bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat
Authors: Curtis M.J. , MacLeod B.A. , Walker M.J.A. 
Published: July 2012

The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats.
Verapamil (2–20 mg kg−1, i.v. given pre‐occlusion) dose‐dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg−1. This dose was effective when given immediately post‐occlusion.
Severe arrhythmias, as opposed to PVC, were preferentially reduced.
In conscious, and pentobarbitone‐anaesthetized rats, verapamil (6 mg kg−1) had different effects on electrically‐induced arrhythmias, and the ECG, from an equi‐effective anti‐arrhythmic dose of quinidine (20 mg kg−1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P‐R interval, but only quinidine increased QRS and Q‐T intervals.
Thirty minutes post‐occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg−1 dose given pre‐ or post‐occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 ± 0.8 μmol l−1 and 0.6 ± 0.1 μmol l−1 (x̄ ± s.e.mean), respectively following post‐occlusion administration vs. 2.7 ± 1.2 and 0.24 ± 0.04 for pre‐occlusion administration.
Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+
We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug.
Aliphatic alcohols increase the decay rate of glutamate‐activated currents at the crayfish neuromuscular junction
Authors: Wachtel Ruth E. 
Published: July 2012

Excitatory junction currents produced by glutamate were recorded with an extracellular electrode at the excitatory neuromuscular junction of the crayfish.
The currents decayed more quickly as the membrane was hyperpolarized. The direction of the voltage sensitivity of the decay phase is thus opposite to that found for acetylcholine‐activated currents at the amphibian endplate.
The aliphatic alcohols ethanol to octanol all increased the rate of decay of the currents. The effects of the short chain alcohols were opposite to their actions at the toad endplate, where ethanol to pentanol prolong the currents. This observation was explained in terms of the opposite direction of the voltage sensitivity in the two preparations.
For each alcohol, the relationship between the half‐decay time of the currents (t1/2) and alcohol concentration was exponential.
The potency of each alcohol in decreasing t1/2 was exponentially related to carbon chain length, which would be predicted if the effects of the alcohols were directly related to their concentration in the lipid phase of the membrane.
These findings are consistent with the ideas that the alcohols may alter membrane polarizability or change membrane fluidity in the vicinity of the channels.
Further evidence for the existence of two receptor sites for bradykinin responsible for the diphasic effect in the rat isolated duodenum
Authors: Boschcov Paulo , Paiva Antonio C.M. , Paiva Therezinha B. , Shimuta Suma I. 
Published: July 2012

Low doses of bradykinin (below 10 nM), as well as of K+ (below 10 mM) induced relaxation, whereas higher doses caused contraction of the rat duodenum.
The relaxant responses induced by bradykinin and K+ were not affected by ouabain (1 μM), but pre‐incubation with 5.9 mM K+ abolished the responses to that ion but not those to bradykinin.
The contractile and relaxant components of the response to bradykinin (but not those to K+) increased with the time elapsed after mounting of the preparation, and this was due to stretching by the load of the recording system.
Specific and reversible desensitization (tachyphylaxis) was observed with the contractile response (but not the relaxation) induced by bradykinin.
Des‐Arg9‐bradykinin, an analogue specific for B1‐receptors, was much less active than bradykinin, and elicited only a contractile response.
Among four bradykinin potentiating peptides that were tested, potentiator C enhanced the relaxation only, whereas BPP5a and captopril potentiated only the contraction and BPP9a potentiated both types of response to bradykinin.
Our results support the hypothesis that the relaxant and contractile components of the rat duodenum's response to bradykinin are due to actions at different receptor sites, which can be distinguished by their properties (desensitization) and their different apparent affinities for agonists and for potentiating peptides.
The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat
Authors: Curtis M.J. , Macleod B.A. , Walker M.J.A. 
Published: July 2012

The role of the central nervous system (CNS) in arrhythmogenesis in the 4 h period following occlusion of a coronary artery was investigated in rats by use of CNS ablations and other procedures.
Ablations in the CNS included pithing, spinalization and decerebration combined with acute and chronic surgical preparation and noradrenaline/adrenaline infusions.
All procedures involving acute surgery reduced the incidence and severity of the arrhythmias induced by occlusion. Such reductions were most marked in the second (0.5‐4 h post‐occlusion) arrhythmic period.
The observed reductions in arrhythmias could not be explained in terms of involvement of the CNS or adrenoceptor activation.
When circulating leucocytes, platelets and serum potassium were measured in a group of pithed rats before and after occlusion, reduced levels (20–50%) of both leucocytes and platelets occurred while serum potassium levels rose by 50–100%.
Arrhythmias following coronary occlusion may depend in part on factors in the blood such as leucocytes, platelets and serum potassium and these factors may be altered by acute surgery.
Effects of indomethacin, piroxicam and selected prostanoids on gastric acid secretion by the rat isolated gastric mucosa
Authors: Reeves J.J. , Stables R. 
Published: July 2012

The effects of the cyclo‐oxygenase inhibitors indomethacin and piroxicam have been investigated on histamine‐ and dibutyryl cyclic AMP‐induced acid secretion in the rat isolated gastric mucosa. The relative potencies of a number of prostanoids as inhibitors of histamine‐induced acid secretion were determined in an attempt to classify the prostaglandin receptor mediating this response.
Indomethacin (8 × 10−9 − 2.7 × 10−6 M) and piroxicam (3 × 10−6 M) potentiated the secretory responses elicited by histamine. This effect might be due to inhibition of the biosynthesis of antisecretory prostanoids. Indomethacin (2.7 × 10−6 M) and piroxicam (3 × 10−6 M) also potentiated the secretory response to dibutyryl cyclic AMP, but since prostaglandin E2 (PGE2, 10−5M) did not inhibit this secretory response, the mechanism of the potentiation may differ from that of histamine.
The potency of the thromboxane mimetic U‐46619 as an inhibitor of histamine‐induced acid secretion was markedly reduced in the presence of indomethacin, suggesting that U‐46619 may release endogenous antisecretory prostanoids.
In the presence of indomethacin (2.7 × 10−6 M) all the prostanoids tested produced concentration‐related inhibitions of histamine‐induced gastric acid secretion. PGE‐analogues were the most potent compounds, the rank order of potency being 16, 16 dimethyl PGE2 > PGE2 > PGF2α > U‐46619 > PGD2 > PGI2. This order of potency is very similar to that obtained in smooth muscle preparations containing ‘EP’ receptors, suggesting that this receptor type also mediates inhibition of histamine‐induced acid secretion in the rat.
The effect of a calcium antagonist, nitrendipine, on the responses of isolated strips of human, chorionic plate artery to prostaglandins E2 and E1
Authors: Pipkin F. Broughton , Chinnery E. 
Published: July 2012

Six point concentration‐response curves were established for the contractile effect of prostaglandin E2 (PGE2) on helically‐cut strips of human chorionic plate arteries.
Tissues were then allocated to one of four treatment groups: a control group and 3 groups exposed to the calcium channel blocker nitrendipine at 10−9, 10−7 or 10−5 M. The concentration‐response curves were then repeated.
The addition of nitrendipine was associated with a significant depression of the induced contraction. The contractile response to the lower doses of PGE2 was replaced by a small relaxation in 63% of the treated tissues.
It is suggested that in these tissues PGE2 exerts its constrictor effect via the receptor‐operated channels and that nitrendipine is blocking this effect.
Similar experiments performed with PGE1 showed great variability in the initial response. Nitrendipine 10−5 M failed to exert any detectable effect on this response.
Pregnancy‐induced hypertension is associated with vasoconstriction in both the maternal and placental circulations. There also appears to be a relative excess of vasoconstrictor eicosanoid production. Nitrendipine may be of use in the treatment of this condition.
Cl−/Ca2+‐dependent L‐glutamate binding sites do not correspond to 2‐amino‐4‐phosphonobutanoate‐sensitive excitatory amino acid receptors
Authors: Fagg Graham E. , Lanthorn Thomas H. 
Published: July 2012

A series of phosphono and phosphino analogues of glutamate were used to compare the pharmacological properties of (a) Cl−/Ca2+‐dependent, 2‐amino‐4‐phosphonobutanoate (AP4)‐sensitive L‐[3H]‐glutamate binding sites in rat brain synaptic plasma membranes (SPMs) and (b) AP4‐sensitive excitatory synaptic responses by use of electrophysiological techniques.
In the presence of Cl− and Ca2+, L‐[3H]‐glutamate bound to SPMs with Kd804 nM and Bmax 53 pmol mg−1 protein. The AP4‐sensitive (Ki 7.3 μM) population of binding sites represented 61 % of L‐glutamate specifically bound. co‐Substituted analogues of AP4 were potent inhibitors of L‐[3H]‐glutamate binding (Ki values 2.4–38 μM), whereas N‐substituted compounds or propionic acid derivatives were inactive. Experiments with AP4 alone and in combination with other analogues demonstrated that the primary target of all substances was the AP4‐sensitive population of L‐glutamate binding sites.
In the hippocampal slice in vitro, AP4 antagonized lateral perforant path‐evoked field potentials with an IC50 of 2.7 μM. In contrast to their actions at AP4‐sensitive L‐glutamate binding sites, all other compounds (except for the ω‐carboxymethylphosphino analogue, IC50 19 μM) were weak or inactive as antagonists of this synaptic response (IC50 values > 100 μM). Inactive compounds which exhibited activity in the binding assay did not reverse the synaptic depressant effects of AP4, indicating that they were neither agonists nor antagonists at AP4‐sensitive synapses.
The lack of correspondence between (a) the Cl−/Ca2+‐dependent, AP4‐sensitive population of L‐[3H]‐glutamate binding sites and (b) AP4‐sensitive synaptic responses indicates that these binding sites are not the receptors through which AP4 exerts its neuropharmacological effects. The possibility that Cl−/Ca2+‐dependent ‘binding sites’ represent transport into resealed SPM vesicles is discussed.
Electrophysiological data demonstrate that AP4‐sensitive synaptic receptors display a high degree of ligand selectivity. High antagonist potency is shown only by glutamate analogues with unmodified α‐amino and α‐carboxyl groups, and with a bifunctional (dianionic) ω‐terminal.
Increased total activity in the rat after L‐tryptophan plus the monoamine oxidase‐A inhibitor amiflamine but not after L‐tryptophan plus clorgyline
Authors: Archer T. , Fowler C.J. , Fredriksson A. , Lewander T. , Magnusson O. , Mohringe Bodil , Söderberg U. 
Published: July 2012

The effect of pretreatment with either saline or the monoamine oxidase‐A inhibitors clorgyline and amiflamine upon the total activity, locomotion and rearing behaviour of the rat induced by various doses of the monoamine precursor L‐tryptophan was studied by use of automated activity boxes.
Amiflamine (2.5 and 5.0 mg kg−1, i.p.) increased in a dose‐dependent manner total activity and to a lesser extent, locomotion when given 60 min before L‐tryptophan (100 mg kg−1, i.p.). The increased activity was seen after amiflamine plus either 25 or 75 mg kg−1 L‐tryptophan. Rearing behaviour was not affected.
Analysis of 5‐hydroxytryptamine (5‐HT) and its deaminated metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) by high performance liquid chromatography with electrochemical detection indicated that in both frontal cortex and hypothalamus, amiflamine (at both doses) increased 5‐HT and reduced 5‐HIAA concentrations. Combination of amiflamine with L‐tryptophan (100 mg kg−1, i.p.) resulted in a higher 5‐HT concentration being found than after amiflamine alone. L‐Tryptophan treatment alone did not change 5‐HT concentrations but increased 5‐HIAA concentrations.
Clorgyline, at a dose of either 1 or 5 mg kg−1 i.p. plus L‐tryptophan (25 or 100 mg kg−1, i.p.) did not increase total activity, locomotion or behaviour.
A number of possible explanations for the differences in the behavioural effects of clorgyline and amiflamine when given with L‐tryptophan are discussed. It is concluded that in addition to monoamine oxidase‐A inhibition, other pharmacological effects of the drugs, such as 5‐HT release (amiflamine) and inhibition of tryptophan hydroxylation (clorgyline) may be of importance in determining the magnitude of the increase in activity when the compounds are given together with L‐tryptophan.
Reactivity to bradykinin and potassium of the isolated duodenum from rats with genetic and renal hypertension
Authors: Miasiro Nobuco , Paiva Therezinha B. , Pereira Claudia C. , Shimuta Suma I. 
Published: July 2012

The biphasic (relaxation‐contraction) response of the isolated duodenum was used to study the reactivity of non‐vascular smooth muscles in genetic (SHR) and renal hypertensive rats compared to their respective controls (WKY and Wistar).
For the contractile component of the response to bradykinin, the duodenum from WKY rats was more sensitive, whereas the duodenum from SHR was both more sensitive and hyperreactive, compared to that from Wistar rats.
The relaxant component of the response to bradykinin was present in the duodenum of both WKY rats and SHR, but was concentration‐dependent only in the WKY group.
The relaxant response to K+ was very small in SHR, and was not concentration‐dependent.
The concentration‐response curves for relaxant responses to adrenaline and for contractile responses to acetylcholine did not differ in the SHR and WKY groups.
Ca2+/Mg2+‐ATPase activity was found to be markedly reduced in the SHR group.
No qualitative or quantitative differences were observed between the responses of the duodenum of renal hypertensive rats and those of their normotensive controls.
It is proposed that the altered reactivity of the SHR duodenum is due to changes in ion handling by the smooth muscle cell membrane.
Characterization of [3H]‐nitrendipine binding to uterine smooth muscle plasma membrane and its relevance to inhibition of calcium entry
Authors: Batra S. 
Published: July 2012

Specific, high affinity (KD = 164 pM) binding of the Ca channel inhibitor [3H]‐nitrendipine was identified in plasma membrane‐enriched fractions from the rat myometrium.
Although dihydropyridines effectively competed for [3H]‐nitrendipine binding sites, both verapamil and D600 were poor competitors. Diltiazem (10 μM) increased [3H]‐nitrendipine binding by about 40%, but had no effect on binding affinity. Among several other drugs tested, diethylstilboestrol (DES) caused a considerable inhibition of binding, with an IC50 value of 4 μM.
Both La3+ and EDTA (or EGTA) inhibited binding. The inhibition by the latter could be overcome by the addition of Ca2+ or Mg2+.
A clear relationship was found between [3H]‐nitrendipine binding and 5′‐nucleotidase activity in the various subcellular fractions.
Data on K+‐stimulated Ca2+ influx in the intact uterine strips showed a good agreement between the inhibition by both nitrendipine and DES of stimulated Ca influx and their inhibitory effect on [3H]‐nitrendipine binding to plasma membrane. This type of correlation was lacking in the case of D600.
These results suggest that Ca channels in the myometrial membrane possess multiple sites at which different drugs can act to block these channels.
Immediate hypersensitivity reactions in epithelia from rats infected with Nippostrongylus brasiliensis
Authors: Baird A.W. , Cuthbert A.W. , Pearce F.L. 
Published: July 2012

Colonic epithelia from rats infected with the nematode Nippostrongylus brasiliensis have been studied under short circuit conditions and in response to challenge with worm antigen.
Challenge from the serosal but not the mucosal side with antigen caused a transient increase in inwardly directed short circuit current. No effects were observed in comparable tissues from non‐infected animals.
Simultaneous measurements of short circuit current and of the fluxes of sodium or chloride ions showed there was an increase in electrogenic chloride secretion and an inhibition of electroneutral sodium chloride absorption, associated with antigen challenge. This result, together with the inhibitory effects of piretanide on the response to antigen challenge, indicate that chloride ions are a major carrier of the short circuit current response. However, the equivalence of the biophysical response to ion fluxes was not established, there being an excess of chloride secretion.
The mast cell stabilizing agent, FPL 52694, significantly inhibited the current responses to antigen, while cromoglycate and doxantrazole were ineffective. Mepyramine, an H1‐receptor antagonist, and indomethacin, an inhibitor of fatty acid cyclo‐oxygenase, were without effect on the responses to antigen challenge.
Anti‐rat IgE produced qualitatively similar responses to antigen in both normal and sensitized colonic epithelia. However, the responses were significantly greater in tissues derived from infected animals. Maximally effective antigen concentrations prevented subsequent responses to anti‐rat IgE in sensitized tissues, while anti‐rat IgE only attenuated the responses to antigen.
The ways in which antigen challenge modifies epithelial function is discussed, particularly in relation to its possible role in promoting rejection of the nematodes during secondary infection.A reprint similar to this one, in which the nematode Trichinella spiralis was used, has appeared recently (Russell & Castro, 1985).
Inhibition of ionophore‐stimulated leukotriene B4 production in human leucocytes by monohydroxy fatty acids
Authors: Camp R.D.R. , Fincham N.J. 
Published: July 2012

Leukotriene B4 (LTB4) release by calcium ionophore‐stimulated human leucocytes was measured by use of selective solvent partition of reaction mixtures and an agarose microdroplet chemokinesis assay, and the inhibitory effects of four monohydroxy fatty acids were determined.
15‐Hydroxy‐eicosatetraenoic acid (15‐HETE) was the most effective inhibitor of LTB4 production with an approximate IC50 value of 6 μM and 99% inhibition at 50 μM, whereas 13‐hydroxyoctadecadienoic acid (13‐HODD) and 12‐HETE were weaker inhibitors with approximate IC50 values of 32 μM and 23 μM, and 59% and 68% inhibition at 50 μM, respectively.
We suggest that 13‐HODD and 12‐HETE, which are present in large amounts in the lesions of the skin disease psoriasis, may act as endogenous modulators of 5‐lipoxygenase activity in skin.
The effects of drugs acting at the GABAA‐receptor/ionophore after chemical kindling with the benzodiazepine receptor ligand FG 7142
Authors: Little H.J. , Nutt D.J. , Taylor S.C. 
Published: July 2012

Repeated administration of the β‐carboline benzodiazepine receptor ligand FG 7142 produces sensitization to its effects so that full seizures develop (chemical kindling); initially it is only proconvulsant. The present study investigated alterations in the function of drugs which act at the different sites at the γ‐aminobutyric acid (GABA) benzodiazepine receptor complex, after repeated administration of FG 7142.
In FG 7142 kindled mice decreased anticonvulsant and hypothermic effects of the GABA agonist muscimol were observed. The hypothermic effects of the GABA agonist progabide were reduced. In contrast a small increase in the hypothermic effect of pentobarbitone was seen.
The convulsant effects of bicuculline and picrotoxin were unaltered when they were given intravenously but marginally increased when they were given by the intraperitoneal route. No changes were seen in the hypothermic effects of these drugs.
No significant changes were seen in the convulsant or hypothermic effects of pentylenetetrazol.
These results suggest that kindling with FG 7142 may alter GABA receptor function.
Impromidine is a partial histamine H2‐receptor agonist on human ventricular myocardium
Authors: English T.A.H. , Gristwood R.W. , Owen D.A.A. , Wallwork J. 
Published: July 2012

The inotropic effects of impromidine have been studied and compared with those of histamine on human isolated left ventricular preparations stimulated at 1 Hz. Both drugs caused concentration‐related increases in force of contraction and were of similar potency, although the maximum response to impromidine was markedly and significantly less than that to histamine.
The positive inotropic responses of impromidine were inhibited by cimetidine 1 × 10−5 M, consistent with histamine H2‐receptor involvement.
Impromidine 1 × 10−4 M inhibited maximal responses to histamine to a level equal to the maximal impromidine response; however, impromidine did not inhibit responses to isoprenaline.
Positive inotropic activity and inhibition of maximal responses to histamine occurred over a similar impromidine concentration‐range.
Impromidine displaced histamine concentration‐response curves to the right, whereas mepyramine had no effect on responses to histamine.
It is concluded that impromidine has positive inotropic activity on the human ventricle, that the response is mediated via histamine H2‐receptors, and that impromidine is a partial agonist compared with histamine.
Receptor‐responses in fresh human ciliary muscle
Authors: Lograno Marcello D. , Reibaldi Alfredo 
Published: July 2012

The physiological and pharmacological properties of ciliary muscle isolated from fresh human eyes were investigated.
The muscle exhibited no spontaneous activity. Concentration‐dependent contractions in response to carbachol were competitively antagonized by atropine (pA2 = 8.95).
The muscle, precontracted by carbachol (2.7 × 10−4 M), responded to the application of isoprenaline by concentration‐dependent relaxation blocked by propranolol (3.5 × 10−9 M to 3.5 × 10−8 M; pA2 = 9.15).
Angiotensin‐evoked contractions were antagonized by 8‐Ala‐angiotensin II (4.5 × 10−8 M) in a competitive manner, but were not inhibited by phentolamine or propranolol.
Contractions generated by electrical stimulation of the muscle (30 ms, 20 Hz, 60 pulses) were antagonized by atropine (10−7 M) and tetrodotoxin (6.3 × 10−7 M). Phentolamine and propranolol did not influence these responses.
An increase of the external potassium concentration ([K+]o) from 5.4 to 158.8 mM produced a mechanical response, antagonized by atropine, but not influenced by tetrodotoxin, phentolamine or propranolol.
The human ciliary muscle appears to carry muscarinic and angiotensin receptors and β2‐adrenoceptors. The estimate of Katropine for muscarinic receptors mediating carbachol‐induced contractions agrees with estimates of Katropine reported for human and rabbit iris.