bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of local anaesthetics on the electrical and mechanical activity of the guinea‐pig ureter
Authors: Burdyga Th.V. , Magura I.S. 
Published: July 2012

The effects of local anaesthetic tertiary amines (procaine, lignocaine and tetracaine) as well as neutral (benzocaine) and permanently charged (QX‐314) local anaesthetics were studied on the evoked electrical and mechanical activity of the ureter smooth muscle.
‘Low’ concentrations of procaine and lignocaine (0.1‐1 mM) at pH 7.4 increased the duration of the slow plateau component of the evoked action potentials. The amplitude of the phasic contraction was consequently increased within the first 5 min of exposure. Tetracaine 0.1 mM caused a transient increase in the duration of the plateau and amplitude of the phasic contraction within the first 1–2 min only. The stimulant action of the local anaesthetics was greatly reduced in the presence of tetraethylammonium (TEA).
All the tertiary local anaesthetics caused depolarization of the membrane accompanied by an increase in the size of the electrotonic potentials. Lignocaine normally initiated the discharge of spontaneous action potentials.
High concentrations of lignocaine (5 mM) and tetracaine (0.5 mM) caused complete inhibition of the evoked action potentials and phasic contractions. Procaine 5 mM predominantly inhibited the contractile responses.
The permanently charged local anaesthetic QX‐314 (1 mM) caused an increase in the duration and amplitude of the plateau, increasing the number of spikes and the amplitude and duration of the phasic contraction. It also depolarized the ureter smooth muscle cells increasing the size of electronic potentials.
The neutral local anaesthetic benzocaine at 1 mM caused a reversible selective blockade of the plateau component of the evoked action potential and a gradual reduction in the amplitude of the phasic contraction. No change in either the membrane potential or the membrane conductance was observed.
High pHo (pH 9) significantly increased while low pHo (pH 6) decreased the inhibitory action of procaine and lignocaine but did not alter the effects of benzocaine and QX‐314.
Benzocaine caused a relaxation of the high‐K‐induced contraction, preferentially blocking the tonic component, whereas QX‐314 had no effect on the KCl‐contracture of the ureter muscle.
Two sites of action in the ureter smooth muscle cell membrane for local anaesthetics are suggested. One site interacts with local anaesthetics in a charged form, while the other one interacts with those in a lipid‐soluble neutral form. The charged form of local anaesthetics has a TEA‐like action, while the neutral form predominantly causes blockade of ‘slow’ Na/Ca channels.
Convulsant doses of penicillin shorten the lifetime of GABA‐induced channels in cultured central neurones
Authors: Chow Phoebe , Mathers David 
Published: July 2012

The influence of sodium benzylpenicillin (PCN) on membrane channels activated by γ‐aminobutyric acid (GABA) was studied in cultured spinal neurones of the mouse by the extracellular patch clamp technique.
In whole‐cell, current clamp recordings, concentrations of PCN above 0.2 mM significantly reduced the amplitude of the GABA response.
Single channel currents activated by GABA were studied in outside‐out patches of neuronal membrane. In both the absence and presence of PCN, cumulative open time distributions for GABA‐activated channels were well fitted by the sum of two exponential terms, characterized by fast (τf) and slow time constants (τs).
PCN (2 mM) reduced the mean value of τs from 4.29 ± 0.56 ms (mean ± s.e.mean) to 1.12 ± 0.09 ms but had no significant effect on τf.
The mean open time of GABA‐activated channels, calculated from the double exponential fits, decreased from 1.39 ± 0.35 ms to 0.53 ± 0.02 ms in the presence of 2 mM PCN.
The reduced mean open time of GABA‐sensitive channels seen in the presence of PCN may contribute to the convulsant action of the drug in vivo.
Pharmacological characterization of the receptor involved in chemoexcitation induced by adenosine
Authors: McQueen D.S. , Ribeiro J.A. 
Published: July 2012

Experiments were performed on cats anaesthetized with pentobarbitone in which carotid body chemoreceptor activity was recorded from the peripheral end of a sectioned carotid nerve.
Intracarotid (i.c.) injections of adenosine and its analogues, NECA (5′‐N‐ethylcarboxamidoadenosine), L‐PIA (L‐N6‐phenylisopropyladenosine), and D‐PIA (D‐N6‐phenylisopropyladenosine), caused dose‐related increases in chemosensory discharge. The rank order of potency as chemoreceptor stimulants was: NECA > adenosine > L‐PIA > D‐PIA.
Infusion of theophylline antagonized the chemoexcitatory effects of NECA, and infusion of 8‐phenyltheophylline (8‐PT), which is a more potent adenosine antagonist with less activity as a phosphodiesterase inhibitor, reduced the chemoexcitation induced by adenosine.
Infusion of 8‐PT (10 μg min−1 i.c.), a dose which substantially reduced the effect of injected adenosine, also reduced the sensitivity of carotid chemoreceptors to hypoxia (10% O2 for 4 min).
It is concluded that the adenosine receptors in the cat carotid body which mediate chemosensory excitation are xanthine‐sensitive and appear to be of the A2 sub‐type. Adenosine, released within the carotid body by physiological stimuli, may be involved in chemoexcitation.
The hypothermic action of carbachol in the rat brain periaqueductal grey area may involve neurotensin
Authors: Griffiths E.C. , Slater P. , Widdowson P.S. 
Published: July 2012

Neurotensin (NT) and carbachol both caused hypothermia when injected into the periaqueductal grey area (PAG) of rat brain.
Atropine prevented carbachol‐ but not NT‐induced hypothermia.
NT‐induced hypothermia was unaffected by various neurotransmitter agonists and antagonists in the PAG.
Both NT antibodies and thyrotrophin releasing hormone prevented carbachol hypothermia.
It is concluded that the hypothermic action of carbachol in the PAG is mediated via endogenous NT.
Structure‐activity relationships of alloxan‐like compounds derived from uric acid
Authors: Ashcroft Stephen J.H. , Harrison Donna E. , Poje Mirko , Rocic Boris 
Published: July 2012

The diabetogenic activity of a range of alloxan‐like compounds derived from uric acid has been investigated.
The classes of derivatives were: 5‐substituted‐isouric acids; 4,5‐disubstituted‐4, 5‐dihydrouric acids; 5‐substituted‐pseudouric acids; salts of dehydro‐uramil hydrate; salts of dehydro‐isouramil hydrate; alloxan derivatives.
Compounds were tested by intravenous injection into rats and diabetogenic activity assessed by production of persistent hyperglycaemia and glycosuria.
The only essential structural feature common to all active compounds was the presence of a quinonoid pyrimidine system or its hydrated equivalent. The presence of the five‐membered ring of uric acid (or an opened form thereof) did not abolish and in some compounds enhanced diabetogenic activity.
Hypersensitivity of mesenteric veins to 5‐hydroxytryptamine‐ and ketanserin‐induced reduction of portal pressure in portal hypertensive rats
Authors: Cummings Susan A. , Groszmann Roberto J. , Kaumann Alberto J. 
Published: July 2012

Isolated superior mesenteric veins from portal hypertensive rats were 3 to 10 times more sensitive to 5‐hydroxytryptamine (5‐HT) and 3 times less sensitive to (‐)‐noradrenaline than veins from sham‐operated rats. The sensitivity to vasopressin did not differ in the 2 groups.
Ketanserin competitively antagonized the effects of 5‐HT in superior mesenteric veins and portal veins with high affinity (KB values 0.1‐0.3 nM), as expected for 5‐HT2‐receptors. The affinity of ketanserin for 5‐HT2‐receptors was similar in veins from normal, sham‐operated or portal‐hypertensive rats.
Intraportal injections of low doses of 5‐HT caused increases in portal pressure which were more pronounced in portal hypertensive rats than in sham‐operated rats and were blocked by 0.3 mg kg−1 ketanserin in both groups. Ketanserin 0.3 mg kg−1 did not block the portal pressor response to (‐)‐noradrenaline in either group of rats.
In portal hypertensive rats but not in sham‐operated rats, 0.3 mg kg−1 ketanserin caused decreases in portal pressure, portal flow and cardiac output, as estimated by radioactive microspheres.
The reduction in portal pressure caused by ketanserin was due mainly to a decrease in portal venous inflow secondary to a decreased cardiac output. The reduction in cardiac output, which was observed only in the portal hypertensive rats but not in sham‐operated rats, is consistent with venous dilatation and pooling of blood in the portal venous system. The venous pooling could be secondary to the blockade of 5‐HT2‐receptors in the portal venous system. It is proposed that ketanserin should be explored for the treatment of patients with portal hypertension.
Role of cyclic GMP in the modulation by endothelium of the adrenolytic action of prazosin in the rat isolated aorta
Authors: Alosachie Iyad , Godfraind Théophile 
Published: July 2012

The effect of endothelium on the adrenolytic action of prazosin was studied in the rat isolated aorta.
Prazosin showed a non‐competitive type of antagonism in preparations with intact endothelium while in preparations where endothelium had been removed, prazosin at concentrations between 0.3 nM‐10 nM acted as a competitive antagonist.
Methylene blue, used to decrease tissue levels of guanosine 3′: 5′‐cyclic monophosphate (cyclic GMP), converted prazosin from a non‐competitive antagonist into an apparently competitive antagonist in the presence of endothelium.
Increasing tissue levels of cyclic GMP by incubation with 8‐bromo‐cyclic GMP converted prazosin from an apparently competitive antagonist into a non‐competitive antagonist in the absence of endothelium.
Analysis of concentration‐response curves for noradrenaline in the presence and absence of endothelium showed that the affinity for noradrenaline was the same but the efficacy, measured by estimating the receptor reserve, was not; it was lower in the presence than in the absence of endothelium.
It was concluded that the change in the mode of antagonism of prazosin after endothelium removal could be related to an alteration in the efficacy of the agonist, brought about by a change in the tissue levels of cyclic GMP.
Action of enflurane on cholinergic transmission in identified Aplysia neurones
Authors: Arimura Hiroyuki , Ikemoto Yoshimi 
Published: July 2012

Effects of enflurane on the cholinergic transmission in Aplysia neurones were studied by current and voltage clamp methods. Acetylcholine (ACh) evoked three types of postsynaptic responses on different identified neurones: (1) a depolarizing response due to an increase in Na and K conductances (D‐response), (2) a fast hyperpolarizing response due to an increase in Cl conductance (Cl‐response), and (3) a slow hyperpolarizing response due to an increase in K conductance (K‐response).
Enflurane altered neither the action potential nor the membrane resistance of the neurones but depressed the three ACh‐induced responses, non‐competitively, in a dose‐dependent manner. The K‐response was less suppressed than the other two.
Blockade of the closed state of ion channel was suggested by a reduction in the first ACh response evoked 1 min after administration of enflurane.
The anaesthetic facilitated the decay of the neurally evoked e.p.s.c. and i.p.s.c. in suggesting a reduction in the mean open time of the postsynaptic ion channel.
It is concluded that enflurane depresses excitatory and inhibitory cholinergic transmission by reducing the postsynaptic currents.
Plasma protein extravasation induced by mammalian tachykinins in rat skin: influence of anaesthetic agents and an acetylcholine antagonist
Authors: Couture Réjean , Kérouac René 
Published: July 2012

The effect of mammalian tachykinins on plasma protein extravasation was assessed in the rat dorsal skin. Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) increased vascular permeability in a dose‐related manner with a threshold dose of about 0.07 pmol in sodium pentobarbitone‐anaesthetized animals.
Plasma protein extravasation induced by the tachykinins was 100–500 times less in magnitude in animals anaesthetized with urethane.
Plasma protein extravasation induced by SP (66 pmol) was significantly reduced (63%; P < 0.001) by atropine (a muscarinic inhibitor) while that induced by NKA or NKB was unaffected by the inhibitor suggesting that a cholinergic component might only be involved in the vascular permeability elicited by SP.
The rank order of potency for the tachykinins on plasma protein extravasation was: NKB > SP > NKA (in absence of atropine) and NKB > NKA > SP (in presence of atropine), suggesting that this vascular response is mediated by a SP‐E‐receptor type.
The amplitudes of the plasma protein extravasation induced by NKB and its hydrophilic analogue [Arg°]NKB were similar, indicating that the lipophilic features of the native peptide cannot account for its potent biological activity.
Plasma protein extravasation was enhanced by the SP analogue [d‐Pro4, Lys6, d‐Trp7,9,10, Phe11] SP (4–11), thus showing the limitation of such SP analogues (antagonists) for characterizing the tachykinin receptors involved in vascular permeability.
A Contrasting effect of the diabetic state upon the contractile responses of aortic preparations from the rat and rabbit
Authors: Head Richard J. , Longhurst Penelope A. , Panek Robert L. , Stitzel Robert E. 
Published: July 2012

Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (65 mg kg−1). Rabbits were rendered diabetic by injecting alloxan (100 mg kg−1) into the lateral ear vein. Diabetes was confirmed by a significant elevation of serum glucose in both species 8 weeks after injection.
The maximum contraction to noradrenaline (NA), 5‐hydroxytryptamine (5‐HT) and KCl was markedly diminished in thoracic aortic rings (AR) from diabetic rats with no change in the EC50 of the agonists. There were no differences in the contractile properties of AR from diabetic rabbits to NA, 5‐HT or KCl. Diabetes did not alter the responsiveness of AR from the rat to angiotensin II (AII). However, AR from diabetic rabbits displayed a decreased maximal contraction and an increased EC50 to AII.
The magnitude of the acetylcholine‐induced relaxation to precontracted AR was not different between diabetic and control rats and rabbits.
The contractile responses of AR to NA, 5‐HT and KCl were depressed in diabetic rats, regardless of the control tissue to which they were compared. The decrease in maximal contraction to NA, 5‐HT and KCl seen in diabetic animals was prevented by insulin replacement.
The results demonstrated that while both rats and rabbits exhibited a similar degree of hyperglycemia after treatment with a diabetogenic agent, aortic preparations from the rabbit are not affected in the same way as the aorta from the diabetic rat when exposed to NA, 5‐HT and KCl. This feature may be related to the marked differences between the extent of sympathetic innervation of the aorta in the rabbit and rat. Furthermore, the decrease in maximal contraction in rat aorta was nonspecific with respect to agonists since it could also be demonstrated with KCl. Therefore, it follows that the diabetic state may affect processes responsible for contraction beyond the level of receptor activation.
Pharmacological characterization of binding sites identified in rat brain following in vivo administration of [3H]‐spiperone.
Authors: Chivers Jane , Jenner Peter , Marsden C. David 
Published: July 2012

[3H]‐spiperone is commonly used to label dopamine receptors in vitro in brain tissue. However, spiperone also interacts with brain 5‐hydroxytryptamine and noradrenaline receptors. In vivo, [3H]‐spiperone has been used for identifying dopamine receptors in both animals and man but the nature of the sites identified is unknown.
The in vivo administration of [3H]‐spiperone to rats leads to a selective accumulation of radioactivity in the olfactory lobes, tuberculum olfactorium, nucleus accumbens, striatum, substantia nigra, hippocampus, frontal cortex and hypothalamus, when compared to the cerebellum.
In vivo drug displacement studies suggest that the binding of [3H]‐spiperone in these areas may be to dopamine, 5‐HT or noradrenaline receptors.
[3H]‐spiperone in vivo mainly labels dopamine receptors in striatum, tuberculum olfactorium, hypothalamus, substantia nigra and olfactory lobes. However, in the frontal cortex and nucleus accumbens specific binding involves not only dopamine receptors but also 5‐HT and/or noradrenaline receptors.
Interpretation of in vivo studies in man using radioactive spiperone and its derivatives must take into account the fact that this ligand only labels dopamine receptors in some brain areas.
Modulation of GABAA receptor activity by alphaxalone
Authors: Cottrell Glen A. , Lambert Jeremy J. , Peters John A. 
Published: July 2012

The modulation of the γ‐aminobutyric acidA (GABAA) receptor by alphaxalone has been investigated by use of voltage‐clamp recordings from enzymatically isolated bovine chromaffin cells maintained in cell culture.
Alphaxalone (> 30 nm) reversibly and dose‐dependently potentiated the amplitude of membrane currents elicited by locally applied GABA (100 μm). The potentiation was not associated with a change in the reversal potential of GABA‐evoked currents and was not influenced by the benzodiazepine receptor antagonist, Ro15‐1788 (300 nm).
At relatively high concentrations (> 1 μm), alphaxalone directly elicited a membrane current. It is concluded that such currents result from GABAA receptor activation since they were reversibly suppressed by bicuculline (3 μm), dose‐dependently enhanced by phenobarbitone (100–500 μm), and had a similar reversal potential (∼ 0 mV) to currents elicited by GABA. Additionally, on outside‐out membrane patches, alphaxalone activated single channel currents with amplitudes and a reversal potential similar to those evoked by GABA.
Alphaxalone (30 nm‐1 μm) had no effect upon the amplitude of membrane currents elicited by locally applied acetylcholine (ACh) (100 μm). However, higher concentrations of alphaxalone (10–100 μm) reversibly suppressed ACh‐evoked currents, the IC50 for blockade being 20 μm.
The β‐hydroxy isomer of alphaxalone, betaxalone (100 nm‐1 μm), did not potentiate GABA‐induced currents, nor did higher concentrations of the steroid (10–100 μm) directly evoke a membrane current. However, over the latter concentration range, betaxalone suppressed the amplitude of currents elicited either by GABA or ACh.
The relevance of the present results to the anaesthetic action of alphaxalone is discussed together with the broader implications of steroidal modulation of the GABAA receptor.
Prostacyclin analogues reduce ADP‐ribosylation of the α‐subunit of the regulatory Gs‐protein and diminish adenosine (A2) responsiveness of platelets
Authors: Edwards Robert J. , MacDermot John , Wilkins Amanda J. 
Published: July 2012

Prostacyclin and adenosine activate adenylate cyclase in human platelet membranes and inhibit platelet aggregation. Results are presented which show that prolonged incubation of platelets with iloprost (a stable prostacyclin analogue) results in a reduction in the capacity for adenylate cyclase activation by the adenosine analogue 5′‐(N‐ethyl)‐carboxamidoadenosine (NECA), NaF, guanyl‐5′‐yl imidodiphosphate or GTP. However, iloprost pretreatment resulted in no change in the binding of [3H]‐NECA to platelet membranes.
These results contrast with those obtained after pretreatment with 2‐chloroadenosine which revealed no change in NaF or guanyl‐5′‐yl imidodiphosphate sensitivity of adenylate cyclase. Pretreatment with 2‐chloroadenosine resulted in reduced NECA‐dependent adenylate cyclase activation, and loss of [3H]‐NECA binding sites.
The heterologous desensitization of adenosine A2‐receptors by iloprost is accompanied by a loss (greater than 80%) of a 45 kDa protein from the plasma membrane, as revealed by [32P]‐ADP‐ribosylation in the presence of cholera toxin.
It is proposed that this example of heterologous desensitization is mediated by elimination of Gsα, a subunit of the stimulatory guanyl nucleotide‐binding regulatory protein.
Examination of the mechanisms involved in tetanic fade produced by vecuronium and related analogues in the rat diaphragm
Authors: Gibb A.J. , Marshall I.G. 
Published: July 2012

The effects of vecuronium (Org NC45), Org 7678 and Org 7684 were examined on twitches and tetani recorded from rat isolated diaphragms
Org 7678 and Org 7684 exhibited approximately one tenth of the neuromuscular blocking potency of vecuronium.
At concentrations producing equivalent amounts of twitch block, Org 7684 produced significantly less tetanic fade than did vecuronium or Org 7678.
In cut muscles both vecuronium and Org 7684 reduced the endplate current (e.p.c.) amplitude (Ie.p.c.), reduced e.p.c. decay time constant (ẗe.p.c.), and increased the e.p.c. train rundown.
The effects of vecuronium were not voltage‐dependent and vecuronium did not change ẗnoise.
The effect of Org 7684 on Ie.p.c. and ẗe.p.c. became greater with hyperpolarization, but the effect on e.p.c. train rundown was not voltage‐dependent.
It is concluded that both vecuronium and Org 7684 produce e.p.c. train rundown and tetanic fade by a prejunctional mechanism. However, whereas postjunctionally vecuronium blocks only the acetylcholine receptor, Org 7684 blocks both the receptor and its associated ion channel.
Cardiovascular effects of injections of vasopressin into the nucleus tractus solitarius in conscious rats
Authors: King Kathryn A. , Pang Catherine C. Y. 
Published: July 2012

The effects of injections of arginine vasopressin (AVP) into the nucleus tractus solitarius (NTS) on mean arterial pressure (MAP), heart rate (HR) and plasma concentrations of noradrenaline and adrenaline were investigated in conscious, unrestrained rats.
Injection of 2 ng AVP into the NTS significantly increased MAP but not plasma catecholamine concentrations, while injection of 10 ng AVP significantly increased MAP and plasma noradrenaline and adrenaline levels.
Neither dose of AVP produced any change in HR. The vehicle did not affect MAP, HR or plasma catecholamine levels.
Injection of a specific pressor antagonist of AVP, d(CH2)5Tyr‐(Me)AVP (10 ng), did not change MAP, HR or plasma noradrenaline or adrenaline levels.
These results suggest that the NTS is a central site of the pressor action of AVP. However, since the injection of the AVP antagonist did not reduce MAP or plasma noradrenaline or adrenaline levels, it suggests that AVP does not act tonically at the NTS to influence sympathoadrenal outflow.