bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein
Authors: Bregestovski P. , Bakhramov A. , Danilov S. , Moldobaeva A. , Takeda K. 
Published: July 2012

The membrane response to applied histamine of cultured endothelial cells from human umbilical vein was studied by use of whole cell and single channel patch clamp techniques. A value of −27 ± 1.4 mV was found for the resting potential under whole cell current clamp. No voltage‐gated currents were seen at either the macroscopic or single channel levels.
At holding potentials of −20 to −40 mV, histamine evoked slow rising, long lasting whole cell inward currents. The inward current was associated with depolarization and decreased input resistance. The calcium ionophore A23187 provoked similar whole cell inward currents.
Single channel currents were observed in cell‐attached and inside‐out patches for both histamine and A23187. The single channel conductance was about 20 pS with a mean open time of 5 ms and a reversal potential of 0 mV in symmetrical potassium solutions. Internal sodium blocked outward going currents.
For cell‐attached patches, histamine‐dependent channel activity required external calcium and was also seen when histamine was present in the bath but not the pipette. Recording from inside‐out patches revealed that decreases in ‘internal’ calcium resulted in the disappearance of channel activity.
The histamine‐dependent inward current appears to involve calcium‐dependent activation of cationic channels.
Prostaglandins involved in contractions by angiotensin II and bradykinin of isolated dog sphincter pupillae
Authors: Lu Wei , Okamura Tomio , Bian Ka , Inatomi Akihiro , Toda Noboru 
Published: July 2012

The dog isolated sphincter pupillae contracted in response to acetylcholine, angiotensin II (AII), bradykinin, prostaglandins F2α, D2, E2 and I2, and thionate thromboxane A2 (sTXA2) in a concentration‐dependent manner.
AII‐induced contractions were suppressed by treatment with saralasin, indomethacin, aspirin and diphloretin phosphate (DPP), a prostaglandin receptor antagonist. Contractions induced by bradykinin were also attenuated by indomethacin, aspirin and DPP. The amount of prostaglandin F2α (PGF2α) in the bathing media was increased approximately 41% following stimulation of the preparations by bradykinin.
The potency of contractile responses was in the order of PGF2α > PGD2 = sTXA2 > PGE2 > arachidonic acid > PGI2. Contractions induced by PGF2α were not significantly affected by treatment with indomethacin and ONO3708, an antagonist of the vasoconstrictor effect of prostaglandins, but appreciably attenuated by DPP. Arachidonic acid‐induced contractions were inhibited by indomethacin.
Contractions of dog iris sphincter muscle in response to AII and bradykinin may be mediated via substances synthesized by cyclo‐oxygenase from arachidonic acid. The distribution and nature of the prostaglandin receptors appear to differ markedly in iris sphincter and vascular smooth muscles.
H1‐ and H2‐receptor characterization in the tracheal circulation of sheep
Authors: Webber S.E. , Salonen R.O. , Widdicombe J.G. 
Published: July 2012

The effects of histamine, the specific H1‐agonist SKF 71481‐A2 and the H2‐agonist dimaprit were examined on tracheal vascular resistance in sheep anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. Changes in tracheal smooth muscle tone were also measured.
Histamine and SKF 71481‐A2 contracted the tracheal smooth muscle and this effect was blocked by the H1‐antagonist mepyramine. Stimulation of H2‐receptors with dimaprit had no effect on tracheal smooth muscle tone.
Histamine had a complex action on the tracheal vasculature producing either a triphasic change (early dilatation then constriction followed by late dilatation) or just a constriction. SKF 71481‐A2 always produced a biphasic change in vascular resistance (dilatation followed by constriction). Dimaprit dilated the tracheal vasculature.
The late dilatation produced by histamine in some sheep was blocked by bilateral cervical vagotomy but the mechanism for this effect is not known. No other responses to histamine, SKF 71481‐A2 or dimaprit were affected by vagotomy.
The vasoconstriction produced by histamine and SKF 71481‐A2 was antagonized by mepyramine indicating a H1‐receptor‐mediated effect. Cimetidine had no effect on the vasoconstriction to histamine suggesting a lack of involvement of H2‐receptors.
The vasodilatation produced by histamine and SKF 71481‐A2 was also antagonized by mepyramine, again suggesting a H1‐receptor‐mediated action. Cimetidine had no effect on the vasodilator response to histamine indicating no involvement of H2‐receptors in this response.
The dilator effect of dimaprit was antagonized by cimetidine suggesting this effect was mediated by H2‐receptors.
We conclude that H1‐receptors in the various parts of the sheep tracheal vasculature can cause increases and decreases in total tracheal vascular resistance; that H2‐receptors decrease resistance; and that the tracheal smooth muscle contracts on activation of H1‐receptors but has no response to H2‐agonists.
Quipazine reduces food intake in the rat by activation of 5‐HT2‐receptors
Authors: Hewson G. , Leighton G.E. , Hill R.G. , Hughes J. 
Published: July 2012

To determine which subtype(s) of 5‐hydroxytryptamine (5‐HT) receptor are involved in the anorectic action of quipazine, the ability of selective antagonists at 5‐HT2‐ and 5‐HT3‐receptors, and an antagonist at 5‐HT1‐like receptors, to block this response were investigated in non‐deprived rats, trained to eat a palatable diet.
Quipazine (0.5–8 mg kg−1, i.p.) produced a dose‐related reduction in the intake of palatable diet.
The anorectic effect of 4 mg kg−1 quipazine was antagonized by the nonselective 5‐HT‐receptor antagonist methysergide (5 mg kg−1, i.p.) and by the selective 5‐HT2‐receptor antagonists ketanserin (1 mg kg−1 and 2.5 mg kg−1, i.p.) and ritanserin (0.5 mg kg−1 and 1 mg kg−1, i.p.). The selective 5‐HT3‐receptor antagonist GR38032F (1 mg kg−1, i.p.) and (−)‐pindolol (4 mg kg−1, i.p.), which blocks some of the effects mediated at 5‐HT1‐like receptors, did not block the reduction in food intake produced by this dose of quipazine.
None of the 5‐HT‐receptor antagonists had any effect on food intake when they were administered alone, suggesting that endogenous 5‐HT is not involved in the tonic control of food intake under the conditions of these experiments.
It is concluded that the anorectic action of quipazine is mediated, at least in part, by activation of 5‐HT2‐receptors.
The modulatory role of vascular endothelium in the interaction of agonists and antagonists with α‐adrenoceptors in the rat aorta
Authors: Alosachie Iyad , Godfraind Théophile 
Published: July 2012

We have examined the effect of endothelium on the antagonistic action of prazosin, doxazosin, yohimbine and phentolamine against phenylephrine, clonidine and noradrenaline.
The action of prazosin against phenylephrine was similar to that earlier reported against noradrenaline, acting as a non‐competitive antagonist in the presence of endothelium and as a competitive antagonist in the absence of endothelium. Prazosin also acted as a non‐competitive antagonist against clonidine in the absence of endothelium.
Doxazosin behaved in a similar way to prazosin against noradrenaline, phenylephrine and clonidine acting as a non‐competitive antagonist in the presence of endothelium and as competitive antagonist after removal of endothelium. In contrast, yohimbine and phentolamine acted as competitive antagonists both in the presence and in the absence of endothelium.
Analysis of the concentration‐response curves for noradrenaline, phenylephrine and clonidine in the presence and in the absence of endothelium showed that the affinity for all three agonists was the same but not the efficacy and the receptor reserve, both of which were lower in the presence than in the absence of endothelium.
The rank order of agonist potency in the absence of endothelium was noradrenaline > phenylephrine > clonidine. The rank order of antagonist potency was prazosin ≥ doxazosin > phentolamine > yohimbine.
The results show that vascular endothelium modulates the contractile response to α‐adrenoceptor agonists and also modifies the action of the antagonists prazosin and doxazosin but not that of yohimbine and phentolamine. This effect of endothelium was related to a change in agonist efficacy and receptor reserve. These results also suggest that the α‐adrenoceptors of the isolated aorta of the rat are predominantly, if not exclusively of the α1‐subtype.
Pre‐and postjunctional actions of purine and xanthine compounds in the guinea‐pig caecum circular muscle
Authors: Hoyle Charles H.V. , Vladimirova Irina A. , Burnstock Geoffrey 
Published: July 2012

The sucrose‐gap technique was used to study pre‐and postjunctional actions of P1‐purinoceptor and P2‐purinoceptor agonists and a range of xanthine derivatives in the guinea‐pig caecum circular muscle.
Adenosine, 2‐chloroadenosine (2‐ClAd), ATP and α,β‐methylene ATP all caused concentration‐dependent hyperpolarization of the smooth muscle membrane with a rank order of potency of 2‐ClAd > α,β‐methylene ATP > adenosine.
The xanthine derivatives caffeine, theophylline, 8‐phenyltheophylline and 1,3‐dipropyl‐8‐(2‐amino‐4‐chlorophenyl) xanthine (PACPX) at submicromolar concentrations evoked depolarization of the smooth muscle membrane. At higher concentrations, all these compounds and enprofylline caused concentration‐dependent hyperpolarization.
All the purine compounds tested caused a reduction in the amplitude of the non‐adrenergic, non‐cholinergic inhibitory junction potential (i.j.p.). For the P1‐purinoceptor agonists adenosine and 2‐ClAd this was almost entirely a prejunctional effect. For the P2‐purinoceptor agonists this was mostly a postjunctional effect because both ATP and α,β‐methylene ATP caused significantly greater increases in the conductance of the smooth muscle membrane than did adenosine or 2‐ClAd.
All the xanthine compounds tested (up to 100 μm), except enprofylline, were capable of increasing the amplitude of the i.j.p. At millimolar concentrations both caffeine and theophylline could reduce the i.j.p. amplitude.
. It is concluded that there are inhibitory prejunctional P1‐purinoceptors on the i.j.p.‐producing neurones in the guinea‐pig caecum circular muscle and that, of the xanthine derivatives tested, none of them would be suitable to use as a P1‐purinoceptor antagonist in this preparation because of their own direct effects.
The β1‐adrenoceptor antagonist, betaxolol, is not released from the heart of the anaesthetized dog during sympathetic nerve stimulation
Authors: Duval N. , Lee C.R. , Eon M.T. , Petruzzo P. , Langer S.Z. 
Published: July 2012

We investigated the hypothesis that the β1‐adrenoceptor antagonist, betaxolol, can be accumulated by cardiac sympathetic nerve endings and then released together with noradrenaline during accelerans nerve stimulation.
Dogs were chronically treated with betaxolol (1 mg kg−1 daily, s.c.) for 7 days. Twenty four hours after the last dose, there was a significant retention of betaxolol in the heart of these dogs treated chronically with the β1‐adrenoceptor antagonist. However, during in vivo accelerans nerve stimulation, the concentration of betaxolol in the coronary sinus was not modified, whereas the noradrenaline concentration increased significantly.
Chronic betaxolol treatment antagonized the tachycardia induced by electrical stimulation of the cardiac accelerator nerves or by intravenous isoprenaline. However, the tachycardia induced by nerve stimulation was not antagonized to a greater extent than that induced by isoprenaline.
These findings are discussed in relation to a similar in vivo study in dogs treated with propranolol, in which the drug was found to be released into the coronary circulation during stimulation of the accelerans nerve.
Amino acid pharmacology in neocortical slices: evidence for bimolecular actions from an extension of the Hill and Gaddum‐Schild equations
Authors: Williams Thelma L. , Smith D.A.S. , Burton N.R. , Stone T.W. 
Published: July 2012

The equivalent circuit of the cortical slice preparation has been analysed to show that the measured d.c. voltages can be used to estimate the Hill coefficient for ligands acting on the pyramidal cell bodies.
The Gaddum‐Schild equation for agonist‐antagonist interactions has been modified for applications in which the Hill coefficient is not equal to 1.
The equations obtained have been applied to recent data of Burton et al. (1988). The results provide evidence for a bimolecular action of the agonists N‐methyl‐D‐aspartate (NMDA) and quinolinic acid and the antagonists kynurenic acid and 2‐amino‐5‐phosphono‐pentanoic acid at NMDA receptors on mouse neocortical pyramidal cells.
Development before and after hatching of non‐cholinergic excitatory innervation to the rectum via Remak's nerve in the fowl
Authors: Komori Seiichi , Matsuo Konomi , Ohashi Hidenori 
Published: July 2012

Development of the excitatory innervation to the rectal region of the intestine via Remak's nerve has been investigated in the rectum with Remak's nerve supply isolated from chicken embryos and young chicks aged less than two weeks.
Electrical stimulation of Remak's nerve produced a small contraction of the rectum isolated from chicken embryos on the 14th day of incubation (the earliest time examined). The contractile response was inhibited partially or totally by atropine (0.1 μg ml−1) but enhanced by physostigmine (0.01 to 0.05 μg ml−1), indicating its cholinergic nature.
During the embryonic stage, the proportion of the atropine‐resistant component in the contractile response increased, and the contractile response became almost entirely atropine‐resistant within the first week after hatching.
Later after hatching, the contractile response was increased in magnitude by atropine and reduced by physostigmine.
It is concluded that the excitatory innervation to the chicken rectum via Remak's nerve is cholinergic at the 14–16th day of incubation and is gradually replaced by a non‐cholinergic innervation during embryonic development.
Structural requirements of alloxan and ninhydrin for glucokinase inhibition and of glucose for protection against inhibition
Authors: Lenzen Sigurd , Brand Franz‐Hermann , Panten Uwe 
Published: July 2012

In order to elucidate the mechanism underlying the interactions between glucose and alloxan when competing for the sugar binding site of glucokinase from pancreatic B‐cells or liver, the structural requirements of the enzyme for inhibition by alloxan and for protection by glucose were determined.
With a half‐maximal inhibitory concentration of 5 μm, alloxan was the most potent pyrimidine derivative inhibitor of glucokinase. Uramil was a less potent enzyme inhibitor. A variety of other pyrimidine derivatives and related substances were ineffective.
Ninhydrin also inhibited glucokinase with a half‐maximal inhibitory concentration of 5 μm. Isatin was a slightly less potent enzyme inhibitor. Several other indoline derivatives were ineffective.
Only glucose derivatives with a sufficiently bulky substituent in position C‐2, such as the glucokinase substrates glucose and mannose and the inhibitors mannoheptulose, glucosamine, and N‐acetylglucosamine, protected glucokinase against inhibition by alloxan by binding to the active site of the enzyme. Glucose epimers which differed in other positions did not protect the enzyme against alloxan inhibition.
DTT (dithiothreitol) protected glucokinase against inhibition by alloxan and reversed the inhibition of the enzyme induced by alloxan. Thus the mechanism of glucokinase inhibition by alloxan and other inhibitors, such as uramil and ninhydrin, is an oxidation of functionally essential SH groups of the enzyme, where the most reactive keto group of the inhibitor acts as the hydrogen acceptor. The protective action of glucose and several C‐2 epimers demonstrates that these functionally essential SH groups are situated in the sugar binding site of the glucokinase.
The present results support our contention, that the pancreatic B‐cell glucokinase is the major target mediating the inhibition of insulin secretion by alloxan.
Local anaesthetic actions of cocaine: effects on excitatory and inhibitory synaptic responses in the hippocampus in vitro
Authors: Dunwiddie Thomas V. , Proctor William R. , Tyma Jennifer 
Published: July 2012

The basis for the proconvulsant action of cocaine was investigated in the CA1 region of the rat hippocampal slice in vitro.
Superfusion with 100 μm cocaine depressed inhibitory and excitatory postsynaptic potentials recorded intracellularly from CA1 pyramidal neurones; both types of potentials were inhibited to an equal extent. When inhibition was assessed using extracellular recording of population spike responses before and after conditioning impulses, there did not appear to be any selective effect upon either recurrent or feed‐forward γ‐aminobutyric acid (GABA)ergic inhibition.
Not all responses showed equivalent sensitivity to the local anaesthetic actions of cocaine. In particular, the antidromic population spike evoked by stimulation of the alveus was significantly more sensitive than the presynaptic fibre spike elicited by stimulation of stratum radiatum.
The rate of interictal spiking in hippocampus, induced by penicillin and increased potassium in the perfusion medium, was depressed by superfusion with cocaine in the range 5–100 μm.
These results suggest that cocaine does not have a selective depressant effect upon inhibitory pathways in the CA1 region of the hippocampus. Although the hippocampus shows epileptiform activity following systemic administration of local anaesthetics such as cocaine in the intact rat, this effect may not reflect a direct hippocampal site of drug action.
The dihydropyridine derivative 202–791: interpretation of the effects of the racemate considering inverse agonistic enantiomers
Authors: Damarowsky Marion , Lüllmann Heinz , Ravens Ursula 
Published: July 2012

The influence of the enantiomers and the racemate of the dihydropyridine derivative 202–791 [isopropyl 4‐(2,1,3‐benzoxadiazol‐4‐yl)−1,4‐dihydro‐2,6‐dimethyl‐5‐nitro‐3‐pyridinecarboxylate] on force of contraction and action potential was studied in guinea‐pig isolated papillary muscles. The effects were investigated during regular stimulation (1 Hz) and after a period of rest (10 min).
The enantiomers of the dihydropyridine derivative 202–791 had opposite effects on the mechanical and bioelectrical parameters: the (+,S)‐enantiomer enhanced contractility and prolonged action potential duration whereas the (‐,R)‐enantiomer reduced force and shortened action potential duration. Analogous to the effects during regular stimulation, the post‐rest adaptation was modified adversely: in the presence of the (+,S)‐enantiomer the pattern of adaptation was intensified while the (‐,R)‐enantiomer caused an attenuation. The term ‘inverse agonism’ seems more suitable than the commonly used comparison of agonist and antagonist, because each enantiomer possesses intrinsic activity, albeit in opposite directions.
The racemate of 202–791 acted like the (+,S)‐enantiomer. In concentrations up to 1μm, the racemate increased the force of contraction to the same extent as if the cardiodepressant (‐,R)‐enantiomer was not present. Only at the highest concentration (3 μm) did the counteracting effect of the (‐,R)‐enantiomer become evident. The racemate prolonged the action potential duration like the (+,S)‐enantiomer although to a lesser extent. Moreover, the typical post‐rest adaptation of contractile force and action potential duration was accentuated by the racemate as with the (+,S)‐enantiomer.
The results demonstrate that in case of 202–791, the effects of the racemate do not reflect the opposite actions of the two enantiomers, but rather mimic that of the (+,S)‐enantiomer. A prediction concerning the effects of the enantiomers which is based on findings obtained with the racemate is not possible.
Prostacyclin releases endothelium‐derived relaxing factor and potentiates its action in coronary arteries of the pig
Authors: Shimokawa Hiroaki , Flavahan Nicholas A. , Lorenz Robert R. , Vanhoutte Paul M. 
Published: July 2012

The possible interactions between prostacyclin and endothelium‐derived relaxing factor were examined, in isolated coronary arteries of the pig treated with indomethacin (10−5 m).
In organ chamber experiments, prostacyclin caused relaxations, which were potentiated in the presence of the endothelium; the potentiation was abolished by oxyhaemoglobin.
In bioassay experiments, prostacyclin caused minimal relaxations of bioassay rings without endothelium; these relaxations were potentiated when the bioassay ring was exposed to basally‐released endothelium‐derived relaxing factor (interaction between prostacyclin and basal endothelium‐derived relaxing factor) and further augmented when the endothelial cells were exposed to the prostanoid (stimulated release of endothelium‐derived relaxing factor). The endothelium‐dependent, but not the direct effects of prostacyclin were augmented by superoxide dismutase plus catalase and abolished by oxyhaemoglobin.
Forskolin, a direct activator of adenylate cyclase, caused relaxations of rings without endothelium, which were augmented by the presence of the endothelium.
The relaxations induced by prostacyclin or forskolin also had an endothelium‐dependent component in basilar and femoral arteries and in jugular veins of the pig.
The endothelium‐dependent actions of prostacyclin probably reflect activation of adenylate cyclase.
Agonists, antagonists and modulators of excitatory amino acid receptors in the guinea‐pig myenteric plexus
Authors: Luzzi S. , Zilletti L. , Franchi‐Micheli S. , Gori A.M. , Moroni F. 
Published: July 2012

The receptors for glutamic acid (L‐Glu) present in the guinea‐pig myenteric plexus‐ileal longitudinal muscle preparation have been studied by measuring the muscle contraction induced by numerous putative endogenous agonists acting at these receptors. Furthermore, the actions of different concentrations of antagonists, glycine, Mg2+ and Ca2+ on the ileal contractions induced by l‐G1u have been evaluated.
The EC50 values of the most common putative endogenous agonists of these receptors were: L‐Glu 1.9 × 10−5 m; L‐aspartate 8 × 10−5 m; quinolinate 5 × 10−4M; L‐homocysteate 1.4 × 10−4M; the dipeptide aspartyl‐glutamate 8 × 10−5m, while N‐acetyl‐aspartyl‐glutamate was inactive. Among the molecules used to classify excitatory amino acid receptors, N‐methyl‐D‐aspartate (NMDA) was the most potent (EC50 5 × 10−4m). Kainic and quisqualic acids were almost completely inactive.
The responses to L‐Glu were competitively antagonized by 2‐amino‐5‐phosphonovaleric acid. They were, also, prevented by hyoscine (10−7m) and by tetrodotoxin (3 × 10−7 m), suggesting that the L‐Glu‐induced ileal contraction was in some way dependent upon an action on the myenteric cholinergic neurones. Kynurenic acid was a non‐competitive antagonist, γ‐D‐glutamyl‐taurine (10−4m) and aminophosphonobutyric acid (10−4m) did not modify the L‐Glu‐induced contractions.
Glycine (10−5 m) significantly potentiated the effects of glutamate especially when the ionic composition of the superfusion medium contained concentrations of Ca2+ in the range of 0.6–1.2 mM. Strychnine 3 × 10−5 m did not modify the actions of glycine.
The data presented here confirm the presence of NMDA receptors in the guinea‐pig myenteric plexus, and show that these receptors, similar to those present in primary neuronal cultures may be modulated by glycine.