bluuebunny/crossref_metadata_2025_split huggingface dataset:
α2‐Adrenoceptor and NPY receptor‐mediated contractions of porcine isolated blood vessels: evidence for involvement of the vascular endothelium
Authors: Roberts R E , Kendall D A , Wilson V G 
Published: January 2005

Enhanced contractions to the α2‐adrenoceptor agonist UK14304 and neuropeptide Y (NPY) in the porcine ear artery can be uncovered by pharmacological manipulation. The aim of this study was to determine whether similar pharmacological manipulation can uncover enhanced contractions in the porcine splenic artery, and to determine whether the endothelium modulates these responses.
UK14304 (0.3 μM) and NPY (0.1 μM) produced small contractions of the porcine splenic artery. After pre‐contraction of the tissue with U46619, followed by relaxation with forskolin, the responses to both UK14304 and NPY were enhanced. Enhanced contractions to both UK14304 and NPY were also obtained after relaxation with SNP. These results demonstrate that, as in the porcine ear artery, α2‐adrenoceptors and NPY receptors are able to produce enhanced contractile responses through both adenylyl cyclase‐dependent and ‐independent signal transduction pathways.
Removal of the endothelium had no significant effect on responses to UK14304 either alone or in the presence of U46619 and forskolin in the porcine splenic artery. On the other hand, responses to UK14304 after relaxation with SNP were reduced after endothelium‐denudation in both the porcine splenic artery and ear artery. Similar results were obtained with NPY in the porcine ear artery.
In conclusion, enhanced contractile responses to UK14304 and NPY in the porcine splenic artery can be uncovered using methods similar to those employed in the porcine ear artery. Under certain conditions the responses to both agents are modulated by the endothelium. These data highlight further the similarities in the signal transduction pathways used by both α2‐adrenoceptors and NPY receptors to induce vasoconstriction.

British Journal of Pharmacology (1999) 128, 1705–1712; doi:10.1038/sj.bjp.0702979
Functional group I metabotropic glutamate receptors in submucous plexus of guinea‐pig ileum
Authors: Hu Hong‐Zhen , Ren Jun , Liu Sumei , Gao Chuanyun , Xia Yun , Wood Jackie D 
Published: January 2005

Intracellular recording methods and immunostaining revealed the existence of functional group I metabotropic glutamate receptors (mGluRs) in submucous plexus neurons of guinea‐pig ileum. Selective group I, but not groups II or III metabotropic glutamate receptor agonists induced concentration‐dependent, slowly‐activating depolarizing responses. Group I metabotropic glutamate receptor antagonism observed with (S)‐4‐carboxyphenylglycine (S‐4‐CPG) (100–600 μM) was competitive as determined by Schild analysis (pA2=3.81±0.02). Neither the group II and III metabotropic nor ionotropic glutamate receptor antagonists altered responses evoked by group I receptor agonists. Immunoreactivities for metabotropic glutamate 1α and 5 receptors were found to locate exclusively in neurons in the submucous plexus of guinea‐pig ileum with the highest density around the cell bodies. The results suggest that group I metabotropic glutamate receptors are functionally expressed in the submucous plexus of guinea‐pig small intestine.British Journal of Pharmacology (1999) 128, 1631–1635; doi:10.1038/sj.bjp.0702980
Stimulation of the ventral tegmental area enhances the effect of vasopressin on blood pressure in conscious rats
Authors: Van Den Buuse Maarten , Catanzariti Renaldo 
Published: January 2005

The mesolimbic dopamine system projects to a large number of forebrain areas and plays an important role in the regulation of locomotor activity, cognition and reward. We previously found evidence for a functional interaction between the mesolimbic dopamine system and circulating vasopressin and the present study was performed to test the hypothesis that mesolimbic dopamine stimulation modulates the cardiovascular effects of vasopressin.Sprague‐Dawley rats were stereotaxically implanted with a guide cannula into the region of origin of the mesolimbic system, the ventral tegmental area, and instrumented with catheters into the abdominal aorta and jugular vein. One week later, separate groups of conscious rats were injected intravenously with 1, 3 or 10 ng kg−1of arginine‐vasopressin or other vasopressor drugs before and after intra‐ventral tegmental area injection of 10 nmol of neurotensin.Intra‐ventral tegmental area injections of neurotensin had no significant effect on mean arterial pressure and heart rate but significantly potentiated the pressor response to intravenous administration of vasopressin when compared to saline‐injections. However, the vasopressin‐induced bradycardia was unaffected. Intravenous pretreatment with raclopride blocked the ability of neurotensin, injected into the ventral tegmental area, to potentiate the vasopressin‐induced pressor response. Intra ventral tegmental area injections of neurotensin had no effect on the pressor response and bradycardia induced by intravenous angiotensin II or methoxamine.In conclusion, these results suggest that the mesolimbic dopamine system, in addition to its well‐known role in the regulation of behaviour, modulates cardiovascular control by potentiating the effects of vasopressin on mean arterial pressure.British Journal of Pharmacology(2000)129, 29–36; doi:10.1038/sj.bjp.0702982
[125I]‐GR231118: a high affinity radioligand to investigate neuropeptide Y Y1 and Y4 receptors
Authors: Dumont Yvan , Quirion Rémi 
Published: January 2005

GR231118 (also known as 1229U91 and GW1229), a purported Y1 antagonist and Y4 agonist was radiolabelled using the chloramine T method.
[125I]‐GR231118 binding reached equilibrium within 10 min at room temperature and remained stable for at least 4 h.
Saturation binding experiments showed that [125I]‐GR231118 binds with very high affinity (Kd of 0.09–0.24 nM) in transfected HEK293 cells with the rat Y1 and Y4 receptor cDNA and in rat brain membrane homogenates. No specific binding sites could be detected in HEK293 cells transfected with the rat Y2 or Y5 receptor cDNA demonstrating the absence of significant affinity of GR231118 for these two receptor classes.
Competition binding experiments revealed that specific [125I]‐GR231118 binding in rat brain homogenates is most similar to that observed in HEK293 cells transfected with the rat Y1, but not rat Y4, receptor cDNA.
Autoradiographic studies demonstrated that [125I]‐GR231118 binding sites were fully inhibited by the Y1 antagonist BIBO3304 in most areas of the rat brain. Interestingly, high percentage of [125I]‐GR231118/BIBO3304‐insensitive binding sites were detected in few areas. These [125I]‐GR231118/BIBO3304‐insensitive binding sites likely represent labelling to the Y4 receptor subtype.
In summary, [125I]‐GR231118 is a new radiolabelled probe to investigate the Y1 and Y4 receptors; its major advantage being its high affinity. Using highly selective Y1 antagonists such as BIBO3304 or BIBP3226 it is possible to block the binding of [125I]‐GR231118 to the Y1 receptor allowing for the characterization and visualization of the purported Y4 subtype.

British Journal of Pharmacology (2000) 129, 37–46; doi:10.1038/sj.bjp.0702983
Individual sympathetic varicosities possess different sensitivities to alpha 2 and P2 receptor agonists and antagonists in mouse vas deferens
Authors: O'Connor S C , Brain K L , Bennett M R 
Published: January 2005

The diversity of α2 and purinergic autoreceptor actions on action potential evoked calcium transients in single varicosities has been investigated using the calcium indicator Oregon Green 488 BAPTA‐1.
During long trains of impulses (10 Hz for 30 s), the change in calcium concentration in varicosities from its resting level (Δ[Ca2+]v) increased in many varicosities during the first 3 s of stimulation before reaching a plateau.
The α2 adrenoceptor agonist clonidine (1 μM) decreased Δ[Ca2+]v by over 40% during short trains (five impulses at 5 Hz) in most varicosities, although some were unaffected. The α2 adrenoceptor antagonist idazoxan (2 μM) increased the Δ[Ca2+]v plateau following long trains in most varicosities. Hence, most varicosities possess α2 adrenoceptors which are activated when noradrenaline accumulates extracellularly.
During long trains of impulses, the P2y‐purinergic receptor agonist 2‐methyl‐thio‐ATP (100 μM) decreased Δ[Ca2+]v plateau by about 50% in most varicosities; α,β‐methylene ATP (100 μM) decreased it by about 50% in a minority of varicosities; adenosine (200 μM) had no significant effect. Suramin (100 μM) increased the Δ[Ca2+]v during all stimulus protocols in most varicosities, suggesting that ambient ATP modulates Δ[Ca2+]v responses. The P2y receptor antagonist reactive blue (100 μM) affected a minority of varicosities. Given that most varicosities respond to suramin, other P2 receptor subtypes are probably present.
The ATP ectoenzyme antagonist ARL67157 (50 μM) decreased the plateau Δ[Ca2+]v during long trains in complete strings of varicosities but not in others.
The present technique indicates that varicosities have diverse autoreceptor utilization.

British Journal of Pharmacology (1999) 128, 1739–1753; doi:10.1038/sj.bjp.0702984
Regional haemodynamic responses to infusion of lipopolysaccharide in conscious rats: effects of pre‐ or post‐treatment with glibenclamide
Authors: Gardiner S M , Kemp P A , March J E , Bennett T 
Published: January 2005

To determine the putative contribution of KATP‐channels to the haemodynamic sequelae of endotoxaemia, three experiments were carried out in different groups of conscious, chronically‐instrumented, unrestrained, male Long Evans rats.
In the first experiment, pretreatment with the KATP‐channel antagonist, glibenclamide, abolished the initial hypotension, but not the renal vasodilatation caused by LPS infusion. Subsequently, however, in the presence of glibenclamide and LPS there was a significant increase in mean arterial blood pressure, and a bradycardia, in contrast to the fall in mean arterial blood pressure and the tachycardia seen in the presence of vehicle and LPS. The pressor and bradycardic changes in the presence of glibenclamide and LPS were accompanied by significant reductions in hindquarters flow and vascular conductance, and these were significantly greater than those seen in the presence of vehicle and LPS, or glibenclamide and saline.
Administration of glibenclamide 6 h after the onset of saline and LPS infusion, or 6 h after the onset of saline and LPS infusion in the presence of the AT1‐receptor antagonist, losartan, and the ETA‐, ETB‐ receptor antagonist, SB 209670, in the absence or presence of dexamethasone, caused a significant increase in mean arterial blood pressure and reductions in renal, mesenteric and hindquarters conductances, although the latter was the only vascular bed in which there was a reduction in flow.
The results are consistent with a contribution from KATP‐channels to the vasodilatation caused by LPS, particularly in the hindquarters vascular bed.

British Journal of Pharmacology (1999) 128, 1772–1778; doi:10.1038/sj.bjp.0702985
(−)1‐(Benzofuran‐2‐yl)‐2‐propylaminopentane, [(−)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain
Authors: Knoll Joseph , Yoneda Fumio , Knoll Berta , Ohde Hironori , Miklya Ildikó 
Published: January 2005

The brain constituents β‐phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain (‘catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect’). (−)Deprenyl (Selegiline) and (−)1‐phenyl‐2‐propylaminopentane [(−)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property.
By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (−)1‐(benzofuran‐2‐yl)‐2‐propylaminopentane [(−)BPAP] was selected as a potential follower of (−)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain.
(−)BPAP significantly enhanced in 0.18 μmol 1−1 concentration the impulse propagation mediated release of [3H]‐noradrenaline and [3H]‐dopamine and in 36 nmol 1−1 concentration the release of [3H]‐serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10−12–10−14 M (−)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of β‐amyloid in 10−14 M concentration. In rats (−)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 μg kg−1 s.c. In the shuttle box, (−)BPAP in rats was about 130 times more potent than (−)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

British Journal of Pharmacology (1999) 128, 1723–1732; doi:10.1038/sj.bjp.0702995
P‐glycoprotein‐ and mrp2‐mediated octreotide transport in renal proximal tubule
Authors: Gutmann Heike , Miller David S , Droulle Agathe , Drewe Jürgen , Fahr Alfred , Fricker Gert 
Published: January 2005

Transepithelial transport of a fluorescent derivative of octreotide (NBD‐octreotide) was studied in freshly isolated, functionally intact renal proximal tubules from killifish (Fundulus heteroclitus).
Drug accumulation in the tubular lumen was visualized by means of confocal microscopy and was measured by image analysis. Secretion of NBD‐octreotide into the tubular lumen was demonstrated and exhibited the all characteristics of specific and energy‐dependent transport. Steady state luminal fluorescence averaged about five times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN.
NBD‐octreotide secretion was inhibited in a concentration‐dependent manner by unlabelled octreotide, verapamil and leukotriene C4 (LTC4). Conversely, unlabelled octreotide reduced in a concentration dependent manner the p‐glycoprotein (Pgp)‐mediated secretion of a fluorescent cyclosporin A derivative (NBDL‐CS) and the mrp2‐mediated secretion of fluorescein methotrexate (FL‐MTX).
This inhibition was not due to impaired metabolism or toxicity since octreotide had no influence on the active transport of fluorescein (FL), a substrate for the classical renal organic anion transport system.
The data are consistent with octreotide being transported across the brush border membrane of proximal kidney tubules by both Pgp and mrp2.

British Journal of Pharmacology (2000) 129, 251–256; doi:10.1038/sj.bjp.0703003
Effects of nicotine and chlorisondamine on cerebral glucose utilization in immobilized and freely‐moving rats
Authors: Marenco T , Bernstein S , Cumming P , Clarke P B S 
Published: January 2005

Chlorisondamine blocks central nicotinic receptors for many weeks via an unknown mechanism. Intracerebroventricular administration of [3H]‐chlorisondamine in rats results in an anatomically restricted and persistent intracellular accumulation of radioactivity. The initial aim of the present study was to test whether nicotinic receptor antagonism by chlorisondamine is also anatomically restricted.
Male adult rats were pretreated several times with nicotine to avoid the disruptive effects of the drug seen in drug‐naïve animals. They then received chlorisondamine (10 μg i.c.v.) or saline, and local cerebral glucose utilization (LCGU) was measured 4 weeks later after acute nicotine (0.4 mg kg−1 s.c.) or saline administration. During testing, rats were partially immobilized. Nicotine significantly increased LCGU in the anteroventral thalamus and in superior colliculus. Chlorisondamine completely blocked the first of these effects. Chlorisondamine significantly reduced LCGU in the lateral habenula, substantia nigra pars compacta, ventral tegmental area, and cerebellar granular layer.
The second experiment was of similar design, but the rats were not pre‐exposed to nicotine, and were tested whilst freely‐moving. Acute nicotine significantly increased LCGU in anteroventral thalamus, superior colliculus, medial habenula and dorsal lateral geniculate. Overall, however, nicotine significantly decreased LCGU. Most or all of the central effects of nicotine on LCGU were reversed by chlorisondamine given 4 weeks beforehand.
These findings suggest that chlorisondamine blocks nicotinic effects widely within the brain. They also indicate that in freely‐moving rats, nicotine can reduce or stimulate cerebral glucose utilization, depending on the brain area.

British Journal of Pharmacology (2000) 129, 147–155; doi:10.1038/sj.bjp.0703005
Contraction to big endothelin‐1, big endothelin‐2 and big endothelin‐3, and endothelin‐converting enzyme inhibition in human isolated bronchi
Authors: Yap E Y S , Battistini B , McKay K O 
Published: January 2005

All three endothelin precursor peptides, i.e. big endothelin‐1 (big ET‐1), big endothelin‐2 (big ET‐2) and big endothelin‐3 (big ET‐3), produced contractile responses in human isolated bronchi, demonstrating the presence of functional endothelin‐converting enzyme (ECE) in this tissue.
The maximal contractile responses were equal to 108.4±8.0% (0.1 μM big ET‐1; n=4), 85.2±11.8% (0.1 μM big ET‐2; n=7) and 43.0±7.2% (0.1 μM big ET‐3; n=5) of the reference response to acetylcholine (1 mM).
The response to big ET‐1 (0.1 μM), but not endothelin‐1 (ET‐1, 0.1 μM), was diminished after overnight storage of the tissue at 4°C, demonstrating instability of the enzyme.
The responses to all three big‐endothelins were significantly inhibited, by the ECE inhibitors CGS 26393 and CGS 26303, in a concentration‐related manner.
The responses to the mature peptides ET‐1, endothelin‐2 (ET‐2), and endothelin‐3 (ET‐3) were unaffected by CGS 26393 and CGS 26303.
Phosphoramidon (10 μM) also produced an inhibition of the response to big ET‐1 that was equivalent to that produced by CGS 26393 (10 μM). Combination of CGS 26393 (10 μM) and phosphoramidon (10 μM) did not produce an additive inhibition.
These results demonstrate the presence of functional ECE for all three big endothelins in human bronchus and inhibition of the enzyme by newly developed orally active ECE inhibitors, as well as phosphoramidon.

British Journal of Pharmacology (2000) 129, 170–176; doi:10.1038/sj.bjp.0703006
Role of gap junctions in the responses to EDHF in rat and guinea‐pig small arteries
Authors: Edwards G , Félétou M , Gardener M J , Thollon C , Vanhoutte P M , Weston A H 
Published: January 2005

In guinea‐pig internal carotid arteries with an intact endothelium, acetylcholine (10 μM) and levcromakalim (10 μM) each hyperpolarized the smooth muscle whereas a 5 mM elevation of extracellular K+ was without effect.
Incubation of the carotid artery with the gap junction inhibitors carbenoxolone (100 μM) or gap 27 (500 μM) essentially abolished the hyperpolarization to acetylcholine but it was without effect on that to levcromakalim. Carbenoxolone had no effect on the acetylcholine‐induced endothelial cell hyperpolarization but inhibited the smooth muscle hyperpolarization induced by the endothelial cell K+ channel opener, 1‐ethyl‐2‐benzimidazolinone (600 μM).
In rat hepatic and mesenteric arteries with endothelium, carbenoxolone (100 or 500 μM) depolarized the smooth muscle but did not modify hyperpolarizations induced by KCl or levcromakalim. In the mesenteric (but not the hepatic) artery, the acetylcholine‐induced hyperpolarization was inhibited by carbenoxolone.
Phenylephrine (1 μM) depolarized the smooth muscle cells of intact hepatic and mesenteric arteries, an effect enhanced by carbenoxolone. Gap 27 did not have a depolarizing action. In the presence of phenylephrine, acetylcholine‐induced hyperpolarization of both hepatic and mesenteric artery myocytes was partially inhibited by each of the gap junction inhibitors.
Collectively, the data suggest that gap junctions play some role in the EDHF (endothelium‐derived hyperpolarizing factor) response in rat hepatic and mesenteric arteries. However, in the guinea‐pig internal carotid artery, electrotonic propagation of endothelial cell hyperpolarizations via gap junctions may be the sole mechanism underlying the response previously attributed to EDHF.

British Journal of Pharmacology (1999) 128, 1788–1794; doi:10.1038/sj.bjp.0703009
The peripheral antinociceptive effect induced by morphine is associated with ATP‐sensitive K+ channels
Authors: Rodrigues A R A , Duarte I D G 
Published: January 2005

The effect of several K+ channel blockers such as glibenclamide, tolbutamide, charybdotoxin (ChTX), apamin, tetraethylammonium (TEA), 4‐aminopyridine (4‐AP) and cesium on the peripheral antinociceptive effect of morphine was evaluated by the paw pressure test in Wistar rats.
The intraplantar administration of a carrageenan suspension (250 μg) resulted in an acute inflammatory response and a decreased threshold to noxious pressure. Morphine administered locally into the paw (25, 50, 100 and 200 μg) elicited a dose‐dependent antinociceptive effect which was demonstrated to be mediated by a peripheral site up to the 100 μg dose.
The selective blockers of ATP‐sensitive K+ channels glibenclamide (20, 40 and 80 μg paw−1) and tolbutamide (40, 80 and 160 μg paw−1) antagonized the peripheral antinociception induced by morphine (100 μg paw−1).
This effect was unaffected by ChTX (0.5, 1.0 and 2.0 μg paw−1), a large conductance Ca2+‐activated K+ channel blocker, or by apamin (2.5, 5.0 and 10.0 μg paw−1), a selective blocker of a small conductance Ca2+‐activated K+ channel.
Intraplantar administration of the non‐specific K+ channel blockers TEA (160, 320 and 640 μg), 4‐AP (10, 50 and 100 μg) and cesium (125, 250 and 500 μg) also did not modify the peripheral antinociceptive effect of morphine.
These results suggest that the peripheral antinociceptive effect of morphine may result from activation of ATP‐sensitive K+ channels, which may cause a hyperpolarization of peripheral terminals of primary afferents, leading to a decrease in action potential generation. In contrast, large conductance Ca2+‐activated K+ channels, small conductance Ca2+‐activated K+ channels as well as voltage‐dependent K+ channels appear not to be involved in this transduction pathway.

British Journal of Pharmacology (2000) 129, 110–114; doi:10.1038/sj.bjp.0703038