bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation by glucocorticoids of responses to eosinopoietic cytokines in bone‐marrow from normal and allergic mice
Authors: Gaspar Elsas Maria Ignez C , Maximiano Elisabeth S , Joseph Danielle , Alves Letícia , Topilko Andrzej , Vargaftig B Boris , Xavier Elsas P 
Published: January 2005

Since the production of eosinopoietic cytokines (GM‐CSF, IL‐3, IL‐5) is inhibited by glucocorticoids, while responsiveness to these cytokines is enhanced in bone‐marrow of allergic mice, we studied the ability of glucocorticoids to modulate murine bone‐marrow eosinopoiesis.
Progenitor (semi‐solid) and/or precursor (liquid) cultures were established from bone‐marrow of: (a) normal mice; (b) ovalbumin‐sensitized and challenged mice or (c) dexamethasone (1–5 mg kg−1) injected mice. Cultures were established with GM‐CSF (2 ng ml−1) or IL‐5 (1 ng ml−1), respectively, alone or associated with dexamethasone, hydrocortisone or corticosterone. Total myeloid colony numbers, frequency and size of eosinophil colonies, and numbers of eosinophil‐peroxidase‐positive cells were determined at day 7.
In BALB/c mice, dexamethasone (10−7 M) increased GM‐CSF‐stimulated myeloid colony formation (P=0.01), as well as the frequency (P=0.01) and size (P<0.01) of eosinophil colonies. Dexamethasone (10−7 M) alone had no effect. Dexamethasone (10−7–10−10 M) increased (P<0.002) eosinophil precursor responses to IL‐5. Potentiation by dexamethasone was still detectable: (a) on low density, immature, nonadherent BALB/c bone‐marrow cells, (b) on bone‐marrow from other strains, and (c) on cells from allergic mice. Hydrocortisone and corticosterone had similar effects. Dexamethasone administered in vivo, 24 h before bone‐marrow harvest, increased subsequent progenitor responses to GM‐CSF (P=0.001) and precursor responses to IL‐5 (P<0.001). These effects were blocked by RU 486 (20 mg kg−1, orally, 2 h before dexamethasone, or added in vitro at 10 μM, P<0.001).
Glucocorticoids, acting in vivo or in vitro, through glucocorticoid receptors, enhance bone‐marrow eosinopoiesis in naïve and allergic mice.

British Journal of Pharmacology (2000) 129, 1543–1552; doi:10.1038/sj.bjp.0703145
Active transport of the angiotensin‐II antagonist losartan and its main metabolite EXP 3174 across MDCK‐MDR1 and Caco‐2 cell monolayers
Authors: Soldner Andrea , Benet Leslie Z , Mutschler Ernst , Christians Uwe 
Published: January 2005

We studied the functional interaction between transport and metabolism by comparing the transport of losartan and its active metabolite EXP 3174 (EXP) across cell monolayers.
Epithelial layers of Caco‐2 cells as well as MDR1, MRP‐1 and MRP‐2 overexpressing cells, in comparison to the respective wildtypes, were used to characterize the transcellular transport of losartan and EXP.
Losartan transport in MDCK‐MDR1 and Caco‐2 cells was saturable and energy‐dependent with a significantly greater basolateral‐to‐apical (B/A) than apical‐to‐basolateral (A/B) flux (ratio=31±1 in MDCK‐MDR1 and ratio 4±1 in Caco‐2 cells). The B/A flux of losartan was inhibited by cyclosporine and vinblastine, inhibitors of P‐glycoprotein and MRP. In contrast, no active losartan transport was observed in MRP‐1 or MRP‐2 overexpressing cells.
The metabolite was only transported in Caco‐2 cells with a B/A‐to‐A/B ratio of 5±1, while lacking active transport in the MDR1, MRP‐1 or MRP‐2 overexpressing cells. The B/A flux of EXP was significantly inhibited by cyclosporine and vinblastine.
In conclusion, losartan is transported by P‐glycoprotein and other intestinal transporters, that do not include MRP‐1 and MRP‐2. In contrast, the carboxylic acid metabolite is not a P‐glycoprotein substrate, but displays considerably higher affinity for other transporters than losartan, that again most probably do not include MRP‐1 and MRP‐2.

British Journal of Pharmacology (2000) 129, 1235–1243; doi:10.1038/sj.bjp.0703150
Factors influencing the low‐frequency associated nicotinic ACh autoreceptor‐mediated depression of ACh release from rat motor nerve terminals
Authors: Prior Chris , Singh Shila 
Published: January 2005

We have studied the inhibitory autoreceptor control of acetylcholine (ACh) release from rat motor nerve endings using an electrophysiological technique to quantify evoked ACh release in isolated hemidiaphragm muscles. Quantal ACh release (m) was estimated from the ratio of amplitudes of nerve evoked endplate currents and spontaneously occurring miniature endplate currents.
The nicotinic ACh receptor agonist cytisine (1 μM) decreased m at 0.5 Hz by around 20% but had no effect on m at 50 Hz. Changing the extracellular Ca2+ concentration from 1.8 mM to either 0.45 or 3.6 mM abolished the effect of cytisine on m at 0.5 Hz. The nicotinic ACh receptor antagonist hexamethonium (200 μM) increased m at 0.5 Hz by 15–20%.
The effects of cytisine and hexamethonium on m at 0.5 Hz were blocked by 10 μM verapamil, which itself significantly increased m. However, the effects of cytisine and hexamethonium on m at 0.5 Hz were not sensitive to 10 μM of the calmodulin antagonist, W‐7. This concentration of W‐7 attenuates effects on ACh release mediated by facilitatory prejunctional nicotinic ACh autoreceptors.
Our present observations are suggestive of actions of cytisine and hexamethonium to activate and inhibit respectively negative‐feedback prejunctional nicotinic ACh autoreceptors. Further, they strengthen the case for the existence of two separate and independent autoregulatory mechanisms for the control of ACh release from motor nerve terminals and give a preliminary insight into the cellular mechanism involved in the autoinhibition of ACh release.

British Journal of Pharmacology (2000) 129, 1067–1074; doi:10.1038/sj.bjp.0703161
The effect of P2 receptor antagonists and ATPase inhibition on sympathetic purinergic neurotransmission in the guinea‐pig isolated vas deferens
Authors: Sneddon P , Westfall T D , Todorov L D , Todorova S Mihaylova , Westfall D P , Nickel P , Kennedy C 
Published: January 2005

Intracellular microelectrodes were used to record the transmembrane potential and excitatory junction potentials (e.j.p.s) produced by sympathetic nerve stimulation (1 Hz) in smooth muscle cells of the guinea‐pig isolated vas deferens.
The symmetrical 3′‐urea of 8‐(benzamido)naphthalene‐1,3,5‐trisulphonic acid (NF023) produced a concentration‐dependent inhibition of e.j.p. magnitude (IC50=4.8×10−6 M), but had no effect on the resting membrane potential of the smooth muscle cells.
Pyridoxal‐5‐phosphate (P‐5‐P) also depressed e.j.p. magnitude in a concentration‐dependent manner, but was less potent than NF023 (IC50=2.2×10−5 M). At 10−4 M and above P‐5‐P significantly depolarized the smooth muscle cells.
The nucleoside triphosphatase inhibitor 6‐N,N‐diethyl‐D‐β,γ‐dibromomethyleneATP (ARL 67156) (5×10−5 M) significantly increased e.j.p. amplitude. ARL 67156 (10−4 M) further increased e.j.p. amplitude such that they often reached threshold for initiation of action potentials, causing muscle contraction and expulsion of the recording electrode.
After reduction of e.j.p.s by NF023 or P‐5‐P (both 10−5 M), subsequent co‐addition of ARL 67156 (10−4 M) significantly increased their magnitude.
The overflow of endogenous ATP evoked by field stimulation of sympathetic nerves (8 Hz, 1 min) was measured by HPLC and flurometric detection. ARL 67156 (10−4 M) enhanced ATP overflow by almost 700% compared to control.
We conclude that for electrophysiological studies NF023 is preferable to other P2X receptor antagonists such as pyridoxalphosphate ‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), suramin or P‐5‐P. Furthermore, breakdown of endogenous ATP by nucleoside triphosphatases is an important modulator of purinergic neurotransmission in the guinea‐pig vas deferens.

British Journal of Pharmacology (2000) 129, 1089–1094; doi:10.1038/sj.bjp.0703163
Effects of AMP derivatives on cyclic AMP levels in NG108‐15 cells
Authors: Ohkubo Satoko , Nakanishi Hironori , Kimura Junko , Matsuoka Isao 
Published: January 2005

In NG108‐15 neuroblastoma×glioma hybrid cells, ATP stimulates intracellular cyclic AMP formation, which is inhibited by both adenosine (P1) and P2 receptor antagonists. In the present study, we examined the effects of several AMP derivatives in NG108‐15 cells and mouse neuroblastoma N18TG‐2 cells.
Adenosine 2′‐monophosphate (A2P), adenosine 3′‐monophosphate (A3P) and adenosine 5′‐phosphosulphate (A5PS) increased cyclic AMP levels with similar concentration‐dependencies in NG108‐15 cells.
Increases in cyclic AMP by AMP derivatives were inhibited by the P2 receptor antagonist PPADS, but not by suramin. Effects of AMP derivatives were also inhibited by P1 receptor antagonists ZM241385, XAC, DPCPX and partially by alloxazine. The ecto‐nucleotidase inhibitor α,β‐methyleneADP was without effect.
In contrast, AMP derivatives did not change cyclic AMP levels in N18TG‐2 cells. Accumulation of cyclic AMP in N18TG‐2 cells was stimulated by adenosine A2 receptor agonists CGS21680 and NECA, but not by ATP or β,γ‐methyleneATP, agonists for cyclic AMP production in NG108‐15 cells.
Reverse transcription‐coupled polymerase chain reaction (RT–PCR) analyses revealed that N18TG‐2 cells express both A2A and A2B receptors, while NG108‐15 cells express mainly A2A receptors.
AMP derivatives did not affect the P2X and P2Y receptors expressed in NG108‐15 cells.
These results suggest that A2P, A3P and A5PS act as agonists for cyclic AMP production and that these compounds are valuable tools for determinating the mechanism of ATP‐stimulated cyclic AMP response in NG108‐15 cells.

British Journal of Pharmacology (2000) 129, 1244–1250; doi:10.1038/sj.bjp.0703168
The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A2A receptors
Authors: Yacoubi Malika El , Ledent Catherine , Ménard Jean‐François , Parmentier Marc , Costentin Jean , Vaugeois Jean‐Marie 
Published: January 2005

The locomotor stimulatory effects induced by caffeine (1,3,7‐trimethylxanthine) in rodents have been attributed to antagonism of adenosine A1 and A2A receptors. Little is known about its locomotor depressant effects seen when acutely administered at high doses. The roles of adenosine A1 and A2A receptors in these activities were investigated using a Digiscan actimeter in experiments carried out in mice. Besides caffeine, the A2A antagonist SCH 58261 (5‐amino‐7‐(β‐phenylethyl)‐2‐(8‐furyl)pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]pyrimidine), the A1 antagonist DPCPX (8‐cyclopentyl‐1,3‐dipropylxanthine), the A1 agonist CPA (N6‐cyclopentyladenosine) and A2A receptor knockout mice were used.
Caffeine had a biphasic effect on locomotion of wild‐type mice not habituated to the open field, stimulating locomotion at 6.25–25 mg kg−1 i.p. doses, while depressing it at 100 mg kg−1. In sharp contrast, caffeine dose‐dependently decreased locomotion in A2A receptor knockout mice over the whole range of tested doses.
The depressant effects induced by high doses of caffeine were lost in control CD1 mice habituated to the open field.
The A1 agonist CPA depressed locomotion at 0.3–1 mg kg−1 i.p. doses.
The A1 antagonist DPCPX decreased locomotion of A2A receptor knockouts and CD1 mice at 5 mg kg−1 i.p. and 25 mg kg−1 i.p. respectively.
DPCPX (0.2–1 mg kg−1 i.p.) left unaltered or even reduced the stimulant effect of SCH 58261 (1–3 mg kg−1 i.p.) on CD1 mice.
These results suggest therefore that the stimulant effect of low doses of caffeine is mediated by A2A receptor blockade while the depressant effect seen at higher doses under some conditions is explained by A1 receptor blockade.

British Journal of Pharmacology (2000) 129, 1465–1473; doi:10.1038/sj.bjp.0703170
Respiratory actions of tachykinins in the nucleus of the solitary tract: characterization of receptors using selective agonists and antagonists
Authors: Mazzone Stuart B , Geraghty Dominic P 
Published: January 2005

The respiratory response to microinjection of tachykinins and analogues into the commissural nucleus of the solitary tract (cNTS) of urethane‐anaesthetized rats was investigated in the presence and absence of selective tachykinin NK1, NK2 and NK3 antagonists (RP 67580, SR 48968 and SR 142801, respectively).
All tachykinins, except for the selective NK2 agonist, [Nle10]‐NKA(4‐10), increased tidal volume (VT). The rank potency order of naturally‐occurring tachykinins was neurokinin A (NKA)substance P (SP)>>NKB, whereas the rank order for selective analogues was senktideseptide>> [Sar9,Met(O2)11]‐SP>>[Nle10]‐NKA(4‐10). Septide (NK1‐selective) and senktide (NK3‐selective) were 22 fold more potent (pD2∼12) at stimulating VT than SP (pD2∼10.5).
Tachykinin agonists produced varying degrees of respiratory slowing, independent of changes in VT. At doses producing maximum stimulation of VT, agonists induced either a mild (<10 breaths min−1 decrease; SP and septide), moderate (10–25 breaths min−1 decrease; NKA, NKB and [Sar9,Met(O2]‐SP) or severe (∼40 breaths min−1 decrease; senktide) bradypnoea. [Nle10]‐NKA(4‐10) produced a dose‐dependent bradypnoea without affecting VT.
RP 67580 significantly attenuated the VT response to SP (33 pmol) and NKA (10 pmol) but not NKB (100 pmol). In the presence of RP 67580, the mild bradypnoeic response to NKB was significantly enhanced whereas SP and NKA induced a bradypnoea which was not observed in the absence of RP 67580. SR 48968 had no effect on the VT response to SP or NKB, markedly enhanced the VT response to NKA and completely blocked the bradypnoeic response to [Nle10]‐NKA(4‐10). Only SR142801 attenuated the VT response to NKB.
The present data suggest that all three tachykinin receptors (NK1, NK2 and NK3) are present in the cNTS and are involved in the central control of respiration.

British Journal of Pharmacology (2000) 129, 1121–1131; doi:10.1038/sj.bjp.0703172
Nitrergic relaxation of the mouse gastric fundus is mediated by cyclic GMP‐dependent and ryanodine‐sensitive mechanisms
Authors: Selemidis Stavros , Cocks Thomas M 
Published: January 2005

Ryanodine‐sensitive, Ca2+ release (‘Ca2+ sparks’) from the sarcoplasmic reticulum (SR) can activate plasmalemmal Ca2+‐activated K+ channels (KCa) to cause membrane hyperpolarization and smooth muscle relaxation. Since cyclic guanosine monophosphate (cyclic GMP) can modulate Ca2+ spark activity, the aim of the present study was to determine if Ca2+ spark‐like events are involved in NO‐dependent, NANC relaxations to electrical field stimulation (EFS) of mouse, longitudinal smooth muscle of the gastric fundus in isolated strips contracted to ∼40% of their maximum contraction.
NANC relaxations to EFS were almost abolished by both the NO synthase inhibitor, NG‐nitro‐L‐arginine (L‐NOARG; 100 μM) and the guanylate cyclase inhibitor, 1‐H‐oxodiazol‐[1,2,4]‐[4,3‐α] quinoxaline‐1‐one (ODQ; 10 μM). Also, ODQ abolished relaxations to the NO donor, sodium nitroprusside (SNP; 1 nM–30 μM). NANC relaxations and SNP‐evoked relaxations were both partly ryanodine (10 μM)‐ and nifedipine (0.3 μM)‐sensitive, but in each case, the inhibitory effects of ryanodine and nifedipine were additive.
Apamin (1 μM), charybdotoxin (0.1 μM), iberiotoxin (0.1 μM), tetraethylammonium (TEA; 1 mM), glibenclamide (10 μM) and 4‐aminopyridine (1 mM) had no effect on either NANC‐ or SNP‐evoked relaxations, the latter of which were also unaffected by high extracellular K+ (68 mM).
Caffeine (0.1–1 mM) caused concentration‐dependent relaxations of gastric fundus which were inhibited by ryanodine but unaffected by L‐NOARG.
Relaxation to ATP (30 μM) was abolished by nifedipine, partly inhibited by apamin and ryanodine, but was unaffected by L‐NOARG.
In conclusion, the results of the present study show that nitrergic relaxations in the mouse longitudinal gastric fundus occur via a cyclic GMP‐activated ryanodine‐sensitive mechanism, which does not appear to involve activation of K+ channels.

British Journal of Pharmacology (2000) 129, 1315–1322; doi:10.1038/sj.bjp.0703174
Active immunization with angiotensin I peptide analogue vaccines selectively reduces the pressor effects of exogenous angiotensin I in conscious rats
Authors: Gardiner S M , Auton T R , Downham M R , Sharp H L , Kemp P A , March J E , Martin H , Morgan P J , Rushton A , Bennett T , Glover J F 
Published: January 2005

Male, Sprague‐Dawley rats were actively immunized with novel angiotensin vaccines, and their pressor responses to exogenous angiotensin I (AI) and angiotensin II (AII) were assessed in vivo. Serum antibody titres were also measured.
The most effective vaccine consisted of an AI analogue conjugated with a tetanus toxoid carrier protein and adjuvanted with aluminium hydroxide. When this vaccine was injected on days 0, 21 and 42, pressor responses to AI on day 63 were significantly inhibited (maximum, 8.9 fold shift), but responses to AII were unaffected. The anti‐angiotensin antibody titre was increased 32,100 fold, and, uniquely, these antibodies also cross‐reacted with angiotensinogen.
These findings indicate that active immunization against AI may be a useful approach for treating cardiovascular disorders involving the renin‐angiotensin system.

British Journal of Pharmacology (2000) 129, 1178–1182; doi:10.1038/sj.bjp.0703178
Both α1A‐ and α1B‐adrenergic receptor subtypes couple to the transient outward current (ITo) in rat ventricular myocytes
Authors: Homma Nobuo , Hirasawa Akira , Shibata Katsushi , Hashimito Keitaro , Tsujimoto Gozoh 
Published: January 2005

Regulation of transient outward current (ITo) by α1‐adrenergic (α1AR) plays a key role in cardiac repolarization. α1ARs comprise a heterogeneous family; two natively expressed subtypes (α1A and α1B) and three cloned subtypes (α1a, α1b and α1d) can be distinguished. We have examined the electrophysiological role of each α1AR subtype in regulating ITo in isolated rat ventricular myocytes.
Reverse transcription‐PCR study revealed the presence of three subtype mRNAs (α1a, α1b and α1d) in rat myocytes.
Radioligand binding assay using [125I]‐HEAT showed that the inhibition curves for α1AAR‐selective antagonists (WB4101, 5‐methylurapidil, (+)‐niguldipine and KMD‐3213) in rat ventricles best fit a two‐site model, with 30% high and 70% low affinity binding sites. The high affinity sites were resistant to 100 μM chloroethylclonidine (CEC), while the low affinity sites were highly inactivated by CEC.
Whole cell voltage clamp study revealed that methoxamine reduced a 4‐aminopyridine(4‐AP)‐sensitive component of ITo in the isolated rat ventricle myocytes. Lower concentrations of KMD‐3213 (1 nM) or 5‐MU (10 nM) did not affect the methoxamine‐induced reduction of ITo. On the other hand, CEC treatment (100 μM) of isolated myocytes reduced the methoxamine‐induced reduction of ITo by 46%, and the remaining response was abolished by lower concentrations of KMD‐3213 or 5‐MU.
The results indicate that rat ventricular myocytes express transcripts of the three α1AR subtypes (α1a, α1b and α1d); however, two pharmacologically distinct α1AR subtypes (α1A and α1B) are predominating in receptor populations, with approximately 30% α1AAR and 70% α1BAR. Although both α1A and α1BAR subtypes are coupled to the cardiac ITo, α1BARs predominantly mediate α1AR‐induced effect.

British Journal of Pharmacology (2000) 129, 1113–1120; doi:10.1038/sj.bjp.0703179
Characterization of human recombinant α2A‐adrenoceptors expressed in Chinese hamster lung cells using intracellular Ca2+ changes: evidence for cross‐talk between recombinant α2A‐ and native α1‐adrenoceptors
Authors: Reynen P H , Martin G R , Eglen R M , MacLennan S J 
Published: January 2005

Human α2A‐adrenoceptors expressed in Chinese hamster lung (CHL) fibroblasts have been pharmacologically characterized by measuring intracellular calcium (Ca2+i) changes using the Ca2+‐sensitive dye Fluo3‐AM, in conjunction with a fluorometric imaging plate reader (FLIPR).
Several α‐adrenoceptor agonists were examined including the α2‐adrenoceptor agonists UK‐14304, B‐HT 920, dexmedetomidine and A‐54741, the selective α1‐adrenoceptor agonist phenylephrine and the non‐selective adrenergic agonist noradrenaline. Of these only noradrenaline (mean pEC50=6.49) and A‐54741 (6.90) evoked changes in Ca2+i; A‐54741 was a partial agonist relative to noradrenaline, achieving only 33% of the noradrenaline maximum.
Ca2+i changes induced by noradrenaline and A‐54741 were antagonized by the α2‐selective antagonist rauwolscine (10 nM) and by the α1‐selective antagonists prazosin (0.1 nM) and doxazosin (1.0 nM).
Phenylephrine (100 μM) and UK‐14304 (10 μM) alone were ineffective in causing Ca2+i increase. In the presence of a fixed concentration of UK‐14304 (3.0 μM), phenylephrine induced concentration‐dependent increases in Ca2+i (mean pEC50=5.33). In the presence of phenylephrine (30.0 μM) UK‐14304 induced Ca2+i release (pEC50=6.92). The effects of phenylephrine were abolished by prazosin (1.0 nM) or rauwolscine (100 nM).
In saturation radioligand binding experiments using membranes of parental (non‐transfected) CHL cells there was a small, specific binding of [3H]‐prazosin (Bmax=24 fmol mg protein−1; pKD=10.24).
Collectively, these data suggest that α‐adrenoceptor agonist‐induced Ca2+i release in CHL fibroblasts transfected with the human α2A‐adrenoceptor is dependent upon co‐activation of the recombinant receptor and a native α1‐adrenoceptor.

British Journal of Pharmacology (2000) 129, 1339–1346; doi:10.1038/sj.bjp.0703184
Role of gap junctions and EETs in endothelium‐dependent hyperpolarization of porcine coronary artery
Authors: Edwards G , Thollon C , Gardener M J , Félétou M , Vilaine J ‐P , Vanhoutte P M , Weston A H 
Published: January 2005

The effects of endothelium‐derived hyperpolarizing factor (EDHF: elicited using substance P or bradykinin) were compared with those of 11,12‐EET in pig coronary artery. Smooth muscle cells were usually impaled with microelectrodes through the adventitial surface.
Substance P (100 nM) and 11,12‐EET (11,12‐epoxyeicosatrienoic acid; 3 μM) hyperpolarized endothelial cells in intact arteries. These actions were unaffected by 100 nM iberiotoxin but were abolished by charybdotoxin plus apamin (each 100 nM).
Substance P (100 nM) and bradykinin (30 nM) hyperpolarized intact artery smooth muscle; Substance P had no effect after endothelium removal.
11,12‐EET hyperpolarized de‐endothelialized vessels by 12.6±0.3 mV, an effect abolished by 100 nM iberiotoxin. 11,12‐EET hyperpolarized intact arteries by 18.6±0.8 mV, an action reduced by iberiotoxin, which was ineffective against substance P. Hyperpolarizations to 11,12‐EET and substance P were partially inhibited by 100 nM charybdotoxin and abolished by further addition of 100 nM apamin.
30 μM barium plus 500 nM ouabain depolarized intact artery smooth muscle but responses to substance P and bradykinin were unchanged. 500 μM gap 27 markedly reduced hyperpolarizations to substance P and bradykinin which were abolished in the additional presence of barium plus ouabain.
Substance P‐induced hyperpolarizations of smooth muscle cells immediately below the internal elastic lamina were unaffected by gap 27, even in the presence of barium plus ouabain.
In pig coronary artery, 11,12‐EET is not EDHF. Smooth muscle hyperpolarizations attributed to ‘EDHF’ are initiated by endothelial cell hyperpolarization involving charybdotoxin‐ (but not iberiotoxin) and apamin‐sensitive K+ channels. This may spread electrotonically via myoendothelial gap junctions but the involvement of an unknown endothelial factor cannot be excluded.

British Journal of Pharmacology (2000) 129, 1145–1154; doi:10.1038/sj.bjp.0703188