bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of Different Receptors in the Central and Peripheral Effects of Histamine on Intestinal Motility in the Rat
Authors: Fargeas M J , Fioramonti J , Bueno L 
Published: April 2011

Abstract
The effects of histamine on intestinal motility have been investigated in conscious rats, fed or fasted, using an electromyographic method. Histamine peripherally administered (10 mg kg−1) in 15 h fasted rats induced an inhibition followed by a period of irregular spiking activity disrupting the duodenojejunal migrating myoelectric complexes (MMC) and suppressed the postprandial motor spiking activity when administered 50 min after a meal. The selective agonist of the H1receptors, 2-pyridylethylamine (2-PEA) induced an irregular spiking activity while dimaprit acting on H2-receptors, inhibited the MMC pattern. Effects of peripherally administered histamine were antagonized by previous administration of chlorpheniramine (0·5 mg kg−1 i.p.) and in a lesser extent by Cimetidine (10 mg kg−1 i.p.). Histamine (1–10 μg) administered intracerebroventricularly (i.c.v.) in fasted rats increased the motor cycle frequency and immediately restored the MMC pattern when given to fed rats. Among the three agonists of the H1-H2- and H3-receptors (2-PEA, dimaprit and R-α-methylhistamine, respectively) only R-α-methylhistamine (1–10 μg i.c.v.) was able to reproduce this effect. It is concluded that the effects of histamine on intestinal motility were centrally and peripherally mediated involving mainly Hi-receptors at the peripheral level and H3-receptors at the CNS level.
Effect of centrally administered prostaglandin D2 and some prostaglandin synthesis inhibitors on carrageenan-induced paw oedema in rats
Authors: Bhattacharya S K , Rao P J R Mohan , Gupta G Das 
Published: April 2011

Abstract
The putative modulatory role of central prostaglandins (PGs) on peripheral inflammation has been explored by investigating the effects of intracerebroventricularly (i.c.v.) administered PGD2, the major rodent brain PG, hydrocortisone, a phospholipase A2 inhibitor, and the cyclo-oxygenase inhibitors, paracetamol and mefenamic acid, on carrageenan-induced paw inflammation in rats. PGD2 produced a dose-related inflammation-augmenting effect, whereas hydrocortisone and the PG synthesis inhibitors, paracetamol and mefenamic acid, induced attenuation of the peripheral oedema. These findings confirm an earlier report from this laboratory which had indicated that central PGs may modulate peripheral inflammation and that conventional anti-inflammatory agents exert at least part of their effect by inhibiting central PG synthesis.
The effect of varying extents of Fluosol-DA or normal saline haemodilution on the dose dependent kinetics of phenytoin in the rat
Authors: Shrewsbury Robert P , Oliver Sharon R , Lewis Lee M , Anderson Wanda T , White Lisa G 
Published: April 2011

Abstract
Phenytoin kinetics were determined in rats in which the blood was moderately haemodiluted with 20 or 40 mL kg−1 of Fluosol-DA or normal saline. Rats received one of three intravenous phenytoin doses (10, 40, 50 mg kg−1) 0·5, 24, 48, or 72 h after haemodilution and were compared with non-exchanged controls. Haemodilution with either 20 or 40 mL kg−1 of Fluosol or saline had no influence on the dose-dependent kinetics of phenytoin. Haemodilution with 40 mL kg−1 of Fluosol decreased the half-life of phenytoin’s major metabolite, HPPH, after a 50 mg kg−1 dose. Neither Fluosol nor saline haemodilution affected the normal delay in biliary cycling of HPPH.
Solubilities of Adenosine Antagonists Determined by Radioreceptor Assay
Authors: Bruns R F , Fergus J H 
Published: April 2011

Abstract
The practical use of many adenosine receptor antagonists is limited by poor aqueous solubility. In some cases, solubilities are so low that they are difficult to measure by conventional means. To determine solubilities of adenosine antagonists, a sensitive radioreceptor method has been developed. Solubilities in Tris buffer (pH 7·7) ranged from 141 nM for 8−(2−amino−4−hlorophenyl)−1,3−dipropylxanthine to 945 μM for the amino-substituted xanthine PD 113,297. Ratios between solubility and adenosine receptor affinity varied from 15·8 for the A2-selective antagonist HTQZ to 169 000 for PD 113,297. From literature data on functional activity, it is apparent that useful adenosine antagonist activity in-vivo is only seen in compounds with solubility/affinity ratios greater than 100.
Pipequaline Transport from Blood to Brain and Liver: Role of Plasma Protein-bound Drug
Authors: Essassi Dalila , Urien Saik , Zini Roland , Tillement Jean-Paul 
Published: April 2011

Abstract
Brain uptake of pipequaline (45319 RP) has been studied in-vivo after a single capillary transit by intracarotid injection to rats. Pipequaline is extensively bound to plasma proteins: i.e. human serum albumin (HSA), α1-acid glycoprotein (AAG), lipoproteins and blood cells, mainly erythrocytes. The dialysable drug fraction as measured in-vitro by equilibrium dialysis at 37°C, was inversely related to the concentration of binding component. Similarly, the brain uptake of pipequaline was inversely related to the protein concentration of the injected solution. However, the measured brain uptake of pipequaline was higher than those predicted by in-vitro measurements of dialysable drug for all proteins and erythrocytes, except HSA. These results show that a fraction of bound pipequaline as measured in-vitro is available for transport through the blood brain barrier. HSA-bound pipequaline is an exception as it is restricted to the vascular space. Pipequaline was totally cleared by the liver through a single passage.
Influence of Dopaminergic and Noradrenergic Systems on the Release of Opioid Peptides in Guinea-pig Ileum
Authors: Milanés M Victoria , Martínez J Antonio , Vargas M Luisa 
Published: April 2011

Abstract
Neuroleptic drugs increase the biosynthesis and release of opioid peptides from the myenteric plexus of guinea-pig ileum. In the present work, the involvement of dopamine receptors or α-adrenoceptors in the release of opioids from the myenteric plexus of guinea-pig was investigated. Acute or chronic treatment with prazosin, an α1-blocking drug, produced no changes in the release of these peptides. Release was also unchanged after acute or chronic treatment with the α2-blocking drug yohimbine. However, treatment with domperidone, a selective dopamine receptor antagonist, resulted in an increase in the release of opioids, as did treatment with (-)−3−(3−hydroxyphenyl)-N-n-propylpiperidine ((-)−3−PPP), a dopamine autoreceptor stimulant. It is concluded that the effect of neuroleptics on the release of opioids from myenteric plexus is due to the blockade of dopamine receptors, and that interruption of dopaminergic transmission produces an increase in opioid release at this level.
Putrescine reverses aconitine-induced arrhythmia in rats
Authors: Bazzani Carla , Genedani Susanna , Tagliavini Simonetta , Bertolini A 
Published: April 2011

Abstract
Putrescine, (150–300 mg kg−1 i.v.) injected into anaesthetized rats reversed aconitine-induced arrhythmia and restored sinus rhythm. In the same experimental model, quinidine and lignocaine had a transient therapeutic effect, procainamide was practically ineffective and verapamil worsened the aconitine arrhythmia, causing the death of all treated animals. These data demonstrate that putrescine has an antiarrhythmic effect in an experimental model particularly resistant to usual antiarrhythmic treatments.
Moisture Sorption Profiles and Tensile Strength of Tableted Phenobarbitone Formulations
Authors: Malamataris S , Dimitriou A 
Published: April 2011

Abstract
The tensile strength of tablets made from phenobarbitone and sodium phenobarbitone formulations after storage at increasing ambient relative humidity has been investigated. The moisture sorption and desorption profiles of the formulations were analysed for three locations of moisture: monolayer adsorbed moisture, normally condensed moisture and absorbed moisture. Maxima in tensile strength occur at moisture distributions determined by the disintegrant used. The changes in tensile strength have been explained in terms of changes produced in the interparticle separation, the range of the interparticle forces and changes in the ratio of the binding to diffusional forces, acting on the water molecules which are on the particles' surface.
Comparative Drug Exsorption in the Perfused Rat Intestine
Authors: Huang Jin-Ding 
Published: April 2011

Abstract
The factors affecting drug exsorption into the gastrointestinal tract are uncertain. In this study, the intestinal clearance (CLi) of compounds which vary in their lipophilicity, serum protein binding, molecular weight and ionic charge at physiological pH, has been measured. Male Sprague-Dawley rats with ligated bile ducts were infused with the test compounds through the jugular vein. The small intestine was intubated and perfused with Tyrode solution at 20 mL h−1. The CLi of the compounds investigated (urea, polyethylene glycol, inulin, albumin, dextran, barbituric acid, salicylic acid, thiobarbital, thiopental, thioseconal, theophylline, S-disopyramide and quinidine) was determined under anaesthesia by dividing the rate of a component's appearance rate in the perfusate by its carotid arterial concentration. Serum protein binding of the compounds was determined by equilibrium dialysis. The n-octanol-water partition coefficients of the compounds were measured as indices of lipophilicity. The CLi values of dextran, albumin, inulin, polyethylene glycol and urea were 0.56, 1.03, 4.5, 4.8 and 12.0 mL h−1, respectively. The larger the molecular weight of a compound, the smaller its CLi. The molecular weight is apparently one of the major determinants of CLi. Thiobarbital, thiopental and thioseconal are compounds of similar structure with increasing lipophilicity and serum protein binding. The CLi of thiobarbital, thiopental and thioseconal was proportional to the unbound fraction in serum. The unbound clearance (CLui) of three thiobarbiturates were similar (∼ 11 mL h−1). The unbound fraction of drug in serum appears to be a factor determining their CLi. Barbituric acid and salicylic acid, two acidic compounds, showed a low CLi (&lt; 1 mL h−1). In contrast with barbituric acid and salicylic acid, the CLi of theophylline, S-disopyramide and quinidine was much higher (&gt; 30 mL h−1). The CLi of dextran, thiopental or S-disopyramide was not affected by altered perfusion rate. Other than molecular weight and serum protein binding, the ionic charge of compounds at physiological pH was the most significant factor affecting CLi. The lipophilicity of compounds and the perfusion rate did not seem to be important factors.
Modulation of the GABAA Receptor by Barbiturates and Pregnane Steroids: Differential Effects of the Influence of Assay Temperature
Authors: Yau J L W , Balfour D J K , Stevenson I H 
Published: April 2011

Abstract
The effect of temperature on the modulation of the GABAA receptor by barbiturates and steroids has been investigated in-vitro using a radioreceptor binding assay. Displaceable [3H]muscimol binding to a crude membrane preparation from rat cerebral cortex was enhanced by the endogenous steroid metabolite, 5β-pregnan-3α-ol-20-one, by the synthetic steroid, alphaxalone, and by pentobarbitone in a dose-dependent manner. Hydrocortisone and corticosterone had no significant effect on [3H]muscimol binding. Analysis of binding data using a curve-fitting program (‘Ligand’) showed that both pentobarbitone (1 mM) and 5β-pregnan-3α-ol-20-one (10 μM) increased the apparent number of high affinity binding sites in the membrane but had no effect on the affinity of [3H]muscimol binding (Kd approx. 11 nM). Increasing the assay temperature from 0°C to 35°C decreased [3H]muscimol binding and decreased the enhancement of binding by pentobarbitone but had no effect on 5β-pregnan-3α-ol-20-one enhancement of binding. 5α-Pregnan-3α-ol-20-one increased the apparent rate of association of [3H]muscimol binding to its receptor whereas pentobarbitone had no effect. These different effects on the apparent association rate and the different responses to temperature, suggest that the barbiturate and steroid may interact with the GABAA receptor through different binding sites.
Characterization of cysteinyl-leukotriene formation in primary astroglial cell cultures
Authors: Seregi András , Simmet Thomas , Schobert Angelika , Hertting Georg 
Published: April 2011

Abstract
The formation and composition of cysteinyl-leukotrienes (LT) in primary astroglial cell cultures prepared from newborn rat brain has been studied. Small amounts of cysteinyl-LT determined in terms of LTC4-like material in the supernatants of the cultures, became detectable after stimulation of the cells with 10−5 M ionophore A23187. Cysteinyl-LT formation increased with time, reaching about 600 pg (mg protein)−1 after 60 min incubation. In contrast, considerable thromboxane (TX) B2 synthesis was found at 5 min following A23187-stimulation (about 30 ng TXB2 (mg protein)−1). The synthesis of cysteinyl-LT was abolished by 5 × 10−5 M nordihydroguaiaretic acid (NDGA). Irrespective of the duration of incubation, blockage of prostanoid synthesis by 10−6 M indomethacin did not result in increased cysteinyl-LT production. Reversed phase HPLC combined with radioimmunological detection showed that, after 60 min incubation in the presence of A23187, LTC4 and LTD4 accounted for practically all the LTC4-like immunoreactive material in the supernatants of cell cultures. No significant amounts of LTE4 could be detected. The results show that astrocytes may contribute to brain LTC4 and LTD4 synthesis. However, the cellular site of cerebral LTE4 formation seems to be other than the astroglia.
Glycyrrhetinic acid derivatives: Anti-nociceptive activity of deoxoglycyrrhetol dihemiphthalate and the related compounds
Authors: Inoue Hideo , Kurosu Shinobu , Takeuchi Tadao , Mori Takeo , Shibata Shoji 
Published: April 2011

Abstract
The possible inhibitory effect of deoxoglycyrrhetol dihemiphthalate (I) and the related compounds (18β-olean-9(11), 12-diene-3β,30-diol) (II) and (olean-11,13(18)-diene-3β,30-diol) III derived from glycyrrhetinic acid has been examined on acetic acid-induced writhing in mice. The compounds inhibited writhing dose-dependently. Their ED50 values were 14,31 and 22 mg kg−1 for I, II, and III, respectively. The compounds like aspirin, also significantly suppressed PGE2 production in peritoneal fluid together with the writhing response. The results suggests that the analgesic effect of deoxoglycyrrhetol dihemiphthalate and the related compounds is partially due to inhibition of PGE2 production.
Choline is an inhibitory modulator of cholinergic nerve function in guinea-pig colon
Authors: Trout S J , Burleigh D E 
Published: April 2011

Abstract
Using the novel smooth muscle-myenteric plexus (smmp) preparation from the guinea-pig colon, it has been possible to measure acetylcholine (ACh) overflow by a radiolabelling technique. The possibility that choline may be a modulator of cholinergic nerve activity in this preparation was investigated by observing its effects on electrically-evoked overflow of [3H]acetylcholine. Choline (72, 144 μM), in concentrations that did not contract the smmp preparation, caused a depression of electrically-evoked [3H]ACh overflow. This effect was unlikely to be due to actions on cholinesterase enzymes by end product inhibition. Choline also produced substantial non-muscarinic elevation of spontaneous [3H]overflow. It is concluded that inhibitory modulation of enteric cholinergic nerve activity by presynaptic muscarinic receptors may not be exclusively mediated by the actions of acetylcholine.
Ability of ketanserin to block different receptors in human placental vessels
Authors: Marin Jesus , Reviriego Jesus , Fernandez-Alfonso Maria S 
Published: April 2011

Abstract
5-Hydroxytryptamine (5-HT), noradrenaline (NA) and histamine induced concentration-dependent contractions in segments of human chorionic arteries and veins, whereas clonidine, an α2-adrenoceptor agonist, had no effect. 5-HT and histamine induced strong contractions, while NA elicited weak contractions in some segments. The maximal response was similar for 5-HT and histamine. The order of potency (EC50 values) was: 5-HT ≥ NA ≥ histamine. These agonists induced tachyphylaxis, and single concentrations caused transient contractions. Contractions elicited by 5-HT were antagonized by ketanserin, a 5-HT2-receptor antagonist, which also antagonized the responses to NA and histamine, but at greater concentrations than those needed for 5-HT responses. Contractions elicited by histamine were reduced by diphenydramine. Low concentrations of 5-HT amplified contractions caused by NA and histamine. The results indicate that: (i) 5-HT is the most potent constrictor agent tested in these vessels; (ii) its effects are mediated by 5-HT2-receptors; and (iii) ketanserin at therapeutic plasma concentrations (10−7 M) seems to block mainly 5-HT2-receptors, and α1-adrenergic- and H1-receptors to a small extent only.
β-Adrenoceptor antagonists and human sperm motility
Authors: Curtis-Prior P B , Gadd A L 
Published: April 2011

Abstract
Several β-adrenoceptor blocking agents have been evaluated for spermicidal activity using a transmembrane migration method. The rank order of potency of the active compounds was: penbutolol &gt; (+) - propranolol &gt; bufuralol &gt; (—) - alprenolol &gt; oxprenolol &gt; metoprolol. Atenolol, pindolol, practolol, tolamolol were without activity. The observed potencies of spermicidal activity are believed to be unrelated to β-blocking activities, and we have shown that whilst they are not predictable from lipid solubility or nonspecific membrane properties of the compound alone, both these aspects appear to play a role in this pharmacological activity.
Detection of Poly(I): Poly(C12U), Mismatched Double-stranded RNA, by Rapid Solution Hybridization: Blood Values after Intravenous Infusion
Authors: Strauss K I , Strayer D R , Gillespie D H 
Published: April 2011

Abstract
A rapid solution hybridization technique has been developed for estimating blood concentrations of poly(I):poly(C12U), a high molecular weight bioactive double-stranded RNA. Samples were prepared by mixing 100 μL of blood with, 165 μL of 6 M guanidine thiocyanate (GuSCN) and 0.16 M EDTA pH 8.0, and freezing. Hybridizations were carried out with a [3H]poly(C) probe in 3 M GuSCN for 10 min at 37°C. Ribonuclease-resistant hybrids were collected by precipitation with trichloroacetic acid and filtration. Validation studies demonstrated minor interassay variance; the assay was accurate in the range 0.1 to 10 ng poly(I):poly(C12U). Thirty-one blood samples from 15 patients were collected and prepared before and immediately after an average 35 min intravenous infusion of 40–500 mg poly(I):poly(C12U). Postadministration values averaged 48% (s.d. 23%) of the theoretical maximum (range 20–102%). These results confirm previous observations of rapid elimination kinetics of poly(I):poly(C12U) in patients.
Species-dependent differences in the properties of particulate cyclic nucleotide phosphodiesterase from rat and rabbit ventricular myocardium
Authors: Shahid M , Wilson M , Nicholson C D , Marshall R J 
Published: April 2011

Abstract
The ability of cyclic nucleotide phosphodiesterases (PDEs) to hydrolyse cyclic (c)AMP in rat and rabbit ventricular myocardium has been compared. The PDE activity of rabbit, but not rat, cardiac homogenate and supernatant fraction was potentiated by Ca2+/calmodulin and attenuated by cGMP. Both rabbit and rat ventricular myocardium were shown to have a membrane bound PDE. However, rabbit membrane-bound PDE was inhibited by cGMP and low concentrations of milrinone (IC50 2.7 μM). In contrast, rat membrane-bound PDE was not inhibited by either cGMP or low concentrations of milrinone (IC50 19 μM), but it was potently inhibited by rolipram (IC50 2.2 μM). Thus, in rabbit the particulate PDE is milrinone sensitive (PDE III) whilst in rat it is the rolipram sensitive (PDE IV) isoenzyme. There are clearly species differences in the intracellular localization and relative activities of PDE isoenzymes in cardiac tissue. This may explain the species differences already found in the activity of selective PDE isoenzyme inhibitors as inotropic agents.
Antidiabetic and aldose reductase activities of biflavanones of Garcinia kola
Authors: Iwu Maurice M , Igboko Ogo A , Okunji Chris O , Tempesta Michael S 
Published: April 2011

Abstract
Kolaviron, a mixture of C-3/C-8 linked biflavonoids obtained from Garcinia kola produces significant hypoglycaemic effects when administered intraperitoneally to normal and alloxan diabetic rabbits at a dose of 100 mg kg−1. The fasting blood sugar in normoglycaemic rabbits was reduced from 115 mg/100 mL to 65 mg/100 mL after 4 h. In alloxan diabetic rabbits, the blood sugar was lowered from 506 mg/100 mL to 285 mg/100 mL at 12 h. The hypoglycaemic effects have been compared with those of tolbutamide. Kolaviron inhibited rat lens aldose reductase (RLAR) activity, with an IC50 value of 5.4 × 10−6. The significance of these findings in the potential use of kolaviron as an antidiabetic agent is discussed.
Insulin absorption from conjunctiva studied in normal and diabetic dogs
Authors: Nomura M , Kubota M A , Sekiya M , Hoshiyama S , Imano E , Matushima Y , Ishimoto I , Kawamori R , Kamada T 
Published: April 2011

Abstract
The dynamics of insulin absorption from the ocular conjunctiva of anaesthetized normal and pancreatectomized dogs have been examined. A porcine insulin preparation of 1000 units mL−1 (pH 8.0) was administered as either 1 or 10 units kg−1 to the upper conjunctival sacs of recumbent dogs following an overnight fast. Plasma insulin concentrations increased significantly at 5 min after the insulin administration. Plasma glucose concentrations decreased significantly, in both normal (given 10 units kg−1) and diabetic dogs (given 1 unit kg−1 or 10 units kg−1). There was a dose-dependent increase in plasma insulin concentration following conjunctival administration. Estimated absorption was significantly higher in diabetic than in normal dogs.
Antihistaminic activity of pulegone on the guinea-pig ileum
Authors: de Urbina A V Ortiz , Martin M L , Montero M J , Carron R , Sevilla M A , San Roman L 
Published: April 2011

Abstract
Pulegone, a natural monoterpene compound, has an antihistamine effect on guinea-pig ileum. Its antagonism is of the competitive type (PA2 = 6.35) like that of mepyramine and dexchlorpheniramine, two H1-antagonists, with PA2 values of 10.15 and 8.74, respectively.