bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of chlormethiazole on single unit activity in rat brain; interactions with inhibitory and excitatory neurotransmitters
Authors: Gent J.P , Wacey T.A. 
Published: July 2012

Extracellular recordings were made of single unit activity in the brainstem of urethane anaesthetized rats. Drugs were applied by microiontophoresis from multibarrelled micropipettes or administered intraperitoneally.
Chlormethiazole (CMZ) caused a decrease in spontaneous firing rate when applied with high currents (>40 nA).
When applied with lower currents CMZ did not cause changes in firing rate, but enhanced the inhibitory effects of γ‐aminobutyric acid (GABA), muscimol and glycine in a dose‐dependent manner. The inhibitory actions of acetylcholine were not affected.
Excitatory responses to glutamate and acetylcholine were unaffected by applications of CMZ which caused potentiation of GABA, muscimol and glycine. When applied at higher currents CMZ caused a decrease in the response to glutamate.
Intraperitoneal administration of CMZ (50–600 μmol kg−1) also enhanced responses to microiontophoretically applied GABA, muscimol and glycine.
These results are compared with those reported for other anticonvulsant drugs and possible mechanisms of action of CMZ are discussed.
Effects of sodium and calcium concentrations on the potentiation by indomethacin of the responses of rabbit mesenteric and coeliac arteries to vasoconstrictor agonists
Authors: Novelli Ethel L.B. , Oshiro Maria E.M. , Paiva Antonio C.M. , Paiva Therezinha B. 
Published: July 2012

The contractile responses of the rabbit isolated coeliac and mesenteric arteries to five agonists (angiotensin, adrenaline, histamine, acetylcholine and 5‐hydroxytryptamine), but not to K+, were potentiated by indomethacin (8.4 μm)
The potentiation was similar whether indomethacin was added 1 h before or during the response to the agonist.
The agonists that were more potentiated by indomethacin were also more dependent on the Ca2+ concentration in the medium, for their contractile action.
Prostaglandin E2 in low concentrations (micromolar) did not affect the resting tone but relaxed the agonist‐contracted arteries both in normal and in Ca2+‐free medium.
No prostaglandin E (PGE)‐like substances were detected in the perfusate of arteries contracted by angiotensin.
Reduction of the external Na+ concentration to 80 mm resulted in potentiation of the responses to agonists (angiotensin and adrenaline), but not to K+, and in this Na+‐deficient medium potentiation by indomethacin was greatly reduced.
These results suggest that potentiation by indomethacin of the arteries' responses to vasoactive substances may result from that drug's inhibitory action on sodium influx and consequent increase in calcium entry through receptor‐operated channels.
The contractile response to and the release of noradrenaline by transmural nerve stimulation in the guinea‐pig vas deferens and a comparison with the response to noradrenaline
Authors: Gillespie J.S. , Macrae I.M. 
Published: July 2012

The release of noradrenaline from the guinea‐pig vas deferens by transmural stimulation was measured electrochemically after separation by h.p.l.c. Variations in release with different durations of stimulation were then compared with the mechanical response during stimulation.
During long periods of 270 s of stimulation at 10 Hz the average release of noradrenaline in the final 250 s remained at about 50% of that released during the first 20 s yet the mechanical response throughout the later time declined to near zero.
Superfusion with constant concentrations of noradrenaline produced mechanical responses similar to those from transmural nerve stimulation, an initial rapid contraction declining to a low level of maintained activity. During the later period, when the response to infused noradrenaline was low, the twitch response to transmural stimulation was potentiated.
Phentolamine 10−6 m reduced the potentiation of the twitch response to transmural stimulation by noradrenaline and propranolol 10−6 m enhanced the potentiation.
These results suggest that the decline in the adrenergic component of the response to prolonged transmural nerve stimulation is not the result of a decline in noradrenaline release but mainly due to desensitization to the contractile effect of noradrenaline. Since the similar desensitization produced by infused noradrenaline does not reduce the twitch response to transmural nerve stimulation it is unlikely that the transmitter responsible for that component is noradrenaline.
The pharmacological modulation of [3H]‐disaturated phosphatidylcholine overflow from perifused lung slices of adult rats: a new method for the study of lung surfactant secretion
Authors: Gilfillan A.M. , Hollingsworth M. , Jones A.W. 
Published: July 2012

Lung slices from adult rats incubated in [methyl‐3H]‐choline chloride formed [3H]‐disaturated phosphatidylcholine ([3H]‐DSPC) which was used as an index of lung surfactant.
The slices were perifused after 3 h incubation in [methyl‐3H]‐choline chloride and the overflow of [3H]‐DSPC, as a rate coefficient, was used as a measure of surfactant secretion. The basal overflow of [3H]‐DSPC rapidly declined over the first 30 min of perifusion and then declined slowly.
Salbutamol induced a prolonged, and sometimes delayed, increase in [3H]‐DSPC overflow, which was reduced by (±)‐propranolol. Potassium chloride produced an immediate, and usually transient, increase in [3H]‐DSPC overflow which was not modified by atropine or (±)‐propranolol. Adenosine 5′‐triphosphate, but not phenylephrine, also increased [3H]‐DSPC overflow.
This method can measure the magnitude and time‐course of lung surfactant secretion induced by drugs.
Differential anatomical location of [3H]‐N,n‐propylnorapomorphine and [3 H]‐spiperone binding sites in the striatum and substantia nigra of the rat
Authors: Hall M.D. , Jenner P. , Kelly E. , Marsden C.D. 
Published: July 2012

Specific [3H]‐spiperone and [3H]‐N,n‐propylnorapomorphine (NPA) binding was measured in striatum and substantia nigra of the rat following unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the medial forebrain bundle, kainic acid lesions of the substantia nigra or striatum, and following decortication.
Binding sites labelled by [3H]‐spiperone in striatum were found to lie on striatal cell bodies and on the terminals of cortico‐striate glutamate fibres, but not on presynaptic dopamine terminals. In contrast, binding sites labelled by [3H]‐NPA were demonstrated on striatal cell bodies and on the terminals of nigro‐striatal dopamine fibres, but not on cortical afferents.
In substantia nigra, specific [3H]‐spiperone binding sites were found only on non‐dopamine cell bodies. No clear evidence was found for their existence on dopamine cell bodies, the terminals of strio‐nigral fibres or the terminals of cortico‐nigral fibres. In contrast, specific binding sites for [3H]‐NPA were found on dopamine cell bodies and the terminals of strio‐nigral fibres. Localization on non‐dopamine cell bodies or on cortico‐nigral fibres was not demonstrated.
These studies support the concept of differential localization of agonist and antagonist binding sites.
Glycine‐induced changes in acetylcholine release from guinea‐pig brain slices
Authors: Beani Lorenzo , Bianchi Clementina , Siniscalchi Anna , Tanganelli Sergio 
Published: July 2012

The effect of glycine (Gly) on acetylcholine (ACh) release from superfused, resting or electrically‐stimulated slices of guinea‐pig caudate nucleus (CN), brain stem (BS) and cerebral cortex (CC) was studied.
The amino acid 1 × 10−4‐6 × 10−3mol l−1 reduced the electrically‐induced release and increased the spontaneous and KCl‐evoked transmitter outflow, mostly in CN but also in BS, whereas it was ineffective in CC. Taurine, chosen as a structurally related compound, moderately affected only the spontaneous release in CN.
Strychnine 2 × 10−7 mol l−1 was per se ineffective, but prevented most Gly effects. The Gly‐induced increase of ACh outflow in resting CN slices, however, could be completely antagonized only by administering strychnine and picrotoxin together.
These findings suggest that: (i) the overall pattern of Gly influence on cholinergic function is similar to that previously described for γ‐aminobutyric acid (GAB A); (ii) specific receptors seem to be present in BS and, above all, in CN; (iii) a positive cooperation between endogenous GAB A and Gly is evident in resting CN slices; (iv) the absence of any apparent endogenous glycinergic control on the cholinergic neurones casts doubt on but does not exclude the existence of glycinergic neurones in CN.
Importance of physico‐chemical properties in determining the kinetics of the effects of Class I antiarrhythmic drugs on maximum rate of depolarization in guinea‐pig ventricle
Authors: Campbell Terence J. 
Published: July 2012

The effects of Class I antiarrhythmic drugs on the maximum rate of depolarization of guinea‐pig ventricular action potentials were studied by standard microelectrode techniques.
The ability of seven different drugs to depress in unstimulated tissue (‘resting block’) was found to correlate poorly with the lipophilicity (log P) of the compounds and only a little better with their molecular weights.
Depression of in stimulated tissue was studied for 11 drugs and found, in all cases, to increase with stimulation frequency (‘rate‐dependent block’).
The rapidity of onset of rate‐dependent block (at approximately equipotent concentrations) varied markedly between drugs. It correlated well with molecular weight (r = 0.83; P < 0.01).
The time constant of recovery from rate‐dependent block (ire) also correlated very well with molecular weight (r = 0.94; P < 0.001) for the seven drugs thus studied.
A simplified model for the interaction of Class I drugs with the fast sodium channel is proposed in which the drugs all act as ‘inactivation enhancers’; (as suggested by other workers) but in which their molecular weight plays a central role in determining the kinetics of this interaction.
Sgd 101/75: cardiovascular effects in various animal preparations; interactions with vascular postjunctional α1‐ and α2‐adrenoceptors
Authors: Mathy M.J. , Thoolen M.J.M.C. , Timmermans P.B.M.W.M. , van Zwieten P.A. 
Published: July 2012

The effect of the imidazolidine Sgd 101/75 (2‐[2‐methylindazol‐4‐imino]‐imidazolidine HCl) on blood pressure, as well as its α‐adrenoceptor agonist activity and affinity for these receptors, were examined in various animal preparations.
After both intravenous administration to conscious spontaneously hypertensive rats and intravenous injection or infusion via the vertebral artery in chloralose‐anaesthetized cats, Sgd 101/75 (1–10 mg kg−1) elicited pressor responses. Intracisternal application of Sgd 101/75 (1 mg kg−1) to chloralose‐anaesthetized cats did not affect blood pressure.
In the pithed rat and pithed cat the vasopressor responses to i.v. Sgd 101/75 were effectively antagonized by prazosin (0.1–1.0 mg kg−1, i.v.) but much less by yohimbine (1 mg kg−1, i.v.).
Sgd 101/75 proved a less potent and less selective displacing agent of [3H]‐clonidine‐ and [3H]‐prazosin‐binding in rat brain membranes than clonidine.
The results suggest that Sgd 101/75 is a selective α1‐adrenoceptor agonist, devoid of any centrally or peripherally mediated hypotensive activity; this is probably caused by the low capacity of Sgd 101/75 for stimulating α2‐adrenoceptors.
Neonatal capsaicin treatment impairs vasopressin‐mediated blood pressure recovery following acute hypotension
Authors: Bennett T. , Gardiner S.M. 
Published: July 2012

Rats were treated with a single injection of either capsaicin (50 mg kg−1 s.c.) or vehicle on day 2 after birth. When the animals were adult, they were challenged with osmotic (water deprivation) and haemodynamic (acute hypotension) stimuli that normally evoke vasopressin release.
Capsaicin‐treated and vehicle‐injected rats showed similar body weight losses and plasma osmolalities following 48 h of water deprivation. Thus it appears that neonatal treatment with capsaicin does not impair the antidiuretic response to plasma hyperosmolality.
Following acute ganglion blockade in the presence of angiotensin converting enzyme inhibition, there was some recovery of blood pressure in the vehicle‐injected rats, but recovery was significantly (P < 0.001) less in the capsaicin‐treated animals. The recovery may be attributed to vasopressin since it was abolished by an antagonist selective for the pressor action of the peptide (d(CH2)5DAVP).
These results suggest that neonatal treatment with capsaicin impairs vasopressin‐mediated recovery of blood pressure following acute hypotension. The possible involvement of baro‐ or chemoreceptor afferents is discussed.
Biphasic effect of methylxanthines on acetylcholine release from electrically‐stimulated brain slices
Authors: Pedata Felicita , Pepeu G. , Spignoli G. 
Published: July 2012

The effect of caffeine and aminophylline on the release of acetylcholine (ACh) was investigated in slices of rat cortex perfused with Krebs solution at rest and during electrical stimulation at frequencies of 0.2, 1 and 5 Hz.
Both methylxanthines added to the supervising Krebs solution at a concentration of 50 μm enhanced ACh release. Conversely, at a concentration of 0.5 mm both caffeine and aminophylline decreased ACh release.
Neither caffeine nor aminophylline affected the unstimulated ACh release.
Dipyridamole 10 μm potentiated the inhibitory effect of adenosine 30 μm on ACh release and antagonized both the stimulatory and inhibitory effects of caffeine on ACh release.
The inhibitory effect of caffeine was antagonized by cyclohexyladenosine (CHA) 0.5 μM and N‐ethylcarboxamideadenosine (NECA) 5 μm.
The results indicate that methylxanthines exert both stimulatory and inhibitory effects on ACh release by acting on adenosine receptors. Methylxanthines may enhance the electrically‐evoked ACh release by antagonizing the effect of endogenous adenosine on inhibitory adenosine receptors. On the other hand the mechanism through which methylxanthines decrease ACh release remains obscure.
Some characteristics of the long‐latency component of the evoked muscle response induced by administration of catechol to the anaesthetized rat: a neurophysiological and neuropharmacological investigation
Authors: Dewhurst D.G. 
Published: July 2012

Administration of catechol to rats anaesthetized with urethane produces a central excitatory state during which an EMG consisting of three temporally distinct components (M1, M2 and M3) can be recorded from forelimb and hindlimb muscles to electrical stimulation of cutaneous afferents.
The probability of occurrence of all three components was measured in flexor and extensor muscles of fore‐ and hindlimb and showed that the long latency component (M3) occurred less frequently in hindlimb muscles than forelimb and that its probability of occurrence in hindlimb extensors was significantly reduced as compared to flexors. A possible reflex pathway for this long latency component of the EMG is suggested.
Phenobarbitone (5 mg kg−1 i.v.) had no significant effect on the probability of occurrence of M1, M2 or M3.
These results suggest that the long latency component (M3) is not due to activation of a spino‐bulbo‐spinal reflex as has been previously suggested.
Cholinoceptor blocking drugs were found to reduce significantly the probability of occurrence of M2 and M3 and anticholinesterases to increase the probability of M2. None of the drugs was found to affect the short latency M1 component of the EMG. These results are discussed in relation to the possible reflex pathways of all three components of the EMG.
Pathophysiological mechanisms of sudden death induced by platelet activating factor
Authors: Lefer Allan M. , Müller Hugo F. , Smith J. Bryan 
Published: July 2012

Platelet activating factor (Paf) (15–40 μg−1) kills male rabbits within 3 to 5 min. Intravenous injection of Paf at a dose of 15 μg kg−1 is uniformly lethal, and the rabbits died within 4.5 ± 0.4 min.
The sudden death is characterized by cessation of respiration, a marked decrease in mean arterial blood pressure (M.A.B.P.), and 8 fold increases in plasma thromboxane B2 (TxB2) concentrations with only modest elevation in plasma 6 keto‐prostaglandin F1α (6‐keto PGF1α) concentrations.
Pretreatment with the cyclo‐oxygenase inhibitor, ibuprofen (6.25 mg kg−1), or with the thromboxane synthetase inhibitors dazoxiben (2.5 mg kg−1), CGS‐13080, or OKY‐046 1 mg kg−1) increased survival rates to 83–100%.
Protected rabbits showed only modest changes in M.A.B.P. and no significant increase in plasma TxB2 concentrations. The protective drugs showed a dose‐related action on M.A.B.P., plasma TxB2 concentration and mortality rate in Paf‐induced sudden death.
The mechanisms of the protection appeared to be prevention of platelet aggregation (leading to pulmonary thrombosis) and pulmonary and coronary vasoconstriction. However, Paf does not appear to exert direct vasoconstrictor effects in isolated coronary or pulmonary arteries.
The effects of Paf in vivo appear to be mediated by TxA2 released by activated platelets in the absence of the protective effects of prostacyclin. Inhibition of thromboxane synthesis effectively prevents the Paf‐induced sudden death.
Some features of the spasmogenic actions of acetylcholine and histamine in guinea‐pig isolated trachealis
Authors: Ahmed F. , Foster R.W. , Small R.C. , Weston A.H. 
Published: July 2012

Intracellular electrophysiological recording showed that acetylcholine (1 μmol l−1) and histamine (2 μmol l−1) depolarized trachealis cells and often increased the frequency of slow waves. Higher concentrations of these agents caused greater depolarization and abolition of slow waves. Marked depolarization was often associated with the appearance of electrical ‘noise’. These electrical phenomena were accompanied by tonic tension development in a contiguous segment of trachea.
Electrical ‘noise’ and tension evoked by high concentrations of acetylcholine or histamine could be dissipated by washing the agonist from the tissue. Acetylcholine‐induced ‘noise’ was resistant to tetrodotoxin (3 μmol l−1) and to hexamethonium (1 mmol l−1).
Neither acetylcholine (10–1,000 μmoll−1) nor histamine (2–200 μmol l−1) increased the lanthanum‐resistant calcium fraction of muscle‐containing strips of trachea.
It is concluded that, while developing tension under the influence of acetylcholine or histamine, trachealis cells depolarize markedly but there is relatively little cellular influx of Ca2+.
Pressure reversal of the action of octanol on postsynaptic membranes from Torpedo
Authors: Braswell L.M. , Miller K.W. , Sauter J.‐F. 
Published: July 2012

Octanol increases the binding of [3H]‐acetylcholine to the desensitized state of the nicotinic receptor in postsynaptic membranes prepared from Torpedo californica.
This increase in binding results from an increase in the affinity of [3H]‐acetylcholine for its receptor without any change in the number of sites or the shape of the acetylcholine binding curve.
High pressures of helium (300 atm) decrease [3H]‐acetylcholine binding by a mechanism that changes only the affinity of acetylcholine binding.
Helium pressure reverses the effect of octanol on the affinity of [3H]‐acetylcholine for its receptor.
This pressure reversal of the action of octanol at a postsynaptic membrane is consistent either with pressure counteracting an octanol‐induced membrane expansion or with independent mechanisms for the actions of octanol and pressure.
The data do not conform with a mechanism in which pressure displaces octanol from a binding site on the receptor protein.
Effect of nicotine on the formation of prostacyclin‐like activity and thromboxane in rabbit aorta and platelets
Authors: Alster Pawel , Wennmalm Åke 
Published: July 2012

The effect of nicotine on the bioformation of prostacyclin (PGI2) and of thromboxane (Tx)B2 in rabbit aorta and platelets, respectively, was investigated.
Rabbit aortic rings were incubated with [14C]‐arachidonic acid ([14C]‐AA) and the incubation products were separated with thin layer chromatography (t.l.c). Alternatively, the aortic rings were incubated without substrate and their spontaneous formation of platelet anti‐aggregatory activity was measured. Rabbit platelet microsomes were incubated with [14C]‐AA and the products formed were separated with t.l.c.
Rings of aorta were found to be incapable of converting added [14C]‐AA to labelled 6‐keto‐PGF1α (the stable hydrolysis product of PGI2). Rings of aorta incubated in saline medium spontaneously formed PGI2‐like activity. This formation was dose‐dependently inhibited by nicotine, with an I50 of about 10−4 m.
Platelet microsomes converted [14C]‐AA to labelled TxB2. This formation was unaffected by nicotine.
It is concluded that a true difference in sensitivity to nicotine exists between cyclo‐oxygenase in rabbit aorta and platelets. The data also demonstrate a tissue difference between rabbit aorta and platelets concerning their utilization of exogenous AA as substrate in the formation of platelet active compounds.
Mammalian platelet adrenoceptors
Authors: Kerry R. , Scrutton M.C. , Wallis R.B. 
Published: July 2012

Mammalian platelets vary widely in their responses to catecholamines in part because these agonists can act via excitatory α‐ and inhibitory β‐adrenoceptors. In the absence of antagonists, adrenaline enhances the response of rabbit platelets to an excitatory agonist, e.g. adenosine‐5′‐O‐(1‐thiodiphosphate) (ADP‐α‐s) acting at another receptor, but has no effect on the response of rat or guinea pig platelets to such an agonist. In the presence of a β‐adrenoceptor antagonist, adrenaline enhances the response of rat, but not guinea‐pig platelets to ADP‐α‐S and the extent of the enhanced effect on rabbit platelets is increased. In the presence of an α‐adrenoceptor antagonist, adrenaline inhibits the response of rabbit and rat platelets to ADP‐α‐S but has no such effect on the response of guinea‐pig platelets.
Studies using selective agonists and antagonists demonstrate that the excitatory response of rat platelets to adrenaline is mediated by an α2‐adrenoceptor, and the inhibitory response of rabbit platelets to adrenaline by a β2‐adrenoceptor as is the case in other species which have been examined.
The mean α2‐adrenoceptor density on human, rabbit, rat and guinea‐pig platelets as assessed using [3H]‐yohimbine as radioligand is obtained as 258, 270, 42 and < 10 receptors per platelet.
The mean β2‐adrenoceptor density on human, rabbit, rat and guinea‐pig platelets as assessed using (‐)‐[125I]‐iodocyanopindolol is obtained as 66, 14, 41 and < 5 receptors per platelet.
The nature of the effect of adrenaline on the response of mammalian platelets to other excitatory agonists, e.g. ADP‐α‐S, appears therefore to be largely determined by the absolute number of α2‐adrenoceptors and by the relative content of α2‐ and β2‐adrenoceptors on these cells for the species which have been examined in this analysis.
Capsaicin inhalation in man and the effects of sodium cromoglycate
Authors: Collier J.G. , Fuller R.W. 
Published: July 2012

The inhalation of capsaicin for 1 min, delivered as an aerosol by nebulising solutions of capsaicin at concentrations of 2–65 μmol l−1, caused dose‐dependent coughing in normal volunteers and subjects with mild asthma. Capsaicin did not cause a feeling of breathlessness, and had no effect on forced expiratory volume in 1 s (FEV1) measured at the 1st, 5th and 9th min after the challenge was completed.
Coughing started within seconds of applying the face mask, continued throughout the minute of capsaicin inhalation, and stopped within seconds of the mask being removed. In any one subject the number of coughs was reproducible when repeated on the same day or after an interval of several days.
Experiments using local anaesthesia applied to the buccal mucosa or larynx indicated that the cough was caused by the stimulation of capsaicin‐sensitive nerve terminals situated in the larynx.
Cough response was not altered by the prior inhalation of sodium cromoglycate.