bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral 5‐HT2‐like receptors. Can they be classified with the available antagonists?
Authors: Leff P. , Martin G.R. 
Published: July 2012

Interactions between 5‐hydroxytryptamine (5‐HT) and the so‐called 5‐HT2 receptor antagonists ketanserin, spiperone, trazodone and methysergide were studied in isolated preparations of the rabbit aorta, rat jugular vein, and rat caudal artery.
Trazodone and spiperone were apparently simple competitive antagonists since they produced antagonism that was surmountable over the concentration range studied and, in each tissue, their apparent affinity appeared to be independent of the antagonist concentration. Furthermore, concentration‐ratios obtained with the two antagonists in combination suggested that antagonism was additive, implying mutual competition with a single population of 5‐HT receptors.
Ketanserin was a non‐surmountable antagonist of 5‐HT in the rat caudal artery and methysergide demonstrated surmountable, competitive antagonism only in the rabbit aorta.
Antagonist dissociation constants estimated for apparently competitive interactions showed that ketanserin, spiperone and trazodone expressed affinities which differed according to the tissue used. In the case of trazodone, affinity estimates differed by as much as 12 fold. These discrepancies were independent of the 5‐HT receptor agonist used and could not be attributed to an inadequate equilibration of the antagonist.
These results can be interpreted in two ways: either the receptors in the different tissues are heterogeneous or the antagonists used here must be considered as unreliable probes for the classification of 5‐HT2‐like receptors.
Autoradiographic localization of β‐adrenoceptors in pig lung using [125I]‐iodocyanopindolol
Authors: Goldie R.G. , Papadimitriou J.M. , Paterson J.W. , Rigby P.J. , Spina D. 
Published: July 2012

The binding of the β‐adrenoceptor radioligand [125I]‐iodocyanopindolol (I‐CYP) has been studied in pig lung parenchyma and the distribution of binding sites visualised by light microscopic autoradiography.
I‐CYP binding was saturable (maximum binding capacity Bmax = 51 ± 3 fmol mg−1 protein), involving sites with high affinity (dissociation constant KD = 73 ± 10 pM).
Specific I‐CYP binding was displaceable both by β‐adrenoceptor agonists ((−)‐isoprenaline > (−)‐adrenaline > (±)‐fenoterol > (−)‐noradrenaline > (+)‐isoprenaline > (±)‐RO363) and antagonists ((±)‐propranolol > ICI‐118551 > atenolol), indicating a predominance of β2‐adrenoceptors. Further analysis showed that displacement data for the β1‐selective antagonist atenolol and the β2‐selective antagonist ICI‐118551 were fitted best to a 2 binding site model and that both β1‐ and β2‐adrenoceptors were present in pig lung in the ratio 28:72 respectively.
Autoradiographic grains were localized over tissue and were most dense over alveolar walls > vascular endothelium > vascular smooth muscle > bronchial smooth muscle = bronchial epithelium. Atenolol (10−5 M) caused a 31 % reduction in specific grain density over alveolar wall tissue, while a 10 fold lower concentration of ICI‐118551 (10−6 M) caused a 50% decrease. These results are consistent with binding data in pig lung parenchyma demonstrating a mixed population of β‐adrenoceptors with a predominance of the β2 subtype.
Approximately 95 % of the parenchymal β‐adrenoceptors were associated with the alveolar wall as a mixed population of the β1 and β2 subtypes in the ratio 30:70 respectively. A greater proportion of the β‐adrenoceptors associated with bronchial and vascular smooth muscle seemed to be of the β2 subtype.
It is possible that the previously described relaxant responses of the pig lung parenchyma strip to β‐agonists, mediated via β2‐adrenoceptors, resulted from the sum of reactivities in airway and vascular smooth muscle together with relaxation of alveolar interstitial cells.
Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia
Authors: Giuliani Sandro , Maggi Carlo Alberto , Meli Alberto 
Published: July 2012

The cardiovascular (blood pressure, heart rate, cardiac contractility) effects of i.v. γ‐aminobutyric acid (GABA) were investigated in guinea‐pigs anaesthetized with barbitone or urethane.
GABA (0.1–10 mg kg−1) produced a transient ‘depressive’ effect on cardiovascular parameters which in barbitone‐anaesthetized animals was followed by a transient ‘excitatory’ effect. Resting cardiovascular parameters were higher in urethane‐ as compared to barbitone‐ anaesthetized animals.
Picrotoxin pretreatment (2 mg kg−1, i.v.) barely affected the cardiovascular changes produced by GABA in barbitone‐anaesthetized animals. In picrotoxin pretreated animals anaesthetized with urethane, GABA produced an initial depression of cardiovascular parameters followed by an excitatory phase.
Hexamethonium (20 mg kg−1, i.v) suppressed or reduced markedly the GABA‐induced cardiovascular changes both in barbitone‐ or urethane‐ anaesthetized animals.
Reserpine pretreatment lowered resting cardiovascular parameters. In these animals, regardless of type of anaesthesia, the effects of i.v. GABA were of the ‘excitatory’ type only. Reserpine pretreated animals anaesthetized with barbitone were selected for further experiments.
Various GABAA receptor agonists (homotaurine, muscimol, THIP, 5‐aminovaleric acid) mimicked the ‘excitatory’ effect of GABA in reserpine pretreated animals anaesthetized with barbitone and prevented the effects of subsequent GABA administration. On the other hand (±)‐baclofen, a selective GABAB receptor agonist, had a slight depressant effect and did not prevent the ‘excitatory’ cardiovascular effects of GABA.
Neither bicuculline nor picrotoxin pretreatment prevented the ‘excitatory’ cardiovascular effect of i.v. GABA in reserpine pretreated, guinea‐pigs anaesthetized with barbitone.
In adrenalectomized guinea‐pigs or in preparations receiving i.v. phentolamine plus propranolol, GABA produced only a small ‘depressant’ effect on cardiovascular parameters.
These findings demonstrate that GABA exerts a neuromodulatory effect on cardiovascular function via peripheral actions which is influenced by: (a) type of anaesthesia (b) resting values of cardiovascular parameters (c) degree of activity of the sympathetic nervous system and (d) catecholamine release from the adrenal medulla.
False labelling of dopaminergic terminals in the rabbit caudate nucleus: uptake and release of [3H]‐5‐hydroxytryptamine
Authors: Feuerstein T.J. , Hertting G. , Lupp A. , Neufang B. 
Published: July 2012

The effect of the catecholamine uptake inhibitor nomifensine and of the 5‐hydroxytryptamine (5‐HT) uptake blocker 6‐nitroquipazine on the accumulation of [3H]‐5‐HT (0.1 μM, 60 min incubation) and [3H]‐dopamine (0.1 μM, 30 min incubation) into slices of hippocampus and caudate nucleus of the rabbit was investigated. In addition, the influence of nomifensine on the electrically evoked [3H]‐5‐HT release from caudate nucleus slices and of nomifensine and 6‐nitroquipazine on [3H]‐5‐HT released from caudate nucleus slices was analysed.
In hippocampal slices, which contain practically no dopaminergic but densely distributed 5‐hydroxytryptaminergic and noradrenergic nerve terminals (ratio of dopamine:5‐HT:noradrenaline about 1:30:25), nomifensine (1, 10μM) did not affect the accumulation of [3H]‐5‐HT; 6‐nitroquipazine (1 μM) reduced [3H]‐5‐HT uptake to about 35% of controls. In the caudate nucleus, however, where dopamine is the predominant monoamine (ratio of dopamine:5‐HT:noradrenaline about 400:25:15) nomifensine (1, 10 μM) reduced the tritium accumulation to 65% whereas 6‐nitroquipazine (1 μM) was ineffective. The combination of both drugs (1 μM each) led to a further decrease to about 15%.
The uptake of [3H]‐dopamine into hippocampal slices was blocked by both nomifensine (1 μM) and 6‐nitroquipazine (1 μM) whereas in caudate nucleus slices only nomifensine (1, 10 μM) reduced the accumulation of [3H]‐dopamine. The combination of both drugs was not more effective than nomifensine alone. The different effects of both uptake inhibitors in the hippocampus and caudate nucleus suggest a neurone specific rather than a substrate specific mode of action.
In caudate nucleus slices incubated with [3H]‐5‐HT and superfused continuously the electrically evoked 5‐HT release was diminished by the D2‐dopamine receptor agonist LY 171555 and enhanced by the D2‐receptor antagonist domperidone. If, however, the labelling of caudate nucleus slices was performed in the presence of 1 μM or 10 μM nomifensine, the modulation of 5‐HT release via D2‐receptors was reduced or abolished, respectively. In the hippocampus both LY 171555 and domperidone were completely ineffective in modulating 5‐HT release regardless of the absence or presence of nomifensine.
The present results indicate that an inverse cross labelling of [3H]‐5‐HT into dopaminergic and of [3H]‐dopamine into 5‐hydroxytryptaminergic terminals may occur despite the low concentration (0.1 μM) of tritiated transmitters used. Such cross labelling, as demonstrated with the incubation period of 60 min in the caudate nucleus, may falsely indicate the existence of D2‐dopamine receptors modulating [3H]‐5‐HT release. If both 5‐hydroxytryptaminergic and dopaminergic terminals are present within the brain region under investigation false labelling can be corrected using neuronally specific uptake inhibitors.
Receptors for neurotransmitters in opossum oesophagus muscularis mucosa
Authors: Daniel E.E. , Jury J. , Robotham K.H. 
Published: July 2012

Muscularis mucosa of the distal oesophagus of the opossum contains nerves which release acetylcholine and substance P(SP)‐like material on field stimulation. The release of SP‐like material appeared to be inhibited by the presence of exogenous muscarinic agonists and potentiated by muscarinic antagonists. Analysis of the postjunctional receptors involved using carbachol, McNeil A‐343 (McN A‐343), atropine and pirenzipine suggested that the receptors were not typical M2‐muscarinic receptors. The potency of agonists and antagonists were consistent with some receptor properties resembling M1‐muscarinic receptors.
Prejunctional receptors to opiates, adenosine, agonists at α2‐adrenoceptors and prostaglandins were not detected.
Receptors for tachykinins were present on the muscle in this tissue, but did not resemble clearly either SP‐E or SP‐P type receptors. They appear to be undifferentiated since most tachykinins were of similar potency.
These results suggest that not all postjunctional muscarinic receptors in intestinal smooth muscle are M2 in type. There may be a gradation of types between M1 and M2.
Involvement of 5‐HT1A‐ and α2‐receptors in the decreased 5‐hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8‐hydroxy‐2‐ (n‐dipropylamino) tetralin
Authors: Marsden C.A. , Martin K.F. 
Published: July 2012

The 5‐hydroxytryptamine1A‐receptor agonist 8‐hydroxy‐2‐(n‐dipropylamino) tetralin (8‐OH‐DPAT, 0.1 mg kg−1 i.v.) decreased the height of the extracellular 5‐hydroxyindoleacetic acid (5‐HIAA) oxidation peak recorded in the suprachiasmatic nucleus (SCN) of the anaesthetized rat by use of differential pulse voltammetry.
The decrease in extracellular 5‐HIAA produced by 8‐OH‐DPAT could be partially attenuated by prior administration of the non‐selective 5‐HT receptor antagonist methiothepin (1 mg kg−1 i.v.). The 5‐HT2‐receptor antagonist ritanserin (0.2 mg kg−1 i.v.) did not appear to block the effects of 8‐OH‐DPAT.
The selective ligand for 5‐HT1A recognition sites TVX Q 7821 (isapirone, 1 mg kg−1 i.v.) decreased the extracellular level of 5‐HIAA in the SCN but to a lesser extent than 8‐OH‐DPAT. The response to 8‐OH‐DPAT was attenuated by prior administration of TVX Q 7821 to a level suggesting that TVX Q 7821 had blocked the effect of intravenous 8‐OH‐DPAT.
Idazoxan (0.2 mg kg−1 i.v.) an α2‐adrenoceptor antagonist, completely blocked the effect of 8‐OH‐DPAT on the 5‐HIAA oxidation peak recorded in the SCN, whilst having no effect on the 5‐HIAA oxidation peak when given alone.
At a dose of 0.5 mg kg−1 i.v. idazoxan induced a 120% increase in the height of the indole oxidation peak, suggesting that 5‐HT release and metabolism in the rat SCN may be influenced by tonic adrenergic inputs.
The data in this paper suggest that 5‐HT1A‐ and α2‐receptors are involved in the effects of i.v. administered 8‐OH‐DPAT on 5‐HT release and metabolism in the SCN in vivo.
Probenecid potentiates the hyperglycaemic effect but reduces the diuretic effect of frusemide in mice
Authors: Sandström Per‐Erik 
Published: July 2012

The effect of probenecid on frusemide‐induced diuresis and hyperglycaemia was studied in mice.
Probenecid, a known inhibitor of tubular secretion of organic anions in the kidney, strongly reduced the diuretic response to frusemide (25 or 200 mg kg−1 body weight). This effect of probenecid appeared to be dose‐dependent up to 240 mg kg−1 body weight, at least at the lower concentration of frusemide.
Pretreatment with probenecid (240 mg kg−1 body weight) potentiated the hyperglycaemic effect of frusemide (25 or 200 mg kg−1 body weight).
The results show that probenecid has opposite effects on frusemide‐induced diuresis and hyperglycaemia in mice. It is suggested that the acute hyperglycaemic effect of frusemide is not directly linked to diuresis.
An analysis of the action of pentobarbitone on the excitatory postsynaptic potentials and membrane properties of neurones in the guinea‐pig olfactory cortex
Authors: Richards C.D. , Strupinski K. 
Published: July 2012

Intracellular recordings were made from neurones in slices of guinea‐pig olfactory cortex maintained in vitro at 37°C. The average membrane potential was 63 ± 12 mV and the input resistance of these cells was 42 ± 20 MΩ (mean ± s.d.). Stimulation of the lateral olfactory tract (l.o.t.) generated a transient depolarization in these cells which had the characteristics of an excitatory postsynaptic potential (e.p.s.p.). If the e.p.s.p. was of sufficient amplitude it culminated in an action potential. The e.p.s.p. was potentiated by repetitive stimulation at 10–50 Hz and showed post‐tetanic potentiation after a prolonged period of high frequency stimulation (50–100 Hz for 30–60 s).
Pentobarbitone (0.1‐0.5 mM) depressed the e.p.s.p. reversibly but was without effect on the resting membrane potential, input resistance or time constant of the neurones. Pentobarbitone did not inhibit potentiation of the e.p.s.p. by a preceding conditioning shock.
It is concluded that pentobarbitone does not affect the passive membrane properties of neurones in the olfactory cortex. The depressant action of pentobarbitone on synaptic transmission results from a decrease in the amount of transmitter released in response to a nerve impulse, or a decrease in the sensitivity of the postsynaptic membrane to the transmitter or a combination of both effects.
Behavioural and adrenocortical responses to nicotine measured in rats with selective lesions of the 5‐hydroxytryptaminergic fibres innervating the hippocampus
Authors: Balfour D.J.K. , Benwell M.E.M. , Graham C.A. , Vale A.L. 
Published: July 2012

The effects of acute and subchronic (7) injections of nicotine (0.4 mg kg−1, s.c.) and of selective lesions of the 5‐hydroxytryptaminergic (5‐HTergic) pathways innervating the hippocampus on the spontaneous behaviour of rats in an elevated X‐maze composed of two open and two enclosed runways have been examined.
Subchronic, but not acute, nicotine increased total spontaneous activity. Neither acute nor subchronic nicotine altered the ratio of open:closed runway entries.
Destruction of the 5‐HTergic pathways innervating the hippocampus with 5,7‐dihydroxytryptamine caused a reduction in the ratio of open:enclosed runway entries.
Acute, but not subchronic, nicotine caused a significant increase in plasma corticosterone. The lesion had no effects on the plasma levels of this hormone.
No significant interactions between the lesion and the responses to nicotine were observed.
The data failed to provide any evidence that hippocampal 5‐HTergic systems may be implicated in the effects of nicotine on the spontaneous behaviour of the rat.
Effect of chronic treatment with 5‐HT1 agonist (8‐OH‐DPAT and RU 24969) and antagonist (isapirone) drugs on the behavioural responses of mice to 5‐HT1 and 5‐HT2 agonists
Authors: De Souza Rosemarie J. , Goodwin Guy M. , Green A. Richard , Heal David J. 
Published: July 2012

The effects of chronic (14 day) administration to mice of the 5‐HT1 agonists 8‐hydroxy 2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and 5‐methoxy‐3 (1,2,3,6‐tetrahydropyridin‐4‐yl) IH indole (RU 24969) on the hypothermic response to 8‐OH‐DPAT and the locomotor response to RU 24969 have been examined.
Chronic administration of 8‐OH‐DPAT (5 mg kg−1, s.c.) resulted in an attenuated hypothermic response to this drug given subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) but did not alter the locomotor response to RU 24969.
Chronic injection of RU 24969 (3 mg kg−1, i.p.) produced an attenuated locomotor response to this drug given i.p. or i.c.v. but not the hypothermic response to 8‐OH‐DPAT (0.5 mg kg−1, s.c).
Chronic administration of the putative presynaptic 5‐HT, antagonist isapirone (10 mg kg−1, i.p.) decreased the hypothermic response following 8‐OH‐DPAT injection but did not alter RU 24969‐induced locomotion.
Chronic treatment with 8‐OH‐DPAT (5 mg kg−1, s.c.) produced a modest enhancement of the 5‐HT2 receptor‐mediated head‐twitch behaviour initiated by 5‐hydroxytryptophan injection while chronic isapirone decreased this behavioural response. 5‐HT2 receptor number in frontal cortex was unaltered by isapirone treatment but markedly decreased (34%) by chronic 8‐OH‐DPAT.
These data suggest that chronic administration of the 5‐HT, agonists induces tolerance in their respective responses but not cross‐tolerance, while chronic isapirone may down‐regulate the 5‐HT1A site in a matter analogous to that seen by 5‐HT2 receptors following 5‐HT2 receptor antagonists.
The data further demonstrate that chronic treatment with 8‐OH‐DPAT and isapirone alter postsynaptic 5‐HT2 receptor function although 5‐HT2 receptor number in the frontal cortex did not correlate with the behavioural change.
Effects of α‐adrenoceptor agonists and antagonists on ouabain‐induced arrhythmias and cardiac arrest in guinea‐pig
Authors: Thomas George P. , Tripathi Rajit M. 
Published: July 2012

Effects of α‐adrenoceptor agonists and antagonists with different affinity for α1‐ and α2‐receptors on ouabain‐induced arrhythmias in guinea‐pigs were studied.
Early arrhythmias, ventricular fibrillation and cardiac arrest were induced in anaesthetized guinea‐pigs by the slow intravenous infusion of ouabain.
Phenylephrine and yohimbine potentiated the cardiotoxicity of ouabain significantly whereas prazosin and clonidine showed significant antiarrhythmic effects and delayed the cardiac arrest.
It is concluded that selective α1‐receptor stimulation and α2‐receptor blockade increases the cardiotoxic effects of ouabain and selective α2‐receptor stimulation and α1‐receptor blockade inhibits ouabain‐induced arrhythmias and cardiac arrest in guinea‐pigs.
The inflammatory response of rabbit skin to topical arachidonic acid and its pharmacological modulation
Authors: Aked D. , Foster S.J. , Howarth A. , McCormick M.E. , Potts H.C. 
Published: July 2012

The inflammatory reaction induced by the intradermal injection of arachidonic acid into the rabbit dermis has been investigated. Plasma extravasation was measured by the leakage of 125I‐albumin into the tissues and polymorphonuclear leukocyte (PMNL) accumulation was assessed histologically.
Arachidonic, 5,8,11,14,17‐eicosapentaenoic and 8,11,14‐eicosatrienoic acids, but not oleic, linoleic or linolenic acids, caused a concentration‐related plasma extravasation following their intra‐dermal injection. The plasma extravasation induced by arachidonic acid was dependent on PMNLs.
PMNL infiltration and plasma extravasation into arachidonic acid‐injected skin sites was inhibited by the mixed cyclo‐oxygenase‐lipoxygenase inhibitor, BW755C.
Arachidonic acid‐induced plasma extravasation was inhibited by cyclo‐oxygenase and 5‐lipoxygenase inhibitors but not by the Paf antagonist, kadsurenone.
The inflammation induced by arachidonic acid in the rabbit dermis may be a useful model for evaluating 5‐lipoxygenase inhibitors which could be potentially useful anti‐inflammatory agents for the treatment of psoriasis and other inflammatory diseases.
Mechanism of action of ketamine in the current and voltage clamped myelinated nerve fibre of the frog
Authors: Benoit E. , Carratù M.R. , Dubois J.M. , Mitolo‐Chieppa D. 
Published: July 2012

The effects of the general anaesthetic ketamine, on the frog isolated node of Ranvier, were studied under current and voltage clamp conditions.
Ketamine (0.5 and 1 mM) reversibly decreased the amplitude of the action potential and increased both the duration of the action potential and the threshold potential. When the K current was blocked, spontaneous action potentials appeared after washout of the drug.
Ketamine rapidly blocked the Na current and more slowly modified a fraction of Na channels (about 10%) to give rise to a non‐inactivatable (late) Na current. After washout of the drug, the block reversed more rapidly than the ketamine‐induced late Na current disappeared.
Steady‐state outward, peak Na and ketamine‐induced late Na currents were rapidly and reversibly blocked by ketamine with an apparent dissociation constant of 0.7 mM.
Both peak Na and ketamine‐induced late Na currents were reversibly blocked by procaine.
The primary afferent depolarizing action of kainate in the rat
Authors: Agrawal S.G. , Evans R.H. 
Published: July 2012

Dorsal roots (L3‐L7) isolated from immature (1–9 day old) rats were depolarized selectively by kainate (1–100 μM). L‐Glutamate (25–1000 μM), but not L‐aspartate, mimicked the action of kainate. N‐methylaspartate had no activity on these preparations and quisqualate was thirty times less active than kainate.
Depolarizations evoked by L‐glutamate (100–1000 μM) faded rapidly in the presence of L‐glutamate. Depolarizations evoked by kainate were depressed during the fade induced by L‐glutamate.
Certain electrically evoked C‐fibre volleys in dorsal roots or leg nerves of rats at any age were selectively depressed or abolished in the presence of kainate. The effect of kainate was more selective than that of γ‐aminobutyric acid or capsaicin.
Prolonged treatment of dorsal roots with kainate did not appear to be deleterious to C‐fibres.
It is suggested that certain primary afferent C‐fibres possess kainate receptors which may be activated physiologically by L‐glutamate released at their central terminations.