bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bradykinin receptors in mouse and rat isolated superior cervical ganglia
Authors: Seabrook G.R. , Bowery B.J. , Hill R.G. 
Published: July 2012

The ability of bradykinin and its analogues to depolarize rat and mouse superior cervical ganglia was studied by use of in vitro grease‐gap recording techniques, and the ability of antagonists selective for bradykinin receptor subtypes to block their effects was examined.
Bradykinin (μm) depolarized ganglia from both species, although the magnitude of the maximal response was less in mouse (15 ± 5%, n = 7) than rat tissue (33 ± 6%, n = 7), relative to muscarine (1μm).
Interleukin 1β (30 u ml−1 for 18 h at 37°C) increased the depolarization caused by bradykinin (3μm) in mouse ganglia from 15% to 54% (P<0.001, n=12). Responses to the B1 receptor agonist, [des‐Arg10]‐kallidin (3μm) were similarly potentiated but this was only detected after inhibition of peptidase activity with 10FM captopril (4% to 35%, n = 5).
In ganglia from both species the rank order of agonist potency was bradykinin = [Lys0]‐bradykinin >> [des‐Arg10]‐kallidin. However, like responses to [des‐Arg10]‐kallidin in mouse tissue, both the potency of bradykinin and the maximal depolarization achieved (EC50 = 912 nM; 80%, n = 11) was enhanced following inhibition of angiotensin converting enzyme with 10μm captopril (EC50 = 50 nM; 135%, n = 4).
Responses to bradykinin were selectively antagonized by the B2 receptor antagonist, Hoe 140 but not by the B1 antagonist, [Leu8]‐bradykinin1–8. From Schild analysis the pA2 value for Hoe 140 in mouse tissue was 9.65, although the slope of the regression line was significantly greater than unity, indicating non‐competitive kinetics (slope = 1.88 ± 0.18, n = 9). The depolarization caused by [Lys0]‐bradykinin was also antagonized by Hoe 140 (3 nM).
Thus the predominant bradykinin receptor in mouse superior cervical ganglia is compatible with a B2 subtype. Furthermore the depolarizations caused by B1 and B2 agonists in this tissue can be increased following exposure to interleukin 1β, and by blocking peptide degradation with captopril.
Effects of endothelin receptor antagonism with bosentan on peripheral nerve function in experimental diabetes
Authors: Stevens Elizabeth J. , Tomlinson David R. 
Published: July 2012

The effects of the non‐selective endothelin (ET) receptor (ETA/ETB) antagonist, bosentan, on sciatic nerve dysfunction in experimental diabetes were investigated.
Rats with 5–6 weeks untreated streptozotocin‐diabetes exhibited characteristic slowed motor nerve conduction velocity (mean ± s.d., 36.6 ± 3.4 m s−1) and nerve laser Doppler flux (197 ±64 arbitrary units) compared to age‐matched control animals (42.7 ± 2.4 m s−′ and 398 ± 77 arbitrary units, respectively). Preventative treatment of diabetic rats with bosentan at 100 mg kg−1 day−1 p.o. attenuated both these deficits (39.7 ± 3.0 m s−1 and 305 ± 56 arbitrary units, respectively) without affecting mean arterial pressure.
In control and untreated diabetic rats, ET‐1, 1 nmol kg−1 i.v., caused an initial hypotension (duration, 30 ±13 and 26 ± 9 s, respectively; change in mean arterial pressure, −27 ±13 and − 25 ± 7 mmHg, respectively) followed by prolonged hypertension (change in mean arterial pressure, 52 ± 18 and 31 ± 5 mmHg, respectively). Effectiveness of the chronic bosentan treatment was demonstrated by inhibition of the hypotensive response to ET‐1 in treated diabetic rats (duration, 5 ± 2 s; change in mean arterial pressure, − 4 + 2 mmHg) although the hypertension was unaltered (change in mean arterial pressure, 32 + 9 mmHg).
Acute i.v. administration of 10mg kg−1 bosentan caused variable and transient rises in nerve laser Doppler flux in control (78 ± 63 arbitrary units) and untreated diabetic rats (93 ± 77 arbitrary units). Acute bosentan blocked the hypotensive response to subsequent ET‐1 administration and attenuated the later hypertension (change in mean arterial pressure, 21 ±9 mmHg in control, 29 ±10 mmHg in diabetic).
Our results indicate that oral treatment of diabetic rats with an ET receptor antagonist can improve sciatic nerve perfusion and conduction, suggesting that the vasoconstrictor action of endogenous ET may contribute to peripheral nerve dysfunction in experimental diabetes.
Further evidence from functional studies for somatostatin receptor heterogeneity in guinea‐pig isolated ileum, vas deferens and right atrium
Authors: Feniuk W. , Dimech J. , Jarvie E.M. , Humphrey P.P.A. 
Published: July 2012

Somatostatin (SRIF) causes a concentration‐dependent inhibition of neurotransmission in guinea‐pig ileum and vas deferens as well as negative inotropy in guinea‐pig isolated right atrium. The SRIF receptors mediating these effects have now been further characterized by use of the peptides BIM‐23027, BIM‐23056 and L‐362855, reported as selective for the recombinant SRIF receptor types, sst2, sst3 and sst5, respectively.
BIM‐23027 was a highly potent agonist at causing an inhibition of neurotransmission in the guinea‐pig ileum (EC50 value 1.9 nM), being about 3 times more potent than SRIF (EC50 value 6.8 nM). In contrast, in both guinea‐pig vas deferens and right atrial preparations, BIM‐23027 was a relatively weak agonist being at least 30–100 times weaker than SRIF. In guinea‐pig atria, BIM‐23027 (3 μu) antagonized the negative inotropic action of SRIF28 (apparent pAb = 5.9±0.1) but had no effect on the negative inotropic action of cyclohexyladenosine.
The inhibitory effect of BIM‐23027 in the guinea‐pig ileum was readily desensitized. Prior exposure to BIM‐23027 (0.3 μm) markedly attenuated the inhibitory effect of SRIF but had no effect on the inhibitory action of clonidine suggesting that BIM‐23027 and SRIF act via a common receptor mechanism.
L‐362855 caused a concentration‐dependent inhibition of neurotransmission in both the guinea‐pig ileum and vas deferens as well as causing negative inotropy in the guinea‐pig atrium but was at least 30–100 times weaker than SRIF. In guinea‐pig isolated atria, L‐362855 (3 μm) did not antagonize the negative inotropic action of SRIF28.
BIM‐23056 in concentrations up to 1 μm was inactive as an agonist in guinea‐pig isolated ileum, vas deferens and atrium and did not antagonize the inhibitory actions of SRIF in any of these preparations.
The results from this study support our previous contention that the sst2 receptor type mediates inhibition of neurotransmission by SRIF in the guinea‐pig ileum. The SRIF receptor type mediating inhibition of neurotransmission in the guinea‐pig vas deferens appears different, but similar, to that mediating negative inotropy in the atrium. However the characteristics of these latter receptors appear different from that of the recombinant sst2, sst3 and sst5 receptors for SRIF described for rat and man.
Glucocorticoid‐induced annexin 1 secretion by monocytes and peritoneal leukocytes
Authors: Coméra Christine , Russo‐Marie Frarçise 
Published: July 2012

We have studied the ability of the glucocorticoid, dexamethasone, to induce annexin 1 secretion by either human blood monocytes or rat peritoneal leukocytes.
The in vivo treatment of rats with dexamethasone (1.25 mg kg−1) selectively induced secretion of annexin 1 by peritoneal leukocytes, as assessed by incubating these cells in culture medium. Annexin 1 secretion was also induced in human cultured monocytes, in vitro, by 10−6m dexamethasone.
Annexin 1 secretion was inhibited in the presence of 20 mM NH4C1 or by conducting the experiments at 18°C. In contrast, it was not inhibited by monensin, nocodazole or brefeldin A.
The time necessary for annexin 1 synthesis and secretion was less than 15 min.
These data indicate that glucocorticoids induce annexin 1 secretion by monocytes or peritoneal leukocytes. Because it is not inhibited by monensin, nocodazole or brefeldin A and it is rapid, annexin 1 secretion seems to occur by the secretory pathway similar to that used by several cytosolic proteins such as interleukin‐iβ.
In situ hybridization studies of prostacyclin receptor mRNA expression in various mouse organs
Authors: Oida Hiroji , Namba Tsunehisa , Sugimoto Yukihiko , Ushikubi Fumitaka , Ohishi Hitoshi , Ichikawa Atushi , Narumiya Shuh 
Published: July 2012

Expression of prostacyclin receptor (IP receptor) mRNA was examined in various mouse organs, and the cells expressing IP receptor mRNA were identified by in situ hybridization studies. Co‐localization of mRNA for the IP receptor with that for preprotachykinin A (PPTA), a precursor protein for substance P, with mRNA for the prostaglandin E receptor subtypes (EP1, EP3 and EP4), and with renin mRNA, was examined by double in situ hybridization studies in the dorsal root ganglion and kidney, respectively.
IP receptor mRNA was expressed in the thymus and spleen. Expression in the thymus was found exclusively in the medulla, where mature thymocytes expressed transcripts for the IP receptor. Expression in the spleen was found as scattered signals over the white pulp and as punctate signals in the red pulp. The former was found in splenic lymphocytes and the latter in megakaryocytes.
IP receptor mRNA was also expressed in the vascular tissues of various organs such as the aorta, coronary arteries, pulmonary arteries and the cerebral arteries, where its expression was confined to smooth muscle cells. No expression was found in veins. In the kidney, IP receptor mRNA was detected in the interlobular arteries and glomerular arterioles but not in the juxtaglomerular (JG) cells which were labelled with the renin mRNA probe.
IP receptor mRNA was expressed in about 40% of the neurones in the dorsal root ganglion. Both small‐ and large‐sized neurones were labelled but no labelling was found in the glia. Expression of PPT A mRNA was found in about 30% of total neurones. About 70% of these neurones expressed IP receptor mRNA, and about half of the IP receptor‐positive neurones expressed PPTA mRNA. In addition to IP mRNA, mRNAs for EP1, EP3 and EP4 receptors were expressed in about 30%, 50% and 20%, respectively, of the dorsal root ganglion neurones. About 25%, 41% and 24% of the IP receptor‐positive neurones co‐expressed the EP1, EP3 and EP4 receptor, respectively.
These results not only verified IP receptor expression in various cells and tissues known to be sensitive to prostacyclin, but also revealed its expression in other systems, which urges the study of the actions of prostacyclin in these tissues. They also indicated that the actions of prostacyclin on blood vessels and platelets are mediated by the same type of receptor. Absence of IP receptor mRNA in the JG cells suggests that the action of prostacyclin on renin release may be indirect.
Effect of chronic morphine treatment on transmitter release from sympathetic varicosities of the mouse vas deferens
Authors: Lavidis Nickolas A. 
Published: July 2012

Transmitter release from sympathetic varicosities of mouse vasa deferentia removed from animals which were chronically treated with morphine for 7 to 9 days has been evaluated.
In control preparations increasing the extracellular calcium concentration ([Ca2+]o) from 1 to 2 mM increased transmitter release by 3 fold while increasing [Ca2+]o from 6 to 8 mM increased transmitter release by about 0.9 fold. Introduction of morphine (1.0 μm) produced a uniform decrease in transmitter release, shifting the relationship between transmitter release and [Ca2+]o to the right.
Only sympathetic varicosities with probabilities of transmitter release greater than 0.01 were chosen for this study. In these varicosities the decrease in transmitter release induced by morphine in control preparations (bathed in [Ca2+]o 2.0 mm) was not observed following 7 to 9 days of morphine treatment. When the morphine was acutely withdrawn from these preparations transmitter release was more than 6 times the average level of transmitter release from control preparations.
The morphine induced increase in facilitation of transmitter release while stimulating with short trains of nerve impulses was not observed when the preparations were removed from animals which had been exposed to morphine for 7 to 9 days. When these preparations were acutely withdrawn from morphine there was a further decrease in the level of facilitation and a significant increase in depression of transmitter release when compared to control.
The morphine induced decrease in probability of transmitter release when naive sympathetic varicosities in vitro were bathed with morphine (1 μm) was not observed following chronic morphine treatment of the animals for 7 to 9 days. When the morphine was acutely withdrawn from chronically morphine treated preparations the underlying increase in probabilities of transmitter release of sympathetic varicosities was unmasked.
Phosphorylation‐ and voltage‐dependent inhibition of neuronal calcium currents by activation of human D2(short) dopamine receptors
Authors: Brown Nicola A. , Seabrook Guy R. 
Published: July 2012

Activation of human D2(8) dopamine receptors with quinpirole (10 nM) inhibits ω‐conotoxin GVIa‐sensitive, high‐threshold calcium currents when expressed in differentiated NG108‐15 cells (55% inhibition at +10 mV). This inhibition was made irreversible following intracellular dialysis with the non‐hydrolysable guanosine triphosphate analogue GTP‐γ‐S (100 μM), and was prevented by pretreatment with pertussis toxin (1 μg ml−1 for 24 h).
Stimulation of protein kinase C with the diacylglycerol analogue, 1‐oleoyl‐2‐acetyl‐sn‐glycerol (100 μM), also attenuated the inhibition of the sustained calcium current but did not affect the receptor‐mediated decrease in rate of current activation. Similarly, okadaic acid (100 nM), a protein phosphatase 1/2A inhibitor, selectively occluded the inhibition of the sustained current.
The depression of calcium currents by quinpirole (10 nM) was enhanced following intracellular dialysis with 100 μM cyclic adenosine monophosphate (cyclic AMP, 72.8 ±9.8% depression), but was not mimicked by the membrane permeant cyclic GMP analogue, Sp‐8‐bromoguanosine‐3′, 5′:cyclic monophosphorothioate (100 μM).
Inhibition of calcium currents was only partly attenuated by 100 ms depolarizing prepulses to +100 mV immediately preceding the test pulse. However, following occlusion of the sustained depression with okadaic acid (100 nM) the residual kinetic slowing was reversed in a voltage‐dependent manner (P<0.05).
Thus pertussis toxin‐sensitive G‐proteins liberated upon activation of human D2(short) dopamine receptors inhibited high‐threshold calcium currents in two distinct ways. The decrease in rate of calcium current activation involved a voltage‐dependent pathway, whereas the sustained inhibition of calcium current involved, in part, the voltage‐resistant phosphorylation by cyclic AMP‐dependent protein kinases and subsequent dephosphorylation by protein phosphatases 1/2A.
Induction of a novel form of hippocampal long‐term depression by muscimol: involvement of GABAA but not glutamate receptors
Authors: Akhondzadeh S. , Stone T.W. 
Published: July 2012

Unlike long‐term potentiation, long‐term depression (LTD) in the central nervous system remains poorly understood. The present study was undertaken to investigate the role of GABAA receptors in LTD and synaptic plasticity.
Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz).
Muscimol induced a time‐ and concentration‐dependent LTD of the amplitude of orthodromic potentials. Increasing the stimulation frequency from 0.01 Hz to 1 Hz for 10 s reversed the LTD induced by muscimol. Muscimol also induced LTD in the absence of electrical stimulation.
Adenosine decreased the spike size in a concentration‐dependent manner, but failed to induce LTD.
Alphaxalone and 5α‐pregnan‐3α‐ol‐20‐one at concentrations that did not have any effect themselves on the population spike (0.5 and 1 μM), potentiated the inhibitory effect of muscimol on the population spike size, including concentrations which were not effective by themselves. Both steroids were able to potentiate the ability of muscimol to induce LTD.
Bicuculline, 5 μM, reversed the LTD induced by muscimol, 10 μM.
The NMDA receptor antagonist (±)‐2‐amino‐5‐phosphonopentanoic acid (2‐AP5), the NMDA/ metabotropic antagonist 2‐AP3 and selective metabotropic antagonist L‐(+)‐2‐amino‐3‐phosphonopro‐pionic acid (L(+)‐AP3) failed to modify the LTD. Similarly, quisqualic acid and (1S, 3R)‐aminocyclopentane dicarboxylic acid (ACPD) a selective agonist at metabotropic receptors did not induce LTD or short‐term depression, whereas kynurenic acid prevented the reversal of the LTD obtained at 1 Hz.
It is concluded that LTD can be induced by the selective activation of GABAA receptors. The lack of involvement of glutamate receptors in our protocol confirms the unique nature of the LTD described here. The phenomenon of GABA‐induced LTD and its reversal by 1 Hz stimulation may represent a novel type of long‐lasting depression by which inhibitory interneurones can modulate pyramidal cell excitability in a frequency‐dependent manner.
A role for Q type Ca2+ channels in neurotransmission in the rat urinary bladder
Authors: Frew Robert , Lundy Paul M. 
Published: July 2012

In isolated bladder strips of the rat, a substantial component (46%) of the Ca2+‐dependent contractile response to electrical field stimulation (5 Hz) was resistant to combined block of both N and P type Ca2+ channels by ω‐conotoxin‐GVIA (300 nM) and ω‐agatoxin‐IVA (100 nM) respectively.
The resistant portion (non‐N, non‐P) was sensitive to ω‐conotoxin‐MVIIC (3 μM), which in addition to N and P also blocks Q type channels at this concentration. ω‐Conotoxin‐MVIIC administered alone, inhibited the neurogenic response to the same degree as that observed in the combined presence of ω‐agatoxin‐IVA, ωconotoxin‐GVIA and ω‐conotoxin‐MVIIC.
ω‐Agatoxin‐IVA (100 nM), a concentration that fully inhibits P type channels, had a negligible effect on the neurogenic response. Following blockade of N type Ca2+ channels with ω‐conotoxin‐GVIA (300 μM), ω‐agatoxin‐IVA (3 μM) (a concentration well above that used to block P channels, inhibits Q type channels, but spares N type channels), inhibited the residual response to the same degree as ω‐conotoxin‐MVIIC alone.
Results suggest that neurotransmission in rat urinary bladder is supported by both N and Q type Ca2+ channels.
Histamine H1 receptor occupancy in human brains after single oral doses of histamine H1 antagonists measured by positron emission tomography
Authors: Yanai Kazuhiko , Ryu Jong Hoon , Watanabe Takehiko , Iwata Ren , Ido Tatsuo , Sawai Yoneichi , Ito Kazumi , Itoh Masatoshi 
Published: July 2012

Histamine H1 receptor occupancy in the human brain was measured in 20 healthy young men by positron emission tomography (PET) using [11C]‐doxepin.
(+)‐Chlorpheniramine, a selective and classical antihistamine, occupied 76.8±4.2% of the averaged values of available histamine H1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Intravenous administration of 5 mg (+)‐chlorpheniramine almost completely abolished the binding of [uC]‐doxepin to H1 receptors (H1 receptor occupancy: 98.2±1.2%).
Terfenadine, a nonsedative antihistamine, occupied 17.2±14.2% of the available H1 receptors in the human frontal cortex after its administration in a single oral dose of 60 mg.
There was no correlation between H1 receptor occupancy by terfenadine and the plasma concentration of the active acid metabolite of terfenadine in each subject.
PET data on human brain were essentially compatible with those on H1 receptor occupancy in guinea‐pig brain determined by in vivo binding techniques, although for the same H1 receptor occupancy the dose was less in human subjects than in guinea‐pigs.
The PET studies demonstrated the usefulness of measuring H1 receptor occupancy with classical and second‐generation antihistamines in human brain to estimate their unwanted side effects such as sedation and drowsiness quantitatively.
Effects of divalent cations and La3+ on contractility and ecto‐ATPase activity in the guinea‐pig urinary bladder
Authors: Ziganshin Airat U. , Ziganshina Lilia E. , Hoyle Charles H.V. , Burnstock Geoffrey 
Published: July 2012

Several cations (Ba2+, Cd2+, Co2+, Cu2+, Mn2+, Ni2+, Zn2+ and La3+, all as chloride salts, 1–1000 μm) were tested in the guinea‐pig urinary bladder for their ability to: (i) modify contractile responses to electrical field stimulation (EFS), ATP, α,β‐methylene ATP (α,β‐meATP), carbachol (CCh), and KCl; (ii) affect ecto‐ATPase activity.
Ba2+ (10–1000 μm) concentration‐dependently potentiated contractile responses evoked by EFS (4–16 Hz), ATP (100 μm), α,β‐meATP (1 μm), CCh (0.5 μm), and KCl (30 mm). Ni2+ at concentrations of 1–100 μm also potentiated contractility of the urinary bladder, but at concentrations tested its effect was not concentration‐dependent. Cu2+ at a concentration of 10 μm and Cd2+ at a concentration of 1 μm potentiated responses to all stimuli, except KCl. Ni2+ at a concentration of 1000 μm and Cd2+ at a concentration of 100 μm inhibited contractions evoked by all stimuli, and at a concentration of 1000 μm Cd2+ abolished any contractions. Responses to ATP and α,β‐meATP were selectively inhibited by Cu2+, Zn2+ or La3+, each at a concentration of 1 mm.
Cu2+, Ni2+, Zn2+ and La3+ (100–1000 μm) concentration‐dependently inhibited ecto‐ATPase activity in the urinary bladder smooth muscle preparations, while Ba2+ and Mn2+ were without effect, and Cd2+ and Co2+ caused significant inhibition only at a concentration of 1000 μm.
There was no correlation between the extent of ecto‐ATPase inhibition and the effect on contractile activity of any of the cations.
In conclusion, the ability of some divalent cations to inhibit ecto‐ATPase activity and to potentiate or inhibit contractile responses in the guinea‐pig urinary bladder appear to be independent effects.