bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transepithelial water movement in response to carbamazepine, chlorpropamide and demeclocycline in toad urinary bladder
Authors: Hirji M.R. , Mucklow J.C. 
Published: July 2012

Osmotic water movement across toad isolated hemibladders was measured by a gravimetric method.
The influence of carbamazepine, chlorpropamide and demeclocycline on the antidiuretic hormone (ADH)‐induced water flow rate was examined.
No antidiuretic activity due to carbamazepine alone was observed but a slight inhibition due to ADH‐induced water flow was observed in the presence of carbamazepine over a selected dose‐range. This was unexpected and is inconsistent with data from in vivo studies in man.
Chlorpropamide potentiated ADH‐induced water flow, in keeping with the hypothesis that chlorpropamide sensitizes the renal tubules to ADH‐induced water flow.
Demeclocycline inhibited ADH‐induced water flow. The mechanism of action remains unclear.
The non‐peptide tachykinin antagonist, CP‐96,345, is a potent inhibitor of neurogenic inflammation
Authors: Lembeck Fred , Donnerer Josef , Tsuchiya Megumi , Nagahisa Atsushi 
Published: July 2012

Release of the tachykinin, substance P, from the peripheral terminals of polymodal afferent C‐fibres is thought to be largely responsible for the vasodilatation and plasma protein extravasation described as neurogenic inflammation. The effects of CP‐96,345, a non‐peptide antagonist at the substance P (NK1) receptor, on these vascular reactions were investigated in the rat.
Intravenously (i.v.) injected CP‐96,345 (0.4–3.0 μmol kg−1) prevented the drop in blood pressure, a measure of the peripheral vasodilatation, evoked by substance P and neurokinin A in a dose‐ and time‐dependent manner, but did not affect that elicited by the non‐tachykinin peptides calcitonin gene‐related peptide and vasoactive intestinal polypeptide.
Plasma protein extravasation evoked by i.a. infusion of substance P, antidromic stimulation of the saphenous or the vagus nerve, and stimulation of cutaneous afferent nerves with mustard oil, were each significantly inhibited by CP‐96,345 (3.0–9.0 μmol kg−1, i.v.). Furthermore, CP‐96,345 was orally active in blocking mustard oil‐induced plasma extravasation with an ED50 of 10 μmol kg−1.
The inhibition of substance P‐induced vasodilatation and of neurogenic plasma extravasation by CP‐96,345 was stereospecific as the inactive isomer CP‐96,344 (2R, 3R enantiomer of CP‐96,345) had no effect.
Thus CP‐96,345 is a specific, highly potent, long‐acting and orally active inhibitor of tachykinin‐mediated neurogenic inflammation.
Different in vivo properties of three new inhibitors of catechol O‐methyltransferase in the rat
Authors: Männistö Pekka T. , Tuomainen Päivi , Tuominen Raimo K. 
Published: July 2012

We compared three new catechol O‐methyltransferase (COMT) inhibitors (OR‐611, Ro 40–7592 and CGP 28014; 10 and 30 mg kg−1, i.p.) in male rats given levodopa (l‐DOPA, 50 mg kg−1, i.p.) and carbidopa ((−)‐l‐α‐methyl dopa, 50 mg kg−1, i.p.). In some studies pretreatment with pargyline (80 mg kg−1, i.p.) was used to block the function of monoamine oxidase (MAO).
Decreases of hypothalamic and striatal 3‐O‐methyl‐dopa (3‐OMD) levels were used as measures of the inhibition of peripheral COMT. The inhibition of brain COMT activity was estimated by decreases of hypothalamic and striatal homovanillic acid (HVA) and 3‐methoxytyramine (3‐MT; after pargyline) levels.
The three COMT inhibitors studied had different individual characteristics. OR‐611 was primarily a peripherally acting COMT inhibitor, decreasing 3‐OMD levels in the striatum (to 31–52%) and in the hypothalamus (to 16–27%) both in the control and pargyline‐treated animals at 1 and 3 h. It did not have any effect on brain HVA and 3‐MT.
Ro 40–7592 was a broad spectrum COMT inhibitor decreasing striatal and hypothalamic 3‐OMD (always to < 30%), HVA (to < 50%) and 3‐MT levels (to < 23%) significantly both at 1 and 3 h. It was more potent than OR‐611.
CGP 28014 functioned as a weak COMT inhibitor in the periphery inhibiting 3‐OMD formation only at 3 h. In contrast, it was fairly potent in decreasing the brain HVA and 3‐MT levels at 1 h (to 37–22% and 42–35% in the striatum, and to 57–33% and 64–35% in the hypothalamus, respectively) but not at 3 h. Since CGP 28014, unlike OR‐611 and Ro 40–7592, did not generally increase the brain DOPA, dopamine or DOPAC levels, it was not a typical COMT inhibitor.
Inhibitory effect of morphine on yawning induced by cholinoceptor and dopamine D2 receptor activation in rats
Authors: Zarrindast M.R. , Jamshidzadeh A. 
Published: July 2012

Bromocriptine (2, 4 and 8 mg kg−1, i.p.), physostigmine (0.05, 0.1 and 0.2 mg kg−1, i.p.) and pilocarpine (1, 3 and 5 mg kg−1, i.p.) induced dose‐dependent yawning in rats.
These responses were reduced in a dose‐dependent manner by pretreatment with morphine.
The inhibitory effect of morphine was reversed by naloxone.
Naloxone alone induced slight but significant yawning.
The present results suggest that morphine inhibits yawning in rats at an opiate receptor downstream from the sites at which cholinoceptor and dopamine D2 activation induce yawning. The anatomical location of these sites remains to be established.
Positive inotropic and negative chronotropic effects of (−)‐cis‐diltiazem in rat isolated atria
Authors: Nasa Yoshihisa , Ichihara Kazuo , Yoshida Rei , Abiko Yasushi 
Published: July 2012

The cardiovascular effects of (−)‐cis‐diltiazem, an optical isomer of diltiazem, were studied in the isolated atrium and aortic strip. (−)‐cis‐Diltiazem (30 μm or more) increased the developed tension of the rat left atrium, while (+)‐cis‐diltiazem (1 μm or more) decreased it.
(−)‐cis‐Diltiazem (1 to 100 μm) decreased the rate of spontaneous beating in the right atrium as did (+)‐cis‐diltiazem.
The potency of the positive inotropic action of (−)‐cis‐diltiazem was almost the same as that of ouabain in the rat left atrium, but in the guinea‐pig left atrium it was considerably weaker than that of ouabain.
In both endothelium‐intact and endothelium‐denuded aortic strips, (−)‐cis‐diltiazem relaxed the Ca2+‐induced contraction. In the endothelium‐intact rat aortic strip depolarized by 15 mm KCl, Bay K 8644, a calcium channel agonist, increased the contractile force, whereas (−)‐cis‐diltiazem did not.
These results indicate that (−)‐cis‐diltiazem has a positive inotropic action in isolated atria in rats and guinea‐pigs, but the mode of positive inotropic action of (−)‐cis‐diltiazem is different from that of ouabain or Bay K 8644.
Effects of lignocaine and quinidine on the persistent sodium current in rat ventricular myocytes
Authors: Ju Yue‐Kun , Saint David A. , Gage Peter W. 
Published: July 2012

The effects of the Class 1 antiarrhythmic agents lignocaine and quinidine on action potentials, and on sodium currents and potassium currents activated by depolarization, were examined in rat isolated ventricular myocytes by the whole cell, tight seal recording technique.
Tetrodotoxin and lignocaine shortened, whereas quinidine prolonged, the duration of the plateau phase of action potentials.
At low concentrations, lignocaine and quinidine blocked a persistent sodium current that was resistant to inactivation but they had only a small effect on the transient sodium current. At higher concentrations, they also blocked the transient sodium current.
Quinidine, but not tetrodotoxin or lignocaine, depressed potassium currents activated by depolarization and this could account for the prolongation of the plateau phase caused by quinidine.
It is suggested that block of the persistent sodium current may be responsible, at least in part, for the antiarrhythmic action of lignocaine and quinidine.
Effect of adenosine and adenosine analogues on cyclic AMP accumulation in cultured mesangial cells and isolated glomeruli of the rat
Authors: Olivera Ana , Lopez‐Novoa Jose M. 
Published: July 2012

Changes in intracellular levels of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) were studied in rat isolated glomeruli and cultured glomerular mesangial cells exposed to adenosine and to the preferential A1 receptor agonist N6‐R‐1‐methyl‐2‐phenylethyl adenosine (R‐PIA), or the potent A2 adenosine receptor agonist 5‐(N‐ethylcarboxamide)adenosine (NECA).
Whereas NECA and adenosine triggered a dose‐dependent increase in cyclic AMP values with EC50 values of approximately 10−6 m and 3 × 10−5 m respectively, R‐PIA lowered cyclic AMP levels at concentrations of 10−6 m or less and increased them at higher concentrations.
The time‐course of the increase induced by 10−6 m NECA was slower than that induced by 10−4 m adenosine. Adenosine produced a maximal stimulation within the first minute, whereas the effect of NECA in both glomeruli and mesangial cells was noticeable only from the second minute of incubation.
The effects of the agonists R‐PIA and NECA on the cyclic AMP system were blocked respectively by the A1 adenosine receptor antagonist, 8‐cyclopentyl‐1, 3‐dipropylxanthihe (DPCPX) at 10−6 m and the A2 antagonist N‐(2‐dimethylaminoethyl)‐N‐methyl‐4‐(2, 3, 6, 7‐tetrahydro‐2,b‐dioxo‐1, 3‐dipropyl‐1H‐purin‐8‐yl) benzene sulphonamide (PD115,199) at 10−6 m. Theophylline, a known antagonist of adenosine receptors, inhibited the action of adenosine on cyclic AMP in mesangial cells. Dipyridamole, an inhibitor of the uptake of adenosine by the cells, enhanced the response to adenosine.
These results suggest the existence of A1 and A2 adenosine receptors with opposite actions on intracellular levels of cyclic AMP in both glomeruli and mesangial cells. Adenosine seems to increase cyclic AMP through the activation of a surface adenosine receptor with pharmacological properties distinct from those exhibited by the A2 adenosine receptor.
Inhibition of noradrenaline release in the rat vena cava via prostanoid receptors of the EP3‐subtype
Authors: Molderings Gerhard , Malinowska Barbara , Schlicker Eberhard 
Published: July 2012

In segments of the rat vena cava preincubated with [3H]‐noradrenaline and superfused with physiological salt solution (containing desipramine and corticosterone), we studied the effects of prostaglandins of the D, E and F series, of a prostacyclin analogue and a thromboxane‐mimetic and of subtype‐selective prostaglandin E‐receptor (EP‐receptor) ligands on the electrically (0.66 Hz)‐evoked tritium overflow.
The electrically‐evoked tritium overflow was inhibited by prostaglandin E2 (maximum inhibition by about 80%; pIC40 7.49). The effect of prostaglandin E2 was not affected by rauwolscine, which, by itself, increased the evoked overflow; the α2‐adrenoceptor antagonist was added to the superfusion medium in all subsequent experiments. Indomethacin failed to affect either the evoked tritium overflow or its inhibition by prostaglandin E2.
The inhibitory effect of prostaglandin E2 on the electrically‐evoked tritium overflow was not altered by the EP1‐receptor antagonist, AH 6809 (6‐isopropoxy‐9‐oxoxanthene‐2‐carboxylic acid) at a concentration at least 30 fold higher than its pA2 value at EP1‐receptors. The following compounds mimicked the effect of prostaglandin E2 showing the following rank order of potencies: misoprostol (EP2‐/EP3‐receptor agonist) ≃ sulprostone (EP1/EP3‐receptor agonist) ≃ prostaglandin E1 = prostaglandin E2 ≫ iloprost (EP1‐/IP‐receptor agonist) = prostaglandin F2α. The evoked overflow was not affected by high concentrations of prostaglandin D2 or the thromboxane‐mimetic U46619 (9,11‐dideoxy‐11α, 9α‐epoxymethano‐prostaglandin F2α).
The present results suggest that the postganglionic sympathetic nerve fibres innervating the rat vena cava are endowed with presynaptic EP3‐receptors. They are not tonically activated by endogenously formed products of cyclo‐oxygenase and do not interact with the presynaptic α2‐adrenoceptors.
Nitric oxide synthase responsible for l‐arginine‐induced relaxation of rat aortic rings in vitro may be an inducible type
Authors: Moritoki Hideki , Takeuchi Shougo , Hisayama Tetsuhiro , Kondoh Wataru 
Published: July 2012

Characteristics of l‐arginine‐induced non‐endothelial nitric oxide (NO) formation in rat isolated thoracic aorta were investigated.
Relaxation to l‐arginine in arterial rings devoid of endothelium developed about 2 h after the first challenge with l‐arginine and reached a maximum after a further 4 h of incubation.
After the arteries had relaxed in response to l‐arginine, guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) production was stimulated. In fresh arteries that had not yet relaxed in response to l‐arginine, l‐arginine failed to elevate cyclic GMP levels.
Glucocorticoids, actinomycin D and polymyxin B prevented the development of l‐arginine‐induced relaxation and l‐arginine‐stimulated increase in cyclic GMP formation.
Once l‐arginine‐induced relaxation developed, these agents no longer suppressed the relaxation and increase in cyclic GMP formation to l‐arginine.6 From these results, it is suggested that in the isolated thoracic aorta of the rat, endotoxin in the medium triggers induction of a non‐endothelial NO synthase during prolonged incubation, which accelerates production of NO from added l‐arginine to cause relaxation of the arteries via cyclic GMP. Glucocorticoids and protein synthesis inhibitors may prevent induction of NO synthase. It is suggested that the NO synthase mediating the production of muscle‐derived NO from l‐arginine is an inducible type.
Activation of P1‐ and P2Y‐purinoceptors by ADP‐ribose in the guinea‐pig taenia coli, but not of P2X‐purinoceptors in the vas deferens
Authors: Hoyle Charles H.V. , Edwards Gareth A. 
Published: July 2012

The activity of adenosine 5′‐diphosphoribose (ADP‐ribose), a ribosylated purine nucleotide, was investigated on the carbachol‐contracted taenia coli, a tissue possessing P1‐ (A2) and P2Y‐purinoceptors and on the guinea‐pig vas deferens which possesses P2X‐purinoceptors.
In the vas deferens, where ATP (1 μm‐1 mm) produced concentration‐dependent contractions, ADP‐ribose was without effect at concentrations up to 1 mm.
In the taenia coli, ADP‐ribose (0.1 μm‐1 mm) produced concentration‐dependent relaxations with a potency similar to that of adenosine, but less than that of ATP. The pD2 values for ADP‐ribose, adenosine and ATP were 4.5 ± 0.07 (27), 4.4 ± 0.10 (9) and 5.5 ± 0.14 (21), respectively. The time‐course of the relaxations elicited by ADP‐ribose was found to be significantly longer than that for ATP and significantly shorter than that for adenosine.
The P1‐purinoceptor antagonist, 8‐phenyltheophylline (5 μm), produced parallel rightward shifts in the concentration‐response curves of the relaxations of the taenia coli elicited by ADP‐ribose and adenosine but not ATP.
Dipyridamole (0.3 μm), a purine nucleoside uptake inhibitor, potentiated the responses to adenosine and ADP‐ribose in the taenia coli. These potentiations were sensitive to 8‐phenyltheophylline (5 μm).6 Reactive blue 2, a P2Y‐purinoceptor antagonist, antagonized the inhibitory responses of ADP‐ribose and ATP in the taenia coli, without significantly altering the inhibitory responses of either adenosine or noradrenaline.7 In the presence of the potassium channel blocker, apamin (0.3 μm), the inhibitory responses of ADP‐ribose were severely attenuated, and the inhibitory responses of ATP in the taenia coli were converted to transient contractions. Further addition of 8‐PT blocked the residual responses of ADP‐ribose.8 The P2‐purinoceptor antagonist, suramin (500 μm), antagonized responses to ATP and ADP‐ribose, but not adenosine. Further addition of 8‐PT antagonized the residual responses to ADP‐ribose, but not to ATP.9 It is concluded that ADP‐ribose has a mixed pharmacological profile, evoking both P1 (A2)‐purinoceptor‐mediated responses and P2Y‐purinoceptor‐mediated responses, while being inert at P2X‐purinoceptors. It is suggested that ADP‐ribose may provide a useful starting point for the generation of structural analogues which have specific activity at the P2Y‐purinoceptor.
Tachykinin receptors in rabbit airways — characterization by functional, autoradiographic and binding studies
Authors: Black J.L. , Diment L.M. , Alouan L.A. , Johnson P.R.A. , Armour C.L. , Badgery‐Parker T. , Burcher E. 
Published: July 2012

In many species, both NK1 and NK2 tachykinin receptors appear to be important in mediating the contraction of airway smooth muscle. We have examined the distribution and characterization of receptors for tachykinins in rabbit airways using functional length tension studies, autoradiography and radioligand binding studies.
Contractile responses to tachykinins were elicited in four different areas of the respiratory tree — trachea, and three progressively more distal areas of the right bronchus. The NK2 receptor‐preferring agonists, neurokinin A (NKA), neuropeptide gamma (NPγ) and the NK2‐selective [Lys5 MeLeu9, Nle10]‐NKA(4–10) [NKA (4–10) analogue] produced similar contraction in all four areas. Substance P (SP) and the NK1‐selective [Sar9,Met(O2)11]‐SP (Sar‐SP) exhibited a marked location‐dependence in the magnitude of contraction, producing minimal contraction in the trachea and more proximal bronchi with contractions becoming progressively larger in the more distal airways. Senktide (which is selective for the NK3 receptor) produced negligible contraction in all areas.
The NK2‐selective antagonist, MDL29,913, was a weak antagonist of NKA and NKA(4–10) analogue. At a concentration of 2 μm, it produced a small but significant shift in the response curve to NKA and a greater shift (8 fold) in the curve to NKA(4–10) analogue, but it had no effect on responses to Sar‐SP. The non peptide NK, receptor antagonist, CP‐96,345, was also unexpectedly weak in this preparation. The pD2 value for Sar‐SP was decreased 27 fold by CP‐96,345 at a concentration of 1 μm, without alteration in the maximum response.
Autoradiographic binding sites to [125I]‐NKA were sparse over smooth muscle in proximal airway preparations and markedly increased in density in the more distal airways. There was negligible binding over vascular smooth muscle and epithelium.
Radioligand binding studies revealed binding to [125I]‐NKA which was 82% specific. The order of potency for inhibition of [125I]‐NKA binding was SP >= Sar‐SP > NKA = NPγ>CP‐96,345 > NKA (4–10) analogue > NKB ⋙ MEN 10207 (the NK2 subtype selective antagonist) > MDL 29,913 > senktide. This profile indicates binding predominantly to NK1 receptors.6 These results suggest that there are at least two types of tachykinin receptors in rabbit airways, a population of NK1 receptors, the density of which is greatest in the periphery and, in addition, NK2 receptors which are uniformly distributed throughout the airways. These receptors have unusual characteristics in that the NK1 antagonist, CP‐96,345 and the NK2 antagonist, MDL 29,913 respectively exhibited only weak potency.
Long‐term changes in gerbil brain neurotransmitter receptors following transient cerebral ischaemia
Authors: Araki Tsutomu , Kato Hiroyuki , Kogure Kyuya , Kanai Yasuo 
Published: July 2012

Receptor autoradiographic and histological techniques were used to investigate long‐term changes in the gerbil brain following transient cerebral ischaemia.
Transient ischaemia was induced for 3 min and 10 min, and the animals were allowed to survive for 8 months.
Histological examination revealed that 3 min ischaemia caused neuronal damage and mild shrinkage only in the hippocampal CA1 sector. Ten minutes of ischaemia produced severe neuronal damage in the striatum and the hippocampal CA1 and CA3 sectors. Considerable shrinkage was seen in the hippocampus; the dentate gyrus, however, was not damaged.
Three minutes of ischaemia produced changes in the binding of [3H]‐quinuclidinylbenzilate ([3H]‐QNB), [3H]‐muscimol, and [3H]‐MK‐801 in various brain regions, as determined autoradiographically. In contrast, [3H]‐cyclohexyladenosine ([3H]‐CHA) and [3H]‐PN200‐110 ([3H]‐isradipine) binding in the brain was unaltered.
Ten minutes of ischaemia resulted in a major loss of neurotransmitter receptors, especially in the hippocampus. The substantia nigra showed a significant reduction in [3H]‐CHA binding, whereas the striatum, which was morphologically damaged, showed no significant changes in any of the neurotransmitter receptors examined.6 The results demonstrated that long‐term survival after transient cerebral ischaemia produced alterations in neurotransmitter receptors, especially in the hippocampal formation, where considerable shrinkage was noted. These results also suggest that the hippocampal damage was not static, but progressive.
Effects of propofol and enflurane on action potentials, membrane currents and contraction of guinea‐pig isolated ventricular myocytes
Authors: Puttick R.M. , Terrar D.A. 
Published: July 2012

The effects of two general anaesthetics, propofol and enflurane, on electrical activity and contractions were investigated in single myocytes isolated from guinea‐pig ventricles.
Propofol and enflurane depressed the plateau and shortened the duration of action potentials.
Under voltage‐clamp conditions, propofol and enflurane reduced the amplitude of inward calcium current and of additional inward current activated by cytosolic calcium.
Contractions (measured with an optical technique) accompanying either action potentials or second inward currents (in response to depolarizations to 0 mV) were reduced by both anaesthetics. The mechanisms for calcium entry during contractions accompanying pulses to positive potentials such as + 60 mV are thought to differ from those accompanying second inward currents which are evoked by pulses from −40 to 0 mV. Enflurane enhanced the amplitudes of contractions accompanying pulses to positive potentials; in contrast these contractions were depressed by propofol.
In experiments where recovery processes were investigated by use of pairs of voltage‐clamp pulses with a variable interval between them, enflurane but not propofol slowed the recovery of contractions and calcium‐activated ‘tail’ currents. These observations are consistent with the hypothesis that enflurane may impair calcium handling by the sarcoplasmic reticulum whereas propofol has little, if any, effect at this site.6 In conclusion, the actions of propofol and enflurane on second inward currents contribute to their effects on action potentials and contraction. The negative inotropic effect of both anaesthetics may result partly from reduced calcium influx to trigger contraction, and for enflurane, partly from an impairment of calcium handling by the sarcoplasmic reticulum.