacological characterization of a functional tachykinin NK3 receptor cloned from the rabbit iris sphincter muscle
Authors: Medhurst Andrew D , Hirst Warren D , Jerman Jeffery C , Meakin Jacqueline , Roberts Jennifer C , Testa Tania , Smart Darren 
Published: January 2005

A functional tachykinin NK3 receptor was cloned from the rabbit iris sphincter muscle and its distribution investigated in ocular tissues.
Standard polymerase chain reaction (PCR) techniques were used to clone a full length rabbit NK3 receptor cDNA consisting of 1404 nucleotides. This cDNA encoded a protein of 467 amino acids with 91 and 87% homology to the human and rat NK3 receptors respectively.
In CHO‐K1 cells transiently expressing the recombinant rabbit NK3 receptor, the relative order of potency of NKB>>NKASP to displace [125I]‐[MePhe7]‐NKB binding and to increase intracellular calcium, together with the high affinity of NK3 selective agonists (e.g. senktide, [MePhe7]‐NKB) and antagonists (e.g. SR 142801, SB 223412) in both assays was consistent with NK3 receptor pharmacology. In binding and functional experiments, agonist concentration response curves were shallow (0.7–0.8), suggesting the possibility of multiple affinity states of the receptor.
Quantitative real time PCR analysis revealed highest expression of rabbit NK3 receptor mRNA in iris sphincter muscle, lower expression in retina and iris dilator muscle, and no expression in lens and cornea. In situ hybridization histochemistry revealed discrete specific localization of NK3 receptor mRNA in the iris muscle and associated ciliary processes. Discrete specific labelling of NK3 receptors with the selective NK3 receptor agonist [125I]‐[MePhe7]‐NKB was also observed in the ciliary processes using autoradiography.
Our study reveals a high molecular similarity between rabbit and human NK3 receptor mRNAs, as predicted from previous pharmacological studies, and provide the first evidence that NK3 receptors are precisely located on ciliary processes in the rabbit eye. In addition, there could be two affinity states of the receptor which may correspond to the typical and ‘atypical’ NK3 receptor subtypes previously reported.

British Journal of Pharmacology (1999) 128, 627–636; doi:10.1038/sj.bjp.0702854
Enhanced phenylephrine‐induced rhythmic activity in the atherosclerotic mouse aorta via an increase in opening of KCa channels: relation to Kv channels and nitric oxide
Authors: Jiang Jiahua , Thorén Peter , Caligiuri Giuseppina , Hansson Göran K , Pernow John 
Published: January 2005

Mice lacking the apolipoprotein E and low density lipoprotein receptor genes (E°×LDLR°) develop atherosclerosis. The aim of this study was to investigate changes in endothelium‐dependent vasodilation and vasomotion in thoracic aortic rings of E°×LDLR° mice.
K+‐induced contractions of the aorta from E°×LDLR° mice were stronger than those from control mice. The sensitivity of E°×LDLR° aorta to phenylephrine (PE) was decreased but the maximal contractions were increased. Acetylcholine‐induced, but not sodium nitroprusside‐induced, relaxations of E°×LDLR° aorta was decreased.
PE induced rhythmic activity in both E°×LDLR° and control aorta but the amplitude was larger in E°×LDLR° than in control mice. PE‐induced rhythmic activity in both E°×LDLR° and control aorta was augmented by increase in extracellular Ca2+‐concentration, but was abolished by removal of the endothelium, the nitric oxide (NO) synthase inhibitor N‐nitro‐L‐arginine methyl ester, the guanylate cyclase inhibitor LY‐83583, high K+ solution and ryanodine.
4‐Aminopyridine, a voltage‐dependent potassium (KV) channel blocker, increased basal tension and induced rhythmic activity in E°×LDLR° aorta but not in control aorta.
The Ca2+‐activated potassium (KCa) channel blockers tetraethylammonium and charybdotoxin abolished PE‐induced rhythmic activity in E°×LDLR° aorta.
In conclusion, opening of Kv channels in E°×LDLR° mice aorta is reduced and it is susceptible to be depolarized resulting in Ca2+ entry. The vascular smooth muscle is then dependent on compensatory mechanisms to limit Ca2+‐entry. Such mechanisms may be decreased sensitivity to vasoconstrictors, or increased opening of KCa channels by NO via a cyclic GMP‐dependent mechanism.

British Journal of Pharmacology (1999) 128, 637–646; doi:10.1038/sj.bjp.0702855
Modulation of sibutramine‐induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2‐adrenoceptors
Authors: Wortley K E , Heal D J , Stanford S C 
Published: January 2005

The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely‐moving rats were investigated using microdialysis. The role of presynaptic α2‐adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.
Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.
In both the cortex and hypothalamus, pretreatment of rats with the α2‐adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.
Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.
These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2‐adrenoceptors. Furthermore, the data suggest that terminal α2‐adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex.

British Journal of Pharmacology (1999) 128, 659–666; doi:10.1038/sj.bjp.0702859
Evidence that histamine homologues discriminate between H3‐receptors in guinea‐pig cerebral cortex and ileum longitudinal muscle myenteric plexus
Authors: Harper E A , Shankley N P , Black J W 
Published: January 2005

The binding of the selective histamine H3‐receptor agonist ([3H]‐R‐α‐methylhistamine) to sites in guinea‐pig cerebral cortex and ileum longitudinal muscle myenteric plexus has been characterized and a comparison made of the apparent affinities of a series of H3‐receptor ligands.
Saturation analysis suggested that [3H]‐R‐α‐methylhistamine labelled a homogeneous population of histamine H3‐receptors in guinea‐pig cerebral cortex (pKD=9.91±0.07; nH=1.07±0.03; n=5) and ileum longitudinal muscle myenteric plexus (pKD=9.75±0.21; nH=0.97±0.02; n=5). There was no significant difference in the estimated affinity of [3H]‐R‐α‐methylhistamine in the two tissues. The cerebral cortex had a significantly higher receptor density (3.91±0.37 fmol mg−1 tissue) than the ileum longitudinal muscle myenteric plexus (0.39±0.11 fmol mg−1).
Overall, the apparent affinities of compounds, classified as H3‐receptor ligands, in cerebral cortex and ileum longitudinal muscle myenteric plexus were well correlated (r=0.91, P<0.0001) and consistent with the cerebral cortex and ileum longitudinal muscle myenteric plexus expressing histamine H3‐receptor population(s) that are pharmacologically indistinguishable by the majority of histamine H3‐receptor ligands. However, it was evident that the homologues of histamine within this group of compounds could discriminate between the receptor populations in the two tissues. Thus, the estimated affinity of five imidazole unbranched alkylamines (histamine, homohistamine, VUF4701, VUF4732 and impentamine) were significantly higher in the guinea‐pig cerebral cortex than in the ileum longitudinal muscle myenteric plexus assay.

British Journal of Pharmacology (1999) 128, 751–759; doi:10.1038/sj.bjp.0702861