bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentiation of atrial natriuretic peptide‐stimulated cyclic guanosine monophosphate formation by glucocorticoids in cultured rat renal cells
Authors: Kanda K. , Ogawa K. , Miyamoto N. , Hatano T. , Seo H. , Matsui N. 
Published: July 2012

The effect of steroid hormones on atrial natriuretic peptide (ANP)‐stimulated cyclic guanosine monophosphate (cyclic GMP) formation was studied in cultured rat renal cells.
ANP increased cyclic GMP formation in a dose‐dependent manner, while cyclic AMP was not changed by ANP.
Steroid hormones did not affect basal cyclic GMP levels in cultured rat renal cells.
Dexamethasone at 10−8m increased ANP (human and rat ANP)‐stimulated cyclic GMP dose‐dependently in cultured rat renal cells. Cortisol, corticosterone and aldosterone at a concentration of 10−7m also potentiated ANP‐stimulated cyclic GMP formation, although triiodothyronine, oestradiol and testosterone were ineffective. Potentiation of ANP action by these steroids seems to parallel glucocorticoid activity.
Dexamethasone did not affect cyclic GMP formation stimulated by sodium nitroprusside which stimulates soluble guanylate cyclase in the cytosol. Therefore, the potentiating action of dexamethasone may be mediated through the action on particulate guanylate cyclase at the plasma membrane.
It is suggested that the diuretic action of glucocorticoids may, at least in part, be mediated through the potentiating effect of glucocorticoids on cyclic GMP response to ANP.
Castor oil increases intestinal formation of platelet‐activating factor and acid phosphatase release in the rat
Authors: Pinto A. , Calignano A. , Mascolo N. , Autore G. , Capasso F. 
Published: July 2012

When castor oil was administered by gavage to rats, the duodenum and jejunum but not ileum and colon produced large amounts (5–6 fold greater than control) of platelet activating factor (Paf).
Intraluminal release of acid phosphatase (AP) was also markedly increased (5–6 fold greater than control) in the duodenum and jejunum of castor oil‐treated rats and there was a correlation between the elevated release of AP and intestinal hyperaemia.
These findings support a role for Paf as a mediator of intestinal damage induced by castor oil.
EP 171: a high affinity thromboxane A2‐mimetic, the actions of which are slowly reversed by receptor blockade
Authors: Jones R.L. , Wilson N.H. , Lawrence Ruth A. 
Published: July 2012

Replacement of the four‐carbon ω‐terminus in 9,11‐endoxy‐10a‐homo prostaglandin H2 with a p‐fluorophenoxy group produces a compound (EP 171) with very high agonist potency at TP‐receptors.
On six isolated smooth muscle preparations EP 171 was 33–167 times more potent as a TP‐receptor agonist than U‐46619 (11,9‐epoxymethano PGH2); EC50 values ranged from 45 to 138 pm. The actions of EP 171 were difficult to study because of their slow onset and offset. For example, on the guinea‐pig trachea the time required for 50% reversal of EP 171‐induced contractions during washout was about 3 h.
On the pig pulmonary artery, a more rapidly responding preparation, it was possible to show that the TP‐receptor antagonist EP 092 blocked the contractile actions of EP 171 and U‐46619 to similar extents: pA2 = 8.09 and 8.15 respectively.
EP 171 was also a very potent activator of human blood platelets, being about 90 times more potent than U‐46619. Both shape change (0.1 nm) and aggregation (1 nm) were slow in onset, a profile not previously observed for a thromboxane A2‐mimetic.
When potencies at TP‐, EP1‐(guinea‐pig fundus) and FP‐(dog iris sphincter) receptors were compared, EP 171 showed a higher specificity as a TP‐receptor agonist than either STA2 or U‐46619. These studies also showed that contrary to earlier reports, the guinea‐pig fundus does contain TP‐receptors mediating muscle contraction. However, the maximal response due to activation of TP‐receptors was only about 35% of the PGE2 maximum.
Established responses to EP 171 were slowly reversed following addition of a high concentration of a TP‐receptor antagonist (EP 092, GR 32191 or BM 13177). Faster reversals of three less potent 16‐p‐halophenoxy prostanoids and U‐46619 were obtained. Half‐times for offset (and onset) of agonist action appeared to correlate with potency rather than with lipophilicity.
Competition between the agonists and a radio iodinated PTA2 derivative ([125I]‐PTA‐OH) for binding to TP‐receptors on intact human platelets was studied. IC50 values correlated well with aggregating potency, EP 171 having the lowest IC50 of 2.9 nm. The true Ki for EP 171 may be about 1 nm if both its racemic nature and reduction of initial free ligand concentration due to TP‐receptor binding are taken into account.
It is concluded from a comparison of agonist potency rankings that subclassification of the TP‐receptor is not warranted at this time. The factors that may be responsible for the slow kinetics of EP 171 action are discussed.
Arterial catecholamine levels in morphine‐treated rats subjected to sympathetic nerve stimulation
Authors: Leung Christopher M.K. , Dai Soter , Ogle Clive W. 
Published: July 2012

The effect of acute or chronic morphine treatment on the changes in arterial noradrenaline and adrenaline levels in response to sympathetic nerve stimulation was studied in rats.
Rats which had been chronically treated with morphine in their drinking fluid for 21 days were shown to be morphine‐tolerant, as revealed by the tail‐immersion test for analgesia.
It was found that animals given either acute or chronic morphine treatment had similar basal concentrations of arterial catecholamines to their controls.
Sympathetic nerve stimulation produced significant increases in arterial noradrenaline and adrenaline levels in both the control and morphine‐treated animals. However, the degree of arterial noradrenaline elevation was significantly less in morphine‐tolerant animals.
This phenomenon was not observed in acutely morphine‐treated rats or at 2 weeks following opiate withdrawal in animals which had been treated previously with morphine for 3 weeks.
The findings suggest that chronic morphine treatment in rats not only leads to opiate tolerance but also reduces catecholamine release in response to sympathetic nerve stimulation.
Agonist‐induced glycogenolysis in rabbit retinal slices and cultures
Authors: Ghazi Hani , Osborne Neville N. 
Published: July 2012

The effects of different putative retinal transmitters and/or modulators on glycogenolysis in rabbit retinal slices and in retinal Müller cell cultures were examined.
Incubation of rabbit retinal slices or primary retinal cultures (either 3–5 day‐old or 25–30 day‐old) in a buffer solution containing [3H]‐glucose resulted in the accumulation of newly synthesized [3H]‐glycogen.
Noradrenaline (NA), isoprenaline, vasoactive intestinal peptide (VIP), 5‐hydroxytryptamine (5‐HT) and 8‐hydroxy‐dipropylaminetetralin (8‐OH‐DPAT) stimulated the hydrolysis of this newly formed 3H‐polymer. The potency order of maximal stimulations was: VIP > NA > isoprenaline > 5‐HT > 8‐OH‐DPAT.
The putative retinal transmitters, dopamine, γ‐aminobutyric acid (GABA), glycine and taurine and the muscarinic agonist carbachol (CCh) had no effect on [3H]‐glycogen content.
The glycogenolytic effects of NA/isoprenaline and 5‐HT/8‐OH‐DPAT appear to be mediated by β‐adrenoceptors and 5‐HT1 receptors (possibly 5‐HT1A), respectively while the VIP‐induced response involved another receptor subtype.
Agonists which mediated [3H]‐glycogen hydrolysis also stimulated an increase in adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) formation. Both responses are blocked to a similar extent by the same antagonists and so are probably mediated via the same receptor subtypes. Moreover, dibutyryl cyclic AMP (db cyclic AMP) promoted tritiated glycogen breakdown in the three retinal preparations.
Not all receptors linked to cyclic AMP production however promote glycogenolysis. Dopamine and apomorphine stimulated cyclic AMP formation via D1‐receptors without influencing glycogenolysis. These receptors are exclusively associated with neurones.
Kinins act on B1 or B2 receptors to release conjointly endothelium‐derived relaxing factor and prostacyclin from bovine aortic endothelial cells
Authors: D'Orléans‐Juste Pedro , de Nucci Gilberto , Vane John R. 
Published: July 2012

Bradykinin (Bk) induced the coupled release of endothelium‐derived relaxing factor (EDRF) and prostacyclin (PGI2) from bovine aortic endothelial cells grown in culture. The B2 kinin receptor antagonist, [d‐ArgO,Hyp3,Thi5,8,d‐Phe7]‐Bk, abolished this release by Bk.
Des‐Arg9‐Bk, a B1 kinin receptor agonist, also induced the release of EDRF and PGI2, but much higher concentrations were required to obtain a similar release to that induced by Bk.
[Leu8],des‐Arg9‐Bk, a B1 receptor antagonist, significantly reduced the response to des‐Arg9‐Bk without affecting the release induced by Bk.
The release of EDRF and PGI2 induced by arachidonic acid or ADP was not significantly affected by the B2 or the B1 antagonist.
We conclude, therefore, that Bk and des‐Arg9‐Bk were acting respectively on B2 and B1 bradykinin receptors.
The possible role of kinin receptors in the release of EDRF and PGI2 from endothelial cells is discussed.
The effects of calcium antagonists on calcium overload contractures in embryonic chick myocytes induced by ouabain and veratrine
Authors: Patmore Leslie , Duncan Greig P. , Spedding Michael 
Published: July 2012

The protective effects of some calcium antagonists against different forms of calcium overload contracture were investigated in embryonic chick cardiac myocytes.
Tetrodotoxin‐sensitive sodium currents were recorded from the myocytes by the whole‐cell voltage‐clamp technique. Although the peak current was attenuated by veratrine, the inactivation process was markedly inhibited, resulting in a large increase in the total inward current. Action potentials were prolonged by veratrine, automaticity was inhibited and the membrane potential depolarized from −79 to around −45 mV.
Measurements of contraction were made from aggregates of myocytes using a video edge detection technique which quantified edge movement. Veratrine caused an initial positive inotropism then inhibited automaticity of aggregates with subsequent development of a tonic contracture to around 300% of the twitch contraction.
Veratrine‐induced contractures were not significantly affected by 10 μm diltiazem or verapamil. Nifedipine (5 μm), nimodipine (5 μm) and ryanodine (5 μm) also had little effect whilst nicardipine and flunarizine caused a concentration‐dependent inhibition of veratrine‐induced contractures with IC50 s of 3 μm and 2 μm respectively.
Veratrine‐induced contractures were found to be very sensitive to extracellular calcium concentration with an EC50 of 32 μm. Edge movement associated with beating of the myocytes was much less sensitive to calcium (EC50 = 1 mm). Submaximal veratrine contractures in 20–50 μm extracellular calcium were not potentiated by 1 μm Bay K 8644.
Tetrodotoxin also inhibited veratrine‐induced contractures but did not affect contractions induced by ouabain in the presence of 10 μm diltiazem.
Ouabain‐induced contractures were also inhibited by nicardipine and flunarizine indicating that these drugs can protect against calcium overload in embryonic chick heart by a mechanism independent of the normal form of voltage‐sensitive sodium or calcium channels.
GABAA receptor‐mediated positive inotropism in guinea‐pig isolated left atria: evidence for the involvement of capsaicin‐sensitive nerves
Authors: Maggi Carlo Alberto , Giuliani Sandro , Manzini Stefano , Meli Alberto 
Published: July 2012

Isolated left atria from reserpine‐pretreated guinea‐pigs, electrically driven (3 Hz) in the presence of atropine (1 μm), phentolamine (0.3 μm) and propranolol (1 μm), responded to a train of stimuli (10 Hz for 2.5 s) with a delayed neurogenic positive inotropic response which was insensitive to hexamethonium (10 μm) but abolished by either tetrodotoxin (1 μm), ω‐conotoxin (0.1 μm), in vitro capsaicin desensitization or desensitization to calcitonin gene‐related peptide (CGRP).
In these experimental conditions, γ‐aminobutyric acid (GABA) produced a concentration‐related (10 μm‐1 mm) positive inotropic response similar to that produced by electrical field stimulation. The effect of GABA was competitively antagonized by bicuculline methiodide (10 μm), a GABAA receptor antagonist.
The selective GABAA receptor agonists, muscimol and homotaurine mimicked the positive inotropic effect of GABA while baclofen, the selective GABAB receptor agonist, did not.
The action of GABA (1 mm) was abolished by either tetrodotoxin (1 μm), ω‐conotoxin (0.1 μm), in vitro capsaicin desensitization or desensitization to CGRP, while it was unaffected by hexamethonium. In contrast, the inotropic response to CGRP was unaffected by tetrodotoxin, ω‐conotoxin, bicuculline methiodide, hexamethonium or in vitro capsaicin desensitization, but was abolished by CGRP desensitization.
In the spontaneously beating guinea‐pig right atrium, GABA (1 μm) produced a small and transient positive chronotropic effect that was no longer observed after in vitro desensitization with capsaicin (1 μm).
In the guinea‐pig isolated perfused heart from reserpine‐pretreated animals (with atropine, phentolamine and propranolol in the perfusion medium), GABA (1 μm) produced a transient tachycardia and a small increase in coronary flow. Both capsaicin (1 μm) and CGRP (1 μm) produced marked tachycardias and increases in coronary flow. After exposure to capsaicin (1 μm), no effect of GABA could be detected.
We conclude that, in the guinea‐pig heart, GABAA receptors, presumably located on the preterminal region of capsaicin‐sensitive sensory nerves, initiate a conducted impulse (since it is tetrodotoxin‐sensitive) which leads to transmitter release (endogenous CGRP‐like material) by activation of ω‐conotoxin‐sensitive, voltage‐sensitive calcium channels and a functional response.
Contraction of the rat isolated aorta caused by Clostridium perfringens alpha toxin (phospholipase C): evidence for the involvement of arachidonic acid metabolism
Authors: Fujii Yoshio , Sakurai Jun 
Published: July 2012

Alpha toxin produced by Clostridium perfringens contracted the rat isolated aorta and stimulated release of arachidonic acid in the tissue.
Quinacrine did not inhibit contraction caused by the toxin.
Indomethacin blocked contraction caused by the toxin in a dose‐dependent manner and markedly increased levels of arachidonic acid released by the toxin.
The toxin‐induced contraction was blocked by the thromboxane synthetase inhibitor OKY‐046 and the thromboxane A2 (TXA2) antagonist ONO‐3708.
The toxin stimulated production of TXB2 and this was blocked by pretreatment with either indomethacin or OKY‐046.
Toxin‐induced contraction was diminished by pretreating aorta with collagenase or by rubbing the intimal surface to remove the endothelium.
These data suggest that the contractile response to the toxin is associated with stimulation of TXA2 production from arachidonic acid released by the toxin in the endothelial cells of the aorta.
Regional haemodynamic effects of vasopressin infusion in conscious, unrestrained, Brattleboro rats
Authors: Gardiner S.M. , Compton A.M. , Bennett T. 
Published: July 2012

Incremental rates of infusion (0.027–4.0 pmol min−1) of exogenous vasopressin were given for 10 min periods to conscious, Brattleboro (i.e. vasopressin‐deficient) rats, which had been chronically instrumented with pulsed Doppler probes and intravascular catheters (to permit assessment of regional haemodynamic changes).
There were no significant effects of the two lowest rates of infusion (0.027 and 0.105 pmol min−1) but, after 10 min of vasopressin infusion at 0.313 pmol min−1, superior mesenteric vasoconstriction had occurred unaccompanied by any other changes. Infusion of vasopressin at 0.687 pmol min−1 produced increases in blood pressure and in both mesenteric and hindquarters vascular resistance, but no change in renal vascular resistance or heart rate. These results do not indicate specific interactions between exogenous vasopressin and baroreflex mechanisms to offset the pressor effect of the neuropeptide.
The marked bradycardia, hypertension and renal, mesenteric and hindquarters vasoconstriction seen after 10 min infusion of vasopressin at 4.0 pmol min−1 were all abolished 10 min after administration of an antagonist of V1‐receptors ((+)−(CH2)5Tyr(Et)DAVP); additional antagonism of V2‐receptors (with the non‐selective antagonist (+)−(CH2)5Tyr(Et)VAVP) had no effects on any measured variable. Hence, the present experiments provide no evidence for important vasodilator effects of vasopressin in conscious, Brattleboro rats.
An in vivo dialysis and behavioural study of the release of 5‐HT by p‐chloroamphetamine in reserpine‐treated rats
Authors: Adell A. , Sarna G.S. , Hutson P.H. , Curzon G. 
Published: July 2012

Reserpine (2.5 mg kg−1 i.p.) decreased rat brain 5‐hydroxytryptamine (5‐HT) by 86% 24 h later but most components of the 5‐HT‐dependent behavioural syndrome induced by p‐chloroamphetamine (PCA, 5 mg kg−1 i.p.) or 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeODMT, 5 mg kg−1 i.p.) over 1 h after administration were unaffected. However, Straub tail was increased after giving PCA or 5‐MeODMT and head weaving was decreased after giving 5‐MeODMT.
Frontal cortex extracellular 5‐HT concentrations of vehicle pretreated rats before injection of PCA, as calculated from dialysate 5‐HT concentrations, were about 1/1000th of corresponding brain values. Extracellular 5‐hydroxyindoleacetic acid (5‐HIAA) and brain values were comparable with each other. Dialysate 5‐HT increased after PCA with peak values at 20–40 min.
Reserpine pretreatment reduced dialysate 5‐HT concentration before PCA was given but the net increase (AUC) over the 1 h after PCA did not differ significantly from that seen in animals pretreated with vehicle. Dialysate 5‐HIAA values slowly decreased after PCA injection in both reserpine and vehicle pretreated groups.
The results suggest that PCA causes the 5‐HT syndrome by releasing 5‐HT from the neuronal cytoplasm but that physiological release of 5‐HT occurs from vesicular stores.
5‐HT3 receptor antagonists injected into the area postrema inhibit cisplatin‐induced emesis in the ferret
Authors: Higgins G.A. , Kilpatrick G.J. , Bunce K.T. , Jones B.J. , Tyers M.B. 
Published: July 2012

The purpose of the present study was to identify and investigate the role of 5‐hydroxytryptamine3 (5‐HT3) receptors in the area postrema in the control of cisplatin‐induced emesis in the ferret.
Homogenate binding and autoradiography experiments using the high affinity 5‐HT3 receptor ligand, [3H]‐GR65630, identified the presence of a high concentration of 5‐HT3 receptors in the area postrema of the ferret.
Intraperitoneal injection of the 5‐HT3 receptor antagonists, GR38032F, GR65630A and MDL72222, at doses of 1, 0.1 and 1 mg kg−1 respectively, inhibited emesis induced by cisplatin, 9 mg kg−1 i.p.
Discrete injection of low doses of the 5‐HT3 receptor antagonists directly into the area postrema region also inhibited cisplatin‐induced (9 mg kg−1 i.p.) emesis. The dose ranges used were: GR38032F, 0.01–1 μg; GR65630A, 0.001–0.1 μg; MDL72222, 0.1–10 μg.
Cisplatin‐induced emesis was not inhibited by discrete injection of ketanserin (30 μg) or methiothepin (30 μg) into the area postrema. Injection of the 5‐HT3 receptor agonist, 2‐methyl‐5‐HT, directly into the area postrema produced an incomplete emetic response.
These results confirm a role of 5‐HT, and in particular 5‐HT3 receptors, in the control of cisplatin‐induced emesis, and show that at least one functional site for these receptors in modulating the emetic response is the area postrema, the locus of the chemoreceptor trigger zone.
(+)−[3H]‐PN 200–110 binding to cell membranes and intact strips of portal vein smooth muscle: characterization and modulation by membrane potential and divalent cations
Authors: Dacquet C. , Loirand G. , Rakotoarisoa L. , Mironneau C. , Mironneau J. 
Published: July 2012

Specific binding of the calcium‐antagonist dihydropyridine derivative, (+)−[3H]‐PN 200–110 (isradipine), to cell membranes of equine portal vein smooth muscle was compared with binding to intact strips isolated from rat portal veins.
Specific binding to vascular smooth muscle membranes was of high affinity, saturable and reversible. The dissociation constant obtained from association and dissociation kinetics of (+)−[3H]‐PN 200–110 was similar to that obtained from equilibrium binding and competition experiments.
Specific binding of (+)−[3H]‐PN 200–110 was completely displaced by unlabelled dihydropyridines. Among other calcium antagonists, D888 and (+)−cis‐diltiazem partially inhibited the binding at 25°C. At 37°C, only (+)−cis‐diltiazem stimulated the binding. LaCl3, CdCl2, NiCl2, CoCl2 had inhibitory effects, whereas KCl and NaCl had no effect.
When intact strips of portal vein were incubated in high external potassium concentrations for 30 min, the Kd was lowered to 0.04 ± 0.01 nm from the control value of 0.14 + 0.02 nm (n = 5), thereby indicating that (+)−[3H]‐PN 200–110 bound to voltage‐dependent calcium channels, with a higher affinity, in the depolarized state.
When external Ca2+ was removed or substituted with Ba2+ or Sr2+, Kd values increased suggesting that the dihydropyridine binding to intact strips was modulated by binding of Ca2+ ions to voltage‐dependent calcium channels.
An investigation into the mechanisms of inhibition of calcium channel currents in cultured sensory neurones of the rat by guanine nucleotide analogues and (−)− baclofen
Authors: Dolphin A.C. , McGuirk S.M. , Scott R.H. 
Published: July 2012

The mechanism of inhibition of calcium channel currents by the guanine nucleotide analogue guanosine 5′‐O‐3 thiotriphosphate (GTP‐γ‐S) and by the GABAB agonist (−)‐baclofen has been studied in cultured dorsal root ganglion neurones of the rat. The inhibition by GTP‐γ‐S is particularly characterized by an abolition of the transient component of calcium channel currents carried either by Ba2+ (IBa) or by Ca2+ (ICa).
The effect of agents increasing intracellular cyclic AMP levels has been examined. Neither internal cyclic AMP nor forskolin prevented the inhibition of IBa by baclofen. Neither forskolin nor pretreatment of cells with cholera toxin prevented the inhibition of the transient component of IBa by GTP‐γ‐S. However, both these treatments increased the amplitude of the sustained IBa in the presence of GTP‐γ‐S. The ATP analogue adenosine imido‐diphosphate which inhibits many ATP requiring enzymes did not prevent the effect of GTP‐γ‐S although it reduced the amplitude of IBa.
Baclofen (100 μm) produced a 22 ± 2% increase in inositol phosphate production in 30 s, whereas the increase produced by bradykinin (1 μm) was 70 + 14%. However, unlike baclofen, bradykinin did not inhibit IBa or ICa in these cells.
The effect of protein kinase C inhibitors was examined. Polymixin B (20 μm in patch pipette) had no effect on the inhibition of IBa by baclofen or GTP‐γ‐S. A higher concentration (100 μm) alone inhibited IBa and no further inhibition by baclofen was observed. Neither H7 (50 μm) nor staurosporine (100 nm), applied extracellularly, prevented the response to GTP‐γ‐S.
The protein kinase C activator di‐octanoyl glycerol (20 μm) did not inhibit IBa. Arachidonic acid (100 μm) also produced no inhibition of IBa.
In conclusion we have obtained no evidence that a second messenger system mediates the inhibition of calcium channel currents by GTP‐γ‐S or baclofen in dorsal root ganglion neurones. These results support the hypothesis that GABAB receptors are directly coupled to calcium channels by G proteins.