bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H2‐agents
Authors: Andersson Per , Bergstrand Håkan 
Published: July 2012

Guinea‐pigs were sensitized to ovalbumin (OA) by immunization regimens chosen to cause antigen‐induced bronchial anaphylactic responses mediated mainly either by IgE‐like antibodies or by IgG1‐like antibodies.
Treatment of the IgE‐producing animals for three weeks with the histamine H2‐receptor antagonist cimetidine (1 mg kg−1 i.p. once a day) or with the H2‐agonist dimaprit (0.1, 1.0, or 10 mg kg−1 i.p. once a day) led to a significantly reduced bronchial response capacity compared with that of the saline‐treated controls challenged intravenously with antigen one week after the end of treatment. The changes were biphasic and not strictly dose‐dependent. In contrast, acute treatment of immunized animals with a single dose of cimetidine (10 or 30 mg kg−1 i.v.) or dimaprit (1 or 10 mg kg−1 i.v.) 2 min before challenge with OA did not significantly affect the bronchial anaphylactic response.
However, long‐term treatment with cimetidine (10 mg kg−1) or the dimaprit analogue, S‐[4‐(N, N‐dimethylamino)‐butyl] isothiourea (SKF Compound 91488) (1 mg kg−1), which is reported not to activate H2‐receptors, had no effect on the response capacity.
Treatment with cimetidine (1 mg kg−1) or dimaprit (1 mg kg−1) did not influence the response capacity to antigen challenge in IgG1‐ type animals. Dimaprit (1 mg kg−1) did not affect the responsiveness to intravenous provocation with histamine in ‘IgE‐type’ animals. Antigen‐induced release of histamine from chopped lung tissue in vitro was not significantly affected in ‘IgE‐type’ animals treated with cimetidine (1 mg kg−1) or dimaprit (1 mg kg−1).
Treatment of immunized animals with cimetidine or dimaprit one week before and one week after a booster injection of antigen also led to reduced response capacity compared with that of saline‐treated controls. However, the serum levels of IgE‐like homocytotropic antibodies of these animals were not reduced; on the contrary, those of IgG1‐antibody were increased in dimaprit‐treated animals.
These data show that intermittent treatment with histamine H2‐agents reduces reagin‐mediated anaphylactic response capacity in vivo in actively sensitized guinea‐pigs by an as yet undefined mode of action.
Muscarinic receptor occupation and receptor activation in the guinea‐pig ileum by some acetamides related to oxotremorine
Authors: Ringdahl Björn 
Published: July 2012

The dissociation constants (KD values) and relative efficacies of seven acetamide analogues of oxotremorine, including two enantiomeric pairs, at muscarinic receptors in the guinea‐pig isolated ileum were determined. The method used involved analysis of dose‐response data before and after fractional inactivation of receptors with propylbenzilylcholine mustard.
All of the compounds studied had lower affinities than oxotremorine, but some had substantially higher relative efficacies.
Replacement of the pyrrolidine ring of N‐methyl‐N‐(4‐pyrrolidino‐2‐butynyl)acetamide(I), the parent compound in the series, by a dimethylamino or a trimethylammonium group decreased the affinity 32 and 4.5 fold, respectively, whereas the relative efficacy increased 5.7–8.3 times.
There was no correlation between relative efficacies and affinities of the compounds. The structural requirements for high affinity and high efficacy appeared to be quite different.
Inhibition of allergic and non‐allergic histamine secretion from rat peritoneal mast cells by calcium antagonists
Authors: Chand N. , Diamantis W. , Pillar J. , Sofia R.D. 
Published: July 2012

Bepridil, TMB‐8 (8‐(diethylamino)octyl 3,4,5‐trimethoxybenzoate hydrochloride),diltiazem, verapamil and nifedipine exerted concentration‐dependent inhibition of antigen and calcium ionophore A23187‐induced histamine release from rat peritoneal mast cells.
The inhibitory effects of verapamil and bepridil against calcium ionophore A23187‐induced histamine secretion were antagonized by increased Ca2+ concentrations in the extracellular medium. These observations suggest that both agents act by interfering with the influx of Ca2+ into the mast cells.
The inhibitory activities of five different Ca2+ channel blockers on allergic and non‐allergic histamine secretion from rat peritoneal mast cells varied considerably depending upon the nature of the secretagogue as well as concentration and type of Ca2+‐antagonist examined.
Synergistic interaction between histamine and ouabain on ventricular fibrillation threshold
Authors: Trzeciakowski Jerome P. 
Published: July 2012

The interaction between histamine and ouabain on the ventricular fibrillation threshold (VFT) was studied in the isolated, Langendorff‐perfused heart of the guinea‐pig.
When administered separately, histamine and ouabain each reduced the VFT in a concentration‐related manner with ED50 values of 84.3 and 250 nM, respectively.
When perfused in combination the effects of these two drugs on VFT were significantly greater than the sum of their individual contributions.
Mepyramine and cimetidine both antagonized the fibrillatory effects of the histamine‐ouabain combination. Neither antagonist affected the fibrillation concentration‐response curve for ouabain.
These results suggest that both classes of histamine receptor may participate in the histamine‐ouabain interaction.
Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells
Authors: Barry W.H. , Horowitz J.D. , Smith Thomas W. 
Published: July 2012

The negative inotropic effects of calcium channel antagonists on the myocardium were used as a standard for the definition and determination of potency of this group of drugs.
The effects of six calcium channel antagonists (verapamil, methoxyverapamil (D600), nifedipine, lidoflazine, perhexiline and diltiazem) were compared on cultured chick embryo ventricular cells.
Drug concentrations producing 50% inhibition of contractile amplitude, derived from linearized concentration‐response curves, varied from 2.8 × 10−8 M for nifedipine to 8.3 × 10−7 M for perhexiline. Equipotent negative inotropic concentrations of verapamil, D600, perhexiline, diltiazem and lidoflazine produced a similar inhibitory effect on 45Ca uptake into cultured cells. Nifedipine produced no significant inhibition of 45Ca uptake.
The time required for recovery of contractility after cessation of drug superfusion varied in the order lidoflazine > perhexiline >D600> verapamil > nifedipine > diltiazem. This relative order accords closely with the reported in vivo half‐lives of these drugs.
It is concluded that while some inhibition of 45Ca2+ uptake into cardiac cells can be demonstrated with five of the six calcium channel blockers studied, the relationship between the degree of inhibition of calcium influx and negative inotropic effects may not be uniform for all calcium channel antagonists.
Pressor sensitivity to exogenous vasopressin in conscious, adult rats treated neonatally with capsaicin
Authors: Bennett T. , Gardiner S.M. 
Published: July 2012

Pressor responses to exogenous arginine vasopressin were assessed in adult rats that had been treated neonatally with capsaicin or its vehicle. Measurements were made under control conditions, after inhibition of baroreflexes (with pentolinium), and after inhibition of baroreflexes (with pentolinium) and the production of angiotensin II (with captopril).
Resting arterial blood pressures and pressor sensitivities to exogenous arginine vasopressin were similar in capsaicin‐treated and vehicle‐injected rats.
Sixty minutes after the administration of pentolinium, systolic and diastolic blood pressures were reduced in both groups of rats and the pressor responses to arginine vasopressin were similarly and significantly enhanced.
In both groups of rats 60 min after administration of pentolinium and captopril, systolic and diastolic blood pressures were lower than in the presence of pentolinium alone, but pressor responses were not different from those seen in control conditions.
The possibility that the present results are explicable in terms of baroreflexes, the renin‐angiotensin system and endogenous vasopressin interacting to influence the pressor sensitivity to exogenous vasopressin is discussed. From the present findings, it seems that our previous observation of impaired, vasopressin‐mediated blood pressure recovery following acute hypotension in capsaicin‐treated rats cannot be attributed to a reduced pressor sensitivity to the hormone.
Comparison of the antagonistic effects of phentolamine on vasoconstrictor responses to exogenous and neurally released noradrenaline in vivo
Authors: Bell C. 
Published: July 2012

The antagonistic effects of the α‐adrenoceptor blocking agent phentolamine on vasoconstrictor responses to intraluminal noradrenaline and lumbar sympathetic nerve stimulation were compared in the hindlimb of the anaesthetized dog.
Sympathetic stimulation with 1 pulse or trains of 4–10 pulses at 0.4–40 Hz produced graded vasoconstrictor responses that were matched in amplitude by intra‐arterial injections of 10−8–10−6 g noradrenaline. Phentolamine (0.5 mg kg−1 i.v.) attenuated amplitude‐matched responses to both types of stimuli to quite similar extents.
The extent of the effect of phentolamine on neurogenic responses was greater with 1 pulse stimulation than with trains, and greater with 4 pulse than with 10 pulse trains. The effect was maximal within 2 min of phentolamine administration and wore off in parallel with that on responses to injected noradrenaline.
The results are consistent with the view that transmitter released from noradrenergic vasoconstrictor nerves acts primarily on subjunctional α‐adrenoceptors.
Quantification of the characteristics of antagonists exhibiting both competitive antagonism and functional interaction
Authors: Hughes I.E. , Mackay D. 
Published: July 2012

Null equations have been derived which, when applied to log10 concentration‐tissue state curves for an agonist determined in the presence and absence of a competitive antagonist which also exhibits functional interaction, allow quantitation of the characteristics of the competitive and functional interactant effects.
Both the affinity constant of the antagonist for its receptors and numerical values characterizing the functional interaction can be obtained.
The null equations have been tested in a model system by using a mixture of papaverine hydrochloride (either 5 or 20 μM) and methyl atropine bromide (10 nM) to mimic a competitive antagonist which also shows functional interaction.
Agreement between values derived directly and indirectly from the model is good and validates the use of the null equations.
Similarity between μ‐opioid receptors in mouse vas deferens and guinea‐pig ileum
Authors: Goodall Jacqueline , Hughes I.E. , Mackay D. 
Published: July 2012

The effects of the opioid receptor agonist RX783006 and of the opioid receptor partial agonist (+)‐meptazinol have been examined on electrically‐induced twitch responses of the guinea‐pig isolated ileum and of the mouse isolated vas deferens.
Log10 concentration‐tissue state curves were determined for (+)‐meptazinol and for RX783006, alone, in combination and, when appropriate, in the presence of naloxone (30 nM).
Analysis of these log10 concentration‐tissue state curves using the null equations derived and verified in the previous paper allows quantitation of the characteristics of the interaction of (+)‐meptazinol with the opioid receptors in these tissues.
The results indicate that the apparent differences in the actions of (+)‐meptazinol on isolated electrically‐stimulated guinea‐pig ileum and mouse vas deferens can be accounted for without the need to postulate differences between μ‐opioid receptors in these two tissues.
Cellular uptake disguises action of L‐glutamate on N‐methyl‐D‐aspartate receptors: With an appendix: Diffusion of transported amino acids into brain slices
Authors: Garthwaite J. 
Published: July 2012

Pharmacological properties of the guanosine 3′5′‐cyclic monophosphate (cyclic GMP) responses to excitatory amino acids and their analogues were compared in slices and dissociated cells from the developing rat cerebellum maintained in vitro. The intention was to determine the extent to which cellular uptake might influence the apparent properties of receptor‐mediated actions of these compounds.
In slices, the potencies of the weakly (or non‐) transported analogues, N‐methyl‐D‐aspartate (NMDA) and kainate (KA) (EC50 = 40 μM each) were higher than those of the transported amino acids, D‐ and L‐aspartate (EC50 = 250 μM and 300 μM) and D‐ and L‐glutamate (EC50 = 540 μM and 480 μM). Quisqualate (up to 300 μM) failed to increase cyclic GMP levels significantly. The sensitivity of agonist responses to the NMDA receptor antagonist, DL‐2‐amino‐5‐phosphonovalerate (APV), was in the order NMDA > L‐aspartate > L‐glutamate, KA.
In dissociated cells, L‐glutamate was 280 fold more potent (calculated EC50 = 1.7 μM). L‐ and D‐aspartate (calculated EC50 = 13 μM) and D‐glutamate (EC50 = 130 μM) were also more effective than in slices. The potencies of NMDA and KA were essentially unchanged. Responses to NMDA, L‐glutamate and L‐aspartate under these conditions were equally sensitive to inhibition by APV but the response to KA remained relatively resistant to this antagonist.
The implications of these results are that, in slices, cellular uptake is responsible for (i) the dose‐ response curves to L‐glutamate, L‐ and D‐aspartate bearing little or no relationship to the true (or relative) potencies of these amino acids; (ii) the potency of APV towards the actions of transported agonists acting at NMDA receptors being reduced and (iii) a differential sensitivity to APV of responses to L‐glutamate and L‐aspartate being created, the consequence being that a potent action of L‐glutamate on NMDA receptors is disguised.
These conclusions are supported by theoretical considerations relating to the diffusion of transported amino acids into brain slices, as elaborated in the Appendix.
Different responsiveness of prostaglandin D2‐sensitive systems to prostaglandin D2 and its analogues
Authors: Narumiya Shuh , Toda Noboru 
Published: July 2012

Prostaglandin D2 (PGD2) and six PGD2 analogues were used to classify responsiveness of several PGD2‐sensitive systems. The analogues used were 9β‐PGD2, 5‐(6‐carboxyhexyl)‐1‐(3‐cyclohexyl‐3‐hydroxypropyl)hydantoin (BW245C), 17‐phenyl‐18,19,20‐trinor‐PGD2 (17‐phenyl‐PGD2), PGD2 amide, PGD2 N‐monomethylamide and 11‐keto‐15α‐hydroxy‐δ5,9,12‐prostenoic acid (9‐deoxy‐δ9,12‐PGD2). The PGD2‐sensitive systems examined were human platelets, rat peritoneal mast cells, rabbit transverse stomach strip, guinea‐pig tracheal ring chain and helical strip of the dog cerebral artery.
PGD2, 9β‐PGD2 and BW245C inhibited the aggregation of human platelets, increased adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) in rat mast cells and relaxed the rabbit stomach strip. The rank order of potency was BW245C>PGD2>9β‐PGD2. PGD2 amide and PGD2 N‐monomethylamide were inactive in the former two systems but elicited relaxant activity on the rabbit stomach strip. 17‐Phenyl‐PGD2 was virtually inactive in the above three systems.
PGD2 and 17‐phenyl‐PGD2 contracted the guinea‐pig tracheal ring chain and the helical strip of dog cerebral arteries with almost equal potency. 9β‐PGD2 and BW245C antagonized competitively the contractile action of PGD2. PGD2 amide and PGD2 N‐monomethylamide showed weak agonistic actions in the tracheal preparation.
9‐Deoxy‐δ9,12‐PGD2, showing stronger growth inhibition than PGD2 on cultured tumour cells, was inactive in human platelets, rat mast cells and guinea‐pig trachea, and elicited contractile response in the rabbit stomach strip.
These results indicate the presence of three groups of PGD2‐sensitive systems that respond differently to PGD2 and its analogues.
The properties of the clonidine withdrawal response of guinea‐pig isolated ileum
Authors: Chahl Loris A. 
Published: July 2012

The dependence‐inducing effects of clonidine were investigated on the guinea‐pig isolated ileum. Clonidine produced relaxation of the ileum with a threshold concentration between 0.01 and 0.1 μmol 1−1. Washout of clonidine did not induce a withdrawal contraction.
Following 2 min contact of the ileum with clonidine, 1 μmol 1−1, addition of phentolamine, 5 μmol 1−1, induced a contracture. The phentolamine‐precipitated withdrawal contracture did not increase in height with a longer period of contact (32 min) of the ileum with clonidine.
The phentolamine‐precipitated withdrawal contracture following 2 min contact of ileum with clonidine was abolished by atropine, 5 μmol 1−1, and substance P (SP) antagonists, (D‐Pro2, D‐Phe7, D‐Trp9)‐SP and spantide, 10 μmol 1−1.
[Met5]enkephalin, 1 μmol 1−1, abolished the withdrawal response to clonidine and clonidine, 1 μmol 1−1, abolished the withdrawal response to [Met5]enkephalin.
Following 2 min contact of the ileum with noradrenaline, 5 μmol 1−1, washout or addition of phentolamine or yohimbine, 5 μmol 1−1, also induced a withdrawal response. The noradrenaline washout withdrawal response was abolished by atropine, 5 μmol 1−1, and spantide, 10 μmol 1−1.
Since clonidine dependence may be induced as rapidly as opiate dependence in the ileum and the pharmacology of the withdrawal responses is similar, it is suggested that they both induce the same post‐receptor neuronal feedback disturbance in which substance P neurones play a major role.
Stimulation rate modulates effects of the dihydropyridine CGP 28 392 on cardiac calcium‐dependent action potentials
Authors: Kamp Timothy J. , Miller Richard J. , Sanguinetti Michael C. 
Published: July 2012

Calcium (Ca2+)‐dependent action potentials were recorded from 22 mM potassium (K+)‐depolarized guinea‐pig papillary muscle at several different pacing frequencies in the absence and presence of CGP 28 392 (10 μM), a Ca2+ channel agonist. The maximum upstroke velocity (max) of the slow response action potential was measured to determine relative changes in Ca2+ current as a function of pacing frequency.
CGP 28 392 increased max more than two fold at low rates of stimulation (1 or 12 pulses min−1), but had no significant effect on max during rapid pulsing (200 pulses min−1).
The enhancement of max was dependent upon extracellular [K+]. Increasing extracellular [K+] from 22 mM to 27 mM suppressed the frequency‐dependent agonist effects and increased the antagonist effects on max.
These results indicate that CGP 28 392 is a partial Ca2+‐channel agonist and suggest that its effects on Ca2+ current are voltage‐dependent.
A pharmacological study on respiratory rhythm in the isolated brainstem‐spinal cord preparation of the newborn rat
Authors: Murakoshi Takayuki , Suzue Toshihiko , Tamai Sunao 
Published: July 2012

An in vitro brainstem‐spinal cord preparation of the newborn rat was used to examine the effects of neurotransmitters and transmitter candidates on respiratory frequency.
Spontaneous periodic depolarization of the spinal ventral roots of the 4th or 5th cervical segment was observed at a frequency of 5–15 min−1 constantly for more than 5 h. The frequency of this depolarization was monitored as an index of the respiratory frequency.
An elevation of the concentration of Ca2+ or Mg2+ caused a decrease in the respiratory frequency, whereas an elevation of K+ concentration caused an increase. The frequency was also increased by a reduction of pH. The highest frequency was observed at 27–28°C.
Dopamine, 5‐hydroxytryptamine, histamine, acetylcholine, glutamic acid, substance P, and thyrotropin releasing hormone accelerated the respiratory frequency when applied by perfusion to the brainstem, whereas noradrenaline, γ‐aminobutyric acid, glycine, and [Met5] enkephalin and [Leu5] enkephalin slowed the frequency. Experiments with antagonists suggested that the stimulant effect of acetylcholine on respiratory frequency was mediated mainly by muscarinic receptors and the depressant effect of noradrenaline was mediated by α‐adrenoceptors.
TI‐233 as a glutamate channel blocker at the crayfish neuromuscular junction
Authors: Ishida M. , Shinozaki H. 
Published: July 2012

Effects of TI‐233 (4‐isopropyl‐1‐[N2‐(5,6‐dimethyl‐aminonaphthalene‐1‐sulphonyl)‐L‐arginyl]‐piperidine) on glutamate‐induced responses and nerve‐evoked synaptic responses were compared at the crayfish neuromuscular junction.
Intracellularly recorded excitatory junctional potentials (e.j.ps) were markedly augmented by TI‐ 233 when they were evoked at long intervals, whereas the unit size of extracellular e.j.ps was hardly affected by TI‐233 and, at that stage, the glutamate‐induced current was markedly reduced by TI‐233.
The decay rate of extracellular e.j.ps was slightly increased 3 min after the addition of TI‐233 at concentrations higher than 0.05 mM.
Repetitive stimulation of the excitatory axon at a high frequency caused a gradual decrease in the amplitudes of extracellular e.j.ps in the presence of TI‐233. After prolonged application of TI‐233 with repetitive nerve stimulation, the glutamate‐induced response became significantly smaller than the control.
TI‐233 increased the input resistance of the crayfish muscle fibre and facilitated transmitter release at the excitatory neuromuscular junction. These two effects would entirely explain the augmentation of intracellular e.j.ps by TI‐233.
TI‐233 (> 3 μM) reduced the amplitude of current responses to trains of glutamate pulses in a dose‐dependent manner, but this reduction by TI‐233 was time‐ and activity‐dependent. The effect of TI‐233 on glutamate‐induced responses was voltage‐dependent and hyperpolarization increased this effect.
Pretreatment of the muscle fibre with concanavalin A did not affect the gradual decline, caused by TI‐233, of the successive currents evoked by a train of glutamate pulses.
The apparent differences between the glutamate‐induced current and nerve‐evoked synaptic response revealed by TI‐233 can be explained by open‐channel block of the glutamate‐activated ion‐ channel, and do not confute the hypothesis that glutamate is the natural transmitter substance at this junction.