bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE BINDING CHARACTERISTICS OF [3H]‐DIHYDROERGOCRYPTINE ON INTACT HUMAN PLATELETS
Authors: ELLIOTT J.M. , GRAHAME‐SMITH D.G. 
Published: July 2012

We have characterized the binding of [3H]‐dihydroergocryptine to intact human platelets.
The values of the association and dissociation rate constants, affinity and capacity of specific [3H]‐dihydroergocryptine binding on intact cells closely resemble those previously reported on the human platelet lysate preparation.
The affinity of α‐adrenoceptor antagonists, determined from inhibition of [3H]‐dihydroergocryptine binding, is similar in intact and lysed platelet preparations, but the affinity of agonists is considerably lower in intact cells.
The potency of α‐adrenoceptor antagonists as inhibitors of noradrenaline‐induced platelet aggregation and as inhibitors of [3H]‐dihydroergocryptine binding on intact platelets demonstrate a significant correlation (r = 0.92, P <0.01).
The affinity and capacity of [3H]‐dihydroergocryptine binding to platelets from a group of healthy, young, male subjects show a high degree of consistency both between subjects (Kd = 2.81 ± 0.27 nm; Bmax = 63 ± 3 fmol/108 platelet: mean ± s.e. mean, n = 10) and between sampling occasions in a single subject (Kd = 3.28nm ± 13%; Bmax = 70 fmol/108 platelet ± 16%: mean ± coefficient of variation, n = 5).
There is no significant difference in the binding capacity of platelets from a group of elderly male subjects (mean age 73) compared to those from young males (mean age 27) or elderly females (mean age 77). The affinity of binding is slightly but significantly (P < 0.05) higher in the elderly male group compared to the two other groups.
We conclude that [3H]‐dihydroergocryptine binds to the α2‐adrenoceptor of intact human platelets which is responsible for noradrenaline‐induced platelet aggregation. The high consistency of the binding characteristics of [3H]‐dihydroergocryptine indicate that this assay may be useful as a monitor of platelet α‐adrenoceptor sensitivity in clinical investigation.
GLUCOCORTICOIDS INDUCE THE FORMATION AND RELEASE OF ANTI‐INFLAMMATORY AND ANTI‐PHOSPHOLIPASE PROTEINS INTO THE PERITONEAL CAVITY OF THE RAT
Authors: BLACKWELL G.J. , CARNUCCIO ROSA , DI ROSA M. , FLOWER R.J. , LANGHAM C.S.J. , PARENTE L. , PERSICO PAOLA , RUSSELL‐SMITH N.C. , STONE D. 
Published: July 2012

Dexamethasone and hydrocortisone induce the release of anti‐phospholipase proteins into the peritoneal cavities of rats.
Adrenocorticotropic hormone (ACTH) also releases these proteins in normal but not in adrenalectomized rats.
Peritoneal lavage proteins were separated by ion‐exchange and size exclusion chromatography. The anti‐phospholipase activity occurred in four separate fractions with the major component having an apparent mol. wt. of 40 k.
Column fractions containing these anti‐phospholipase proteins had anti‐inflammatory effects in the rat carrageenin pleurisy model whereas other fractions were inactive.
The proteins appear to be identical to macrocortin and lipomodulin, the ‘second messengers’ of glucocorticoid hormone action on the arachidonate system.
EFFECT OF ETYA AND BW 755c ON ARACHIDONATE‐INDUCED CONTRACTIONS IN THE GUINEA‐PIG ISOLATED TRACHEA
Authors: MITCHELL H.W. 
Published: July 2012

Arachidonic acid caused larger contractions in indomethacin‐treated guinea‐pig trachea than in control tracheae.
No change in contractions was obtained in tracheae treated with 5, 8, 11, 14, eicosatetraynoic acid (ETYA 10 μm).
ETYA (100 μm) blocked the effect of indomethacin on arachidonic acid‐induced responses. Likewise BW 755c (113 μm) reversed the effect of indomethacin.
The results show that arachidonate lipoxygenase products may be responsible for the contractile responses seen in the presence of indomethacin.
DISTRIBUTION AND TYPES OF ADRENOCEPTORS IN THE GUINEA‐PIG ILEUM: THE ACTION OF α‐ AND β‐ADRENOCEPTOR BLOCKING AGENTS
Authors: BAUER V. 
Published: July 2012

Transmurally stimulated segments of the guinea‐pig ileum have been used to analyse the different adrenoceptors in the terminal (0 to 3 cm) and the proximal (> 50 cm from the ileocaecal valve) ileum.
The prejunctional adrenoceptors (located on the final, cholinergic, motor nerve terminals) and postjunctional adrenoceptors (located on the smooth muscle membrane) have been characterized according to their sensitivity to α‐ and β‐agonists and antagonists.
Phentolamine, phenoxybenzamine and yohimbine, in concentrations of 0.1 μm, transiently enhanced (up to 10%) the twitch response. At higher concentrations all the α‐ and β‐antagonists studied depressed the neurogenic twitches and relaxed the smooth muscle.
The twitch‐inhibitory effects of adrenoceptor agonists (noradrenaline, adrenaline and ephedrine) were not antagonized by phenoxybenzamine (0.1, 0.5 and 1 μm), carbidine (0.5, 1 and 5 μm) and propranolol (0.5, 1 and 5 μm); however, they were depressed by phentolamine (0.1, 0.5, 1.25 and 5 μm) and yohimbine (0.25, 0.5 and 5 μm).
The smooth muscle contractions induced by noradrenaline and adrenaline in the terminal ileum and by phenylephrine in both the terminal and proximal ileum were antagonized by phenoxybenzamine, carbidine and phentolamine but were not influenced by yohimbine and propranolol.
The smooth muscle relaxations of the proximal ileum induced by noradrenaline, adrenaline and ephedrine were inhibited by yohimbine, phentolamine, carbidine and phenoxybenzamine, and the isoprenaline‐induced relaxation was antagonized by propranolol.
All the agonists studied, except phenylephrine, elicited relaxations of the acetylcholine‐induced sustained contraction of both proximal and terminal ileum. The relaxation induced by isoprenaline was antagonized by propranolol, and the effects of noradrenaline and ephedrine by yohimbine.
It is concluded that in the guinea‐pig ileum there are postsynaptic β‐adrenoceptors and at least two types of α‐adrenoceptors: α1‐excitatory postjunctional adrenoceptors activated by phenylephrine, noradrenaline and adrenaline and antagonized by phenoxybenzamine, carbidine and phentolamine; α2‐inhibitory prejunctional adrenoceptors activated by ephedrine, noradrenaline and adrenaline and inhibited by yohimbine and phentolamine. The inhibitory postjunctional α‐adrenoceptors are more close to the α2‐adrenoceptors, since they were stimulated predominantly by ephedrine and noradrenaline and inhibited by yohimbine.
It has been shown that all α‐adrenoceptor subtypes are to be found at every distance (0 to 70 cm) from the ileocaecal valve and that they can be activated in the resting or in the acetylcholine‐contracted states.
EFFECTS OF INHIBITORS OF ANAPHYLACTIC MEDIATORS IN TWO MODELS OF BRONCHIAL ANAPHYLAXIS IN ANAESTHETIZED GUINEA‐PIGS
Authors: ANDERSSON PER 
Published: July 2012

The effects of pretreatment with various inhibitors of anaphylactic mediators on antigen‐induced bronchoconstriction were studied in anaesthetized guinea‐pigs, actively sensitized according to two different regimens (one producing IgE‐ and IgG‐like antibodies and the other producing exclusively IgG antibodies).
The phospholipase A2‐inhibitors mepacrine and p‐bromphenacylbromide caused a dose‐dependent inhibition of the antigen‐induced bronchoconstriction in guinea‐pigs sensitized to produce both IgE and IgG antibodies. No effect was seen in those sensitized to produce only IgG antibodies.
In both models indomethacin pretreatment led to an increased anaphylactic bronchoreactivity, whereas mepyramine and FPL 55712 reduced it.
BW 755C significantly reduced antigen‐induced bronchoconstriction in guinea‐pigs sensitized to produce both IgE and IgG antibodies. In this model, the residual bronchoconstriction evident after combined pretreatment with indomethacin and mepyramine was prevented by additional pretreatment with mepacrine, FPL 55712 or budesonide.
Arachidonic acid given intravenously caused a marked bronchoconstriction that was prevented by indomethacin but not by budesonide, FPL 55712 or p‐bromphenacylbromide.
Although the same pattern of anaphylactic mediators is released in the two models of anaphylactic bronchoconstriction, a different activation mechanism is indicated by the results obtained with phospholipase A2 inhibitors.
EVIDENCE AGAINST THE UNITARY HYPOTHESIS OF AGONIST AND ANTAGONIST ACTION AT PRESYNAPTIC ADRENOCEPTORS
Authors: KALSNER STANLEY 
Published: July 2012

The concept that presynaptic receptors regulate noradrenergic transmitter release via a system of inhibitory receptors mediating negative feedback relies on a supposed association between increases in stimulation‐induced efflux of [3H]‐noradrenaline by antagonists and blockade by them of the inhibitory effects of exogenous noradrenaline.
It was shown in guinea‐pig ureter, that yohimbine (3 × 10−7 m), a presumed selective presynaptic antagonist, increased transmitter efflux substantially at 1 Hz and 5 Hz with 100 pulses, purportedly representing antagonism of the inhibitory effect of locally released noradrenaline but did not reduce the inhibitory effect of exogenous noradrenaline (1.8 × 10−6 m or 1.8 × 10−7 m) except in one case.
Additionally, the inhibitory effect of oxymetazoline (1.0 × 10−7m or 1.0 × 10−8m) on stimulation‐induced efflux was in no way antagonized by yohimbine (3 × 10−7 m).
It is concluded that the increased efflux of [3H]‐noradrenaline produced by antagonists and the decreased efflux produced by exogenous agonists may represent actions at different loci and that the hypothesis of presynaptic feedback regulatory sites is still not substantiated.
IRREVERSIBLE INHIBITION OF EPITHELIAL SODIUM CHANNELS BY ULTRAVIOLET IRRADIATION
Authors: CUTHBERT A.W. , FANESTIL D.D. , HERRERA F.C. , PRYN S.J. 
Published: July 2012

The effects of u.v. irradiation at 254 nm and 350 nm on sodium transport across frog skin epithelium have been investigated.
Irradiation at 254 nm but not at 350 nm produces a dose‐dependent, functionally selective blockade of sodium transport. The effect is apparently due to the irreversible closure of apical sodium channels.
The amiloride‐sensitive conductance was directly related to sodium transport as measured by short circuit current (SCC) both in normal and irradiated tissues, although both conductance and current were reduced in irradiated tissues.
The sensitivity of epithelia to irradiation at 254 nm was defined from the rate constants for the decline in SCC during three 2 min periods of irradiation at 1850 μW cm−2. The rate constant for the initial 2 min irradiation was 0.093 ± 0.008 min−1.
Lowering the sodium concentration to 5.5 mm from 110 mm increased the rate constant to 0.141 ± 0.014 min−1, consistent with the view that more functional sodium channels exist at lowered sodium concentration.
Lowering the temperature to 7°C from 23°C reduced the rate constant to 0.032 ± 0.007 min−1 suggesting that blockade of channels is not due to a direct interaction with photons.
Using a variety of experimental protocols we were unable to demonstrate that bromamiloride or iodoamiloride can act as photoligands for sodium channels in the epithelium of Rana temporaria. This is in contrast to earlier reports with other epithelia.
INFLUENCE OF NEONATALLY ADMINISTERED CAPSAICIN ON BARORECEPTOR AND CHEMORECEPTOR REFLEXES IN THE ADULT RAT
Authors: BOND SUSAN M. , CERVERO F. , McQUEEN D.S. 
Published: July 2012

Baroreceptor and chemoreceptor reflex activity was studied in anaesthetized adult rats which had been treated neonatally with a single injection of capsaicin (50 mg/kg s.c).
Pressor responses to bilateral carotid artery occlusion were significantly lower in capsaicin‐treated rats compared with vehicle‐treated controls. Pressor responses to intravenously injected noradrenaline were similar in the two groups of rats.
Resting respiratory minute volume and tidal volume were lower in anaesthetized capsaicin‐treated animals than in vehicle‐treated controls, but there was no significant difference in respiratory frequency.
The increases in respiration evoked by intravenous administration of the peripheral arterial chemoreceptor stimulant, sodium cyanide, or by breathing a hypoxic gas mixture, were significantly lower in capsaicin‐treated rats compared with the controls.
It is concluded that baroreceptor and chemoreceptor reflex activity are significantly reduced in anaesthetized adult rats which had been treated neonatally with capsaicin, and that this is likely to result from the destruction of unmyelinated baro‐ and chemoreceptor afferent fibres.
ANTICONVULSANT ACTIONS OF THE PUTATIVE γ‐AMINOBUTYRIC ACID (GABA)‐MIMETIC, ETHYLENEDIAMINE
Authors: MORGAN P.F. , STONE T.W. 
Published: July 2012

Ethylenediamine, 31.6–1000 mg/kg intraperitoneally, inhibited the convulsive effects of pentylenetetrazol, 100 mg/kg (i.p.) in mice.
Ethylenediamine, 100–1000 mg/kg (i.p.) increased the convulsion threshold to the intravenous infusion of three convulsants in the order pentylenetetrazol > bicuculline > strychnine.
The benzodiazepine antagonist Ro15–1788, 10 mg/kg (i.p.), significantly inhibited the anticonvulsant action of diazepam, 50 μg/kg, but not ethylenediamine, 1000 mg/kg.
These results clearly indicate that ethylenediamine has anticonvulsant properties and are consistent with the hypothesis that ethylenediamine is a γ‐aminobutyric acid (GABA)‐mimetic.
THE EFFECTS OF pH ON THE AFFINITY OF PIRENZEPINE FOR MUSCARINIC RECEPTORS IN THE GUINEA‐PIG ILEUM AND RAT FUNDUS STRIP
Authors: BARLOW R.B. , CHAN MARGARET 
Published: July 2012

Dose‐ratios obtained with pirenzepine on the guinea‐pig ileum at 30°C are indistinguishable from those obtained at 37°C.
In 0.1 m NaCl at 37°C the pKa of pirenzepine for the loss of its last ionizable proton is 8.2. The ionization of pirenzepine is therefore markedly affected by changes in pH in the physiological range.
In experiments with pirenzepine on guinea‐pig ileum and rat fundus made over a range of pH, the dose‐ratio increases with the proportion of the protonated form present. As expected, the slope of the graph of dose‐ratio against proportion protonated depends on the concentration of antagonist. The changes in pH produce only small effects on dose‐ratios obtained with pirenzepine monomethiodide. These effects of pH can account for some of the differences between estimates of the affinity of pirenzepine.
The logarithm of the affinity constant of the protonated form of pirenzepine for the receptors in guinea‐pig ileum is estimated to be 6.93, compared with 6.94 for the receptors in rat fundus. However, for the non‐protonated form the values appear to be below 5 for the ileum compared with about 6.4 for the rat fundus.
INVOLVEMENT OF THE MEDIAN RAPHE NUCLEUS IN ANTINOCICEPTION INDUCED BY MORPHINE, BUPRENORPHINE AND TILIDINE IN THE RAT
Authors: BRYANT ROSAMUNDE M. , OLLEY JEAN E. , TYERS M.B. 
Published: July 2012

Antinociception induced by three analgesics with differing profiles of activity, morphine, buprenorphine and tilidine, have been evaluated in the hot plate and paw pressure tests after administration by the subcutaneous route and directly into the median raphe nucleus in the conscious rat.
Behavioural and neurological effects of the three analgesics were also assessed.
The typical profiles of antinociceptive activity induced by the three analgesics were qualitatively similar after either route of administration. Morphine induced naloxone‐sensitive dose‐dependent effects in both tests. Buprenorphine showed naloxone‐sensitive effects with a bell‐shaped dose‐response curve in the thermal test but dose‐dependent activity in the pressure test. Tilidine induced naloxone‐sensitive dose‐dependent effects in the thermal test but demonstrated naloxone‐insensitive activity in the paw pressure test.
The behavioural and neurological effects of the analgesics in the dose range used would not have affected the animals' ability to respond to the nociceptive stimuli.
The results suggest that the median raphe could participate in drug‐induced antinociception. The mechanisms by which this might occur are discussed.
Therapy of organophosphate poisoning: the marmoset as a model for man
Authors: van Helden H.P.M. , van der Wiel H.J. , Wolthuis O.L. 
Published: July 2012

The ability of various bis‐pyridinium oximes to restore organophosphate‐inhibited neuromuscular transmission in vitro was compared in human intercostal and marmoset diaphragm muscles.
HI‐6 (2‐hydroxyiminomethyl‐pyridinium‐1‐methyl‐4′‐carbamoyl‐pyridinium‐1′‐methyl ether dichloride monohydrate) appeared very effective against VX (O‐ethyl S‐2‐diisopropylaminoethyl methylphosphonothioate) and sarin in both muscles, whereas obidoxim was quite effective against tabun.
Against soman, HI‐6, HS‐6 (2‐hydroxyiminomethyl‐pyridinium‐1‐methyl‐3′‐ carbamoylpyridinium‐1′‐methyl ether dichloride dihydrate) and obidoxim had little effect in the human muscle and only slight activity in the marmoset muscle; HGG‐12 (2‐hydroxyiminomethyl‐pyridinium‐1‐methyl‐3′‐phenylcarbonyl‐pyridinium‐1′‐methyl ether dichloride) and benzyl‐P2A (1‐benzyl‐2‐hydroxyiminomethyl‐pyridinium methanesulphonate) were ineffective.
Anaesthetized, atropinized marmosets were poisoned with soman (4 × LD50, i.v.) and subsequently treated with HI‐6, HS‐6 or HGG‐12. Only HI‐6 and HS‐6 were marginally effective in restoring respiration and neuromuscular transmission.
Marmoset muscle is a reasonable model for human muscle for the study of organophosphate poisoning and therapy.
Purine receptors in the guinea‐pig internal anal sphincter
Authors: Crema A. , Frigo G.M. , Lecchini S. , Manzo L. , Onori L. , Tonini M. 
Published: July 2012

In the isolated internal anal sphincter of the guinea‐pig, adenosine 5′‐triphosphate (ATP) and adenosine induced a concentration‐dependent and tetrodotoxin‐insensitive relaxation.
Pretreatment with theophylline (25–50 μm) had no significant effect on the concentration‐response curves obtained with either purine compound.
Reactive blue 2 (25–100 μm) shifted the curve to ATP to the right in a dose‐dependent fashion leaving that to adenosine unaltered. The antagonism appeared to be non‐competitive.
Neither reactive blue 2 nor purine receptor occupation by ATP or adenosine altered the electrically‐induced non‐adrenergic, non‐cholinergic inhibitory response.
The actions of ATP and adenosine in the guinea‐pig internal anal sphincter appear to be mediated by separate receptors. These receptors are not involved in the nerve‐mediated relaxation.
The inhibitory effects of 5‐hydroxytryptamine on gastric acid secretion by the rat isolated stomach
Authors: Canfield S.P. , Spencer J.E. 
Published: July 2012

The effect of 5‐hydroxytryptamine (5‐HT) on acid secretion by a rat isolated stomach preparation has been studied.
5‐HT at 10−5 M in the serosal bathing fluid produced significant inhibition of the acid secretory responses to histamine, pentagastrin and isoprenaline but was without effect on basal secretion or that due to bethanechol, dibutryl cyclic adenosine 3′,5′‐monophosphate (db cyclic AMP) or phosphodiesterase inhibition with ICI 63197. Increasing the concentration of 5‐HT to 5 × 10−5 m did not change this pattern of response whilst 5‐HT at 10−6 M did not cause consistent inhibition.
The inhibitory action of 5‐HT could be prevented by the antagonist methysergide (2.5 × 10−5 m). This concentration of methysergide alone did not affect responses to secretagogues or basal acid output.
Neither propranolol (2.5 × 10−5 m) nor tetrodotoxin (10−6 m) antagonized the inhibitory action of 5‐HT.
Both indomethacin (2.8 × 10−5 m) and ibuprofen (2.4 × 10−4 m) antagonized the action of 5‐HT. Indomethacin alone had no effect upon secretagogue responses.
5‐HT at 10−5 m had no inhibitory action when applied to the mucosal side of the preparation.
The results indicate that 5‐HT can act directly on the stomach of the rat to produce inhibition of acid output. This inhibition is selective and may involve the products of cyclo‐oxygenase activity.
A role for 5‐hydroxytryptamine in the GABA‐mimetic potentiation of α‐flupenthixol‐induced catalepsy in the rat
Authors: Davies John A. , Williams John 
Published: July 2012

α‐Flupenthixol (α‐FPT)‐induced catalepsy in the rat was potentiated by diaminobutyric acid (DABA), an inhibitor of the neuronal high affinity uptake of γ‐aminobutyric acid (GABA).
The depletion of 5‐hydroxytryptamine (5‐HT) with p‐chlorophenylalanine (PCPA) abolished the DAB A potentiation of α‐FPT‐induced catalepsy; this response was restored with 5‐hydroxytryptophan.
Potentiation of α‐FPT‐induced catalepsy by clonazepam was significantly reduced by methysergide. Conversely, the potentiation of catalepsy by clomipramine was significantly reduced by Picrotoxin.
These results are interpreted as evidence supporting a role for 5‐HT in modifying the GABA‐ergic inhibition of dopaminergic pathways, possibly by regulating the release of GABA.
Analysis of current noise evoked by nicotinic agonists in rat submandibular ganglion neurones
Authors: Gray P.T.A. , Rang H.P. 
Published: July 2012

The kinetics of the responses of rat submandibular ganglion neurones to nicotinic agonists were investigated by the analysis of agonist‐induced membrane current noise.
Two kinetic components are found in the responses of these cells to acetylcholine, carbachol, suberyldicholine, dimethyl‐4‐phenylpiperazinium and nicotine, in agreement with previous findings of two components in evoked synaptic currents in these cells.
Small, though significant, differences in the relative amplitudes of the two kinetic components were observed in the spectra of noise evoked by the different agonists. In particular, the fast component in the response to carbachol was relatively larger with respect to the slow component than with any other agonist tested.
No measurable dependence of the relative sizes of the two components on agonist concentration or membrane potential was observed.
The evidence supports the hypothesis that the two kinetic components are the product of two independent channel populations for which the agonists tested show some slight differences in selectivity.
The role of prostacyclin in modulating cholinergic neurotransmission in guinea‐pig ileum
Authors: Gaion R.M. , Trento M. 
Published: July 2012

The mechanism of action of prostacyclin (PGI2) on isolated segments of guinea‐pig terminal ileum was studied by recording the changes in isometric tension.
In these preparations PGI2 (1 nm‐1 μm) caused a concentration‐dependent increase in muscle tension. This effect was rapid and short‐lasting.
PGI2‐induced contractions were inhibited by atropine and potentiated by physostigmine.
Hemicholinium‐3 reduced the response to PGI2 and the inhibition was quantitatively comparable at any PGI2 concentration tested.
Tetrodotoxin as well as low temperature (20°C) abolished and β‐bungarotoxin reduced the effect of PGI2.
Hexamethonium decreased the response to submaximal, but not to maximal PGI2 concentrations.
PGI2 potentiated the twitch response of the ileum to electrical stimulation.
In the presence of tetrodotoxin, PGI2 did not alter the effect of a sub‐maximal concentration of acetylcholine (ACh).
The present results give indirect evidence for the ability of PGI2 to facilitate ACh release from intramural nerves possibly by increasing the excitability of cholinergic cell bodies.