bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐HT1 agonists reduce 5‐hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis
Authors: Sharp Trevor , Bramwell Steven R. , Grahame‐Smith David G. 
Published: July 2012

An intracerebral perfusion method, brain microdialysis, was used to assess changes of 5‐hydroxytryptamine (5‐HT) release in the ventral hippocampus of the chloral hydrate‐anaesthetized rat in response to systemic administration of a variety of 5‐HT1 receptor agonists.
A stable output of reliably detectable endogenous 5‐HT was measured in dialysates collected from ventral hippocampus with the 5‐HT reuptake inhibitor, citalopram, present in the perfusion medium.
Under these conditions the putative 5‐HT1A agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) caused a dose‐dependent (5–250 μg kg−1, s.c.) reduction of 5‐HT in hippocampal dialysates.
Similarly, the putative 5‐HT1A agonists gepirone (5 mg kg−1, s.c.), ipsapirone (5 mg kg−1, s.c.) and buspirone (5 mg kg−1, s.c.) markedly reduced levels of 5‐HT in hippocampal perfusates whereas their common metabolite 1‐(2‐pyrimidinyl) piperazine (5 mg kg−1, s.c.), which does not bind to central 5‐HT1A recognition sites, had no effect.
5‐Methoxy‐3‐(1,2,3,6‐tetrahydro‐4‐pyridinyl)‐lH‐indole (RU 24969), a drug with reported high affinity for brain 5‐HT1B binding sites, also produced a dose‐dependent (0.25–5 mg kg−1, s.c.) decrease of hippocampal 5‐HT output.
These data are direct biochemical evidence that systemically administered putative 5‐HT1A and 5‐HT1B agonists markedly inhibit 5‐HT release in rat ventral hippocampus in vivo.
The mechanism of action and pharmacological specificity of the anticonvulsant NMDA antagonist MK‐801: a voltage clamp study on neuronal cells in culture
Authors: Halliwell Robert F. , Peters John A. , Lambert Jeremy J. 
Published: July 2012

Some possible molecular mechanisms of action of the anxiolytic, anticonvulsant and neuroprotective agent MK‐801 have been examined in ‘whole‐cell’ voltage clamp recordings performed on rat hippocampal and cortical neurones, bovine adrenomedullary chromaffin cells and N1E‐115 neuroblastoma cells maintained in cell culture.
Transmembrane currents recorded from rat hippocampal and cortical neurones in response to locally applied N‐methyl‐d‐aspartate (NMDA) were antagonized by MK‐801 (0.1–3.0 μm). Blockade was use‐dependent, and little influenced by transmembrane potential. MK‐801 (3 μm) had no effect on currents evoked by kainate (100 μm).
The antagonism of NMDA‐induced currents by MK‐801 was only slowly and incompletely reversed when the cell membrane potential was clamped at −60mV during washout. Prolonged applications of NMDA at +40, but not −60 mV during washout, markedly accelerated recovery from block.
In contrast to MK‐801, ketamine (10 μm) blocked NMDA‐induced currents in a voltage‐dependent manner. Blockade increased with membrane hyperpolarization and was completely reversible upon washout.
MK‐801 (1–10 μm) produced a voltage‐ and concentration‐dependent block of membrane currents elicited by ionophoretically applied acetylcholine (ACh) recorded from bovine chromaffin cells. The block was readily reversible upon washout.
γ‐Aminobutyric acidA (GABAA) receptor‐mediated chloride currents of chromaffin cells were unaffected by MK‐801 (1–100 μm). In contrast, such currents were potentiated by diazepam (1 μm). MK‐801 (100 μmm) had no effect on currents evoked by GABA on hippocampal neurones.
MK‐801 (10 μm) had little effect on membrane currents recorded from N1E‐115 neuroblastoma cells in response to ionophoretically applied 5‐hydroxytryptamine (5‐HT). Such currents were antagonized by the 5‐HT3 receptor antagonist GR 38032F (1 nm) and also by MK‐801 at high concentration (100 μm).
Voltage‐activated, tetrodotoxin‐sensitive, sodium currents of chromaffin cells were unaffected by 10 μm MK‐801. However, at a relatively high concentration (100 μm), MK‐801 reduced the amplitude of such currents to approximately 77% of control.
The relevance of the present results to the central actions of MK‐801 is discussed.
Acute stress and GABAergic function in the rat brain
Authors: Losada Matilde E. Otero 
Published: July 2012

The function of the γ‐aminobutyric acid (GABA)‐ergic system in certain areas of the rat brain was investigated after acute (5 min) exposure to immobilization stress.
The activities of glutamate decarboxylase and GABA‐transaminase, GABA concentrations, GABA turnover in vivo and uptake of [3H]‐GABA were measured.
After 5 min of immobilization stress, GABA concentrations and [3H]‐GABA uptake were reduced, and GABA turnover stimulated in the olfactory bulbs. In contrast the uptake of [3H]‐GABA was increased in the corpus striatum after 5 min of immobilization stress.
None of the parameters measured was significantly altered by acute immobilization stress in the frontal cortex, hippocampus or medio‐basal hypothalamus.
These findings show that the olfactory bulbs and the corpus striatum are sensitive to the effects of acute stress. Since GABA in the olfactory bulbs is involved in the development of aggression and increased emotional state, it follows that neurochemical changes induced by acute stress might underlie some behavioural manifestations observed after stress.
Effects of peptidases on non‐adrenergic, non‐cholinergic inhibitory responses of tracheal smooth muscle: a comparison with effects on VIP‐ and PHI‐induced relaxation
Authors: Ellis James L. , Farmer Stephen G. 
Published: July 2012

The effects of peptidase enzymes on non‐adrenergic, non‐cholinergic (NANC) inhibitory responses of guinea‐pig trachea to electrical field stimulation (EFS), and on relaxations induced by vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) have been examined.
α‐Chymotrypsin reduced both the magnitude and, particularly, the duration of the inhibitory response to EFS, whereas papain reduced only the magnitude. Aprotinin, a peptidase inhibitor prevented the effects of α‐chymotrypsin but was without effect on papain.
α‐Chymotrypsin and papain both abolished relaxant responses to exogenous VIP and PHI. The action of α‐chymotrypsin was prevented by aprotinin, whereas that of papain was not affected.
The peptidases were without effect on concentration‐response curves to methacholine or to isoprenaline. It was also observed that, in the absence of the peptidases, aprotinin had no effect on inhibitory responses either to EFS or to exogenous VIP and PHI.
It is suggested that neuropeptides, possibly VIP and PHI, released during EFS of guinea‐pig trachea, partly mediate NANC relaxations, and that their action may be inhibited by peptidases. However, the lack of effect of aprotonin alone, on responses to EFS, suggests that, if endogenous peptidases are important in terminating the action of neuropeptides, they are resistant to the effect of this particular peptidase inhibitor. It is further suggested that neurogenic relaxation of guinea‐pig trachea is also partly mediated by a substance, possibly non‐peptide, other than VIP or PHI.
The effect of glucocorticosteroids on in vitro motility of the ureter of the sheep
Authors: Angelo‐Khattar Maria , Thulesius Olav , Cherian Thomas 
Published: July 2012

The effects of three glucocorticosteroids, hydrocortisone, methylprednisolone and dexamethasone, as well as two non‐steroidal anti‐inflammatory agents (NSAIDs) indomethacin and diclofenac sodium were tested in vitro on the spontaneously rhythmic contracting ureteral preparation of the sheep.
The NSAIDs and the steroids methylprednisolone (10−7‐10−4m) and dexamethasone (10−8‐10−4m), dose‐dependently inhibited ureteral motility. Hydrocortisone caused a cessation of spontaneous contractions only at the high concentration of 10−4 m.
Pretreatment of ureteral strips with the protein synthesis inhibitor cycloheximide (10−6m) abolished the inhibitory action of the corticosteroids on peristalsis, consistent with the suggestion that the action of steroids on the ureter is mediated via the synthesis of the anti‐phospholipase protein, lipocortin.
The potency of the steroids in descending order was found to be dexamethasone > methylprednisolone > hydrocortisone.
Effects of capsaicin desensitization on the stimulatory effect of kinins, prostaglandins, biogenic amines and various drugs in guinea‐pig isolated atria
Authors: Bernoussi Abderrahman , Rioux Francis 
Published: July 2012

A simple desensitization protocol was set up using capsaicin and isolated, spontaneously beating atria of guinea‐pigs to assess the possible participation of cardiac, capsaicin‐sensitive, substance P (SP)− and calcitonin gene‐related peptide (CGRP)‐containing sensory nerve fibres, in the cardiac stimulatory effects of bradykinin (Bk), kallidin (Kd), 5‐hydroxytryptamine (5‐HT), histamine, prostaglandin E2 (PGE2), prostaglandin E1 (PGE1), prostaglandin F2α, (PGF2α), adrenaline (Ad), glucagon, nicotine and angiotensin II (AII).
The positive chronotropic and inotropic effects of Bk, Kd and 5‐HT were markedly reduced in capsaicin‐desensitized atria compared to control. The percentage inhibition of the chronotropic and inotropic responses to the three agonists seemed to be inversely related to the concentration of agonist used and to vary also with the type of cardiac effect produced by the drug (for Bk the percentage inhibition was: 36–81% (chronotropic effect) and 62–86% (inotropic effect); for Kd: 61–78% (chronotropic effect) and 53–77% (inotropic effect); for 5‐HT: 25–66% (chronotropic effect) and 40–64% (inotropic effect)).
The positive chronotropic and inotropic effects of histamine, PGE1, PGE2, PGF2α, glucagon and AII had similar amplitudes in capsaicin‐desensitized and control atria.
The positive chronotropic and inotropic effects of Ad and nicotine were differentially affected by capsaicin desensitization. The inotropic effects of 7.5 × 10−7 and 7.5 × 10−6 m Ad were reduced by 41 and 27% respectively, in capsaicin‐desensitized atria compared to control. The chronotropic effects of 1.54 × 10−5 and 6.17 × 10−5 m nicotine were inhibited by 57 and 26% respectively, by capsaicin desensitization. On the other hand, the chronotropic effect of Ad and the inotropic action of nicotine were of similar amplitude in capsaicin‐desensitized and control atria.
These results were taken as an indication that a substantial part of the chronotropic and inotropic effects of Bk, Kd or 5‐HT in guinea‐pig atria, unlike those of histamine, PGE1, PGE2 PGF2α, glucagon and AII, might be the result of stimulation of capsaicin‐sensitive, SP‐ and CGRP‐ containing sensory nerve fibres. The slight, differential inhibition of the chronotropic and inotropic effects of Ad and nicotine by capsaicin desensitization suggests a minor contribution by cardiac, capsaicin‐sensitive sensory nerve fibres to the effects of nicotine and Ad in guinea‐pig atria.
Contractile effects of substance P and other tachykinins on the mouse isolated distal colon
Authors: Fontaine Jeanine , Lebrun Philippe 
Published: July 2012

Substance P (SP), physalaemin, eledoisin and kassinin induced concentration‐related contractions of the longitudinal muscle of the mouse distal colon. The responses were not antagonized by atropine (1.5 × 10−7 m), mepyramine (2.5 × 10−7 m), methysergide (5 × 10−7 m), timolol (10−6 m), phentolamine (10−6m) or naloxone (4 × 10−7m). They were enhanced by tetrodotoxin (TTX, 1.5 × 10−7 m). These observations indicate that the contractile responses to the tachykinins result from a direct activation of smooth muscle cells.
The contractile activity provoked by SP and physalaemin was inhibited by nifedipine (a Ca2+‐entry blocker) and was abolished in Ca2+ ‐free EGTA solution. Such data suggest that the myogenic effects of SP and physalaemin are mainly dependent on their ability to promote Ca2+ influx.
Eledoisin and kassinin evoked a contractile response in the absence of external Ca2+ and their myogenic activity was, to some extent, resistant to the inhibitory effect of nifedipine. This may indicate that an additional process, probably the release of an intracellularly bound Ca2+ store, participates in the mechanism by which eledoisin and kassinin contract the mouse distal colon.
After desensitization of the mouse distal colon to SP, the contractile activity provoked by SP or physalaemin was totally abolished whilst the responses evoked by eledoisin and kassinin were barely affected. These observations and other experimental findings indirectly support the assumption that the mouse distal colon could possess different tachykinin‐binding sites.
Analysis of the hyperpolarizing effect of catecholamines on canine cardiac Purkinje fibres
Authors: Neto Francisco Riccioppo , Sperelakis Nicholas 
Published: July 2012

The hyperpolarization induced by catecholamines on barium‐depolarized (0.2–0.8 mm BaCl) canine cardiac Purkinje fibres, in vitro, was studied by use of conventional microelectrode recordings of transmembrane electrical potentials.
Noradrenaline, adrenaline and isoprenaline hyperpolarized Purkinje fibres in a concentration‐dependent manner from a threshold concentration around 5 nm. The three catecholamines were shown to be approximately equipotent. Tachyphylaxis was observed when the interval between catecholamine applications was less than 15 min.
Atenolol (10 μm) blocked the hyperpolarization reversibly and theophylline (0.5 mm) potentiated it.
Tetrodotoxin (5 μm) did not affect the hyperpolarization induced by isoprenaline. Acetylcholine and histamine, up to 10 μm, were not effective in hyperpolarizing Purkinje fibres.
Low extracellular potassium concentrations (zero and 1 mm) did not affect the hyperpolarization, but high extracellular potassium concentrations (10–20 mm), markedly reduced the effect of isoprenaline (100 nm).
Reduction of the extracellular sodium concentration produced a roughly proportional reduction in the isoprenaline‐induced hyperpolarization. The hyperpolarization was reversibly blocked in 34 mm sodium Tris‐Tyrode solution.
The hyperpolarization was not reduced in Tyrode solution containing 0.6 mm calcium, but was drastically reduced in zero‐calcium Tyrode solution. This effect was reversible.
Addition of verapamil (5–10 μm) diminished the hyperpolarization, in a concentration‐dependent manner. This effect was partially reversed after washing.
Ouabain (0.7–1 μm) significantly reduced the isoprenaline‐induced hyperpolarization, but 2,4‐dinitrophenol (0.2 mm) did not affect it.
Caesium chloride (20 mm) abolished the hyperpolarization. The blockade was only partially reversed upon washing.
It is suggested that the hyperpolarization induced by a short exposure to catecholamines is mainly due to an increase in potassium permeability (PK). A mechanism involving calcium‐dependent potassium channels might underlie the increase in PK.
Effect of phorbol ester and pertussis toxin on the enhancement of noradrenaline release by angiotensin II in mouse atria
Authors: Musgrave Ian F. , Majewski Henryk 
Published: July 2012

Mouse atria were incubated with [3H]‐noradrenaline, and the outflow of radioactivity due to electrical field stimulation (5 Hz, 60 s) was used as an index of noradrenaline release. Angiotensin II (0.01 and 0.1 μm) significantly enhanced the stimulation‐induced (S‐I) outflow of radioactivity.
Phorbol 12‐myristate 13‐acetate (0.001, 0.03, 0.1 and 1.0 μm), a protein kinase C activating phorbol ester, significantly enhanced the S‐I outflow of radioactivity. When angiotensin II (0.1 μm) was present with the concentration of phorbol 12‐myristate 13‐acetate that was maximally effective in increasing the S‐I outflow (0.1 μm), the enhancement of S‐I outflow produced by angiotensin II was maintained.
Polymyxin B (70 μm), an inhibitor of protein kinase C, significantly inhibited the S‐I outflow. Polymyxin B also inhibited the enhancement of the S‐I outflow produced by angiotensin II (0.1 μm).
In another series of experiments mice were injected with pertussis toxin (1.5 μg per mouse), 4 days before their atria were removed. The effectiveness of pertussis toxin pretreatment was determined indirectly using carbachol. Carbachol caused a concentration‐dependent fall in both the rate and force of beating of isolated spontaneously beating atria from mice pretreated with vehicle. This effect of carbachol was not seen with atria from mice pretreated with pertussis toxin.
Pertussis toxin pretreatment did not alter the enhancement of the S‐I outflow of radioactivity produced by angiotensin II (0.01 and 0.1 μm).
These results suggest that angiotensin II receptor modulation of noradrenaline release is not mediated through either a pertussis toxin sensitive guanine nucleotide‐binding protein or activation of protein kinase C.
Swim‐stress‐induced antinociception in young rats
Authors: Jackson Helen C. , Kitchen Ian 
Published: July 2012

Opioid and non‐opioid mechanisms have been implicated in the phenomenon of stress‐induced antinociception in adult rodents. We have studied stress‐induced antinociception in developing rats and characterized differences in the neurochemical basis of this effect in pre‐ and post‐weanling animals.
Twenty and 25 day old rats were stressed using warm water (20°C) swimming for 3 or 10 min periods and antinociception was assessed by the tail immersion test (50°C).
A 3 min swim in 20 and 25 day old rats produced marked antinociception which was blocked by naloxone, Mr 1452, 16‐methyl cyprenorphine and levallorphan but not Mr 1453 or N‐methyl leval‐lorphan. The δ‐opioid receptor antagonist ICI 174,864 attenuated stress‐induced antinociception in 25 day old rats but was without effect in 20 day old animals.
A 10 min swim in 25 day old rats produced antinociception which was non‐opioid in nature. In contrast, antinociception was not observed in 20 day old rats after a 10 min swim‐stress.
Pretreatment of animals with dexamethasone blocked 3 min swim‐stress antinociception in 20 and 25 day old animals but had no effect on antinociception induced by a 10 min swim.
Swim‐stress‐induced antinociception can be observed in young rats and dissociated into opioid and non‐opioid types dependent on the duration of swimming stress. The non‐opioid type appears to develop more slowly and cannot be observed in preweanling rats. The opioid type is a predominantly μ‐receptor phenomenon in preweanling animals but δ‐receptor components are observable in postweanling rats.
Development of cholinergic nerve transmission in the chick oesophagus
Authors: Miyazaki Hideto , Taneike Tetsuro , Ohga Akira 
Published: July 2012

The onset and development of cholinergic mechanisms in the smooth muscle of the chick oesophagus were studied by estimating the changes in mechanical response and biochemical parameters between 9 days of incubation and 7 days after hatching.
Transmural and vagal nerve stimulation first evoked contraction in the oesophagus at 10 days and 11 days of incubation, respectively. These contractions were inhibited by atropine (1–2 μm) and potentiated by physostigmine (0.2 μm). On the other hand, hexamethonium (200 μm) had an inhibitory effect on vagal nerve stimulation but not on transmural nerve stimulation.
The relative amplitude of contraction induced by both vagal nerve and transmural stimulations compared to high K+ (80 mm)‐induced contractions, progressively increased with age in embryos up to 19 days of incubation.
The activity of choline acetyltransferase (ChAT), an enzyme synthesizing acetylcholine (ACh), also gradually increased in the oesophagus during the period from 9 days to 19 days of incubation, which was similar to the change in the nerve‐mediated contraction. On the other hand, the cholinesterase activity reached a maximum at 13 days of incubation and decreased until 7 days after hatching.
The contractile response to ACh and binding sites of [3H]‐quinuclidinyl benzilate ([3H]‐QNB) were observed in the oesophagus at 9 days of incubation. The maximum response produced by ACh (300 μm) tended to be greater in early stages (9–13 days of incubation) than in later stages. The sensitivity estimated from pD2 values increased up to 15 days of incubation. During the embryonic period, the number of muscarinic receptors estimated from the binding of [3H]‐QNB changed very little.
These results suggest that in the chick oesophagus, extrinsic and intrinsic cholinergic innervation start to function at 10 days and 11 days of incubation, respectively and continue to develop progressively up to the time of hatching. It seems likely that the functional and biochemical maturation of receptive mechanisms on the smooth muscle precede those of cholinergic innervation.
Modulation of phospholipase A2 activity in human fibroblasts
Authors: Solito Egle , Parente Luca 
Published: July 2012

Human embryonic skin fibroblasts (HSF) incubated overnight with either human recombinant interleukin‐1α (rIL‐1α) or interleukin‐1β (rIL‐1β) released large amounts of prostaglandin E2 (PGE2).
rIL‐1β, bradykinin (Bk) and arachidonic acid (AA) significantly stimulated PGE2 release from HSF incubated overnight in the presence of either interleukin.
Hydrocortisone inhibited the PGE2 release induced by rIL‐1β and Bk, but not by AA.
The steroid inhibitory effect was reversed by actinomycin D as well as by an anti‐lipocortin monoclonal antibody.
The results suggest that in HSF, rIL‐1β is able to stimulate both cyclo‐oxygenase and phospholipase A2 (PLA2) activity.
The stimulation of PLA2 activity by rIL‐1β is inhibited by hydrocortisone, probably via induction of lipocortin‐like proteins.
Variable, voltage‐dependent, blocking effects of nitrendipine, verapamil, diltiazem, cinnarizine and cadmium on adrenomedullary secretion
Authors: López Manuela G. , Moro María A. , Castillo Carlos F. , Artalejo Cristina R. , García Antonio G. 
Published: July 2012

Catecholamine release from cat adrenal glands perfused at a high rate (4 ml min−1) at 37°C with modified Krebs solutions lacking Ca and containing 1.2 mm K (hyperpolarizing solution) or 118 mm K (depolarizing solution) was triggered by 10‐s pulses of Ca (0.5 mm) in the presence of 118 mm K. Hyperpolarized glands released 1280 ± 135 ng per pulse and depolarized glands 831 ± 98 ng per pulse (n = 29).
While the dihydropyridine Ca channel blocker nitrendipine inhibited secretion in hyperpolarized glands with an IC50 of 214 nm, in depolarizing conditions the drug was much more potent (IC50 = 0.99 nm). In contrast, the inorganic Ca channel blocker cadmium inhibited secretion with the same potency both in hyperpolarized or depolarized glands.
Cinnarizine, diltiazem and verapamil exhibited intermediate degrees of voltage‐dependence in blocking secretion. The IC50 ratios between hyperpolarized and depolarized glands were 215, 36, 19, 8 and 0.76 respectively for nitrendipine, cinnarizine, diltiazem, verapamil and cadmium. Because the experimental design (strong depolarization in the absence of Ca) favours the highest opening probability of Ca channels, it seems that these drugs bind preferentially to their receptors when these channels are in their open state.
Variable voltage‐dependent effects of the five Ca channel blockers on adrenomedullary catecholamine release suggests different sites and mechanisms of action on, or near L‐type Ca channels in chromaffin cells. In addition, these findings might help to explain why these drugs exhibit tissue selectivity and why they act differently in normal polarized as compared to ischaemic depolarized cells.