bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE LOCAL ANTINOCICEPTIVE AND TOPICAL ANTI‐INFLAMMATORY EFFECTS OF PROPYL GALLATE IN RODENTS
Authors: McDONALD‐GIBSON WENDY J. , SAEED S.A. , SCHNEIDER C. 
Published: July 2012

In common with several anti‐inflammatory, analgesic, local anaesthetic and antioxidant drugs, propyl gallate in vitro inhibited the biosynthesis of prostaglandin E2 and F2α from arachidonic acid by a prostaglandin synthetase from bull seminal vesicles.
In common with analgesic drugs, propyl gallate reduced the ability of arachidonic acid, acetylcholine or acetic acid to cause abdominal constrictions in mice.
Using a new method of evaluating anti‐inflammatory activity, we demonstrated the effectiveness of aspirin or indomethacin given subcutaneously before u.v. irradiation of guinea‐pig ears, the prophylactic action of topically applied sunscreen agents and the therapeutic value of bufexamac and propyl gallate applied after irradiation.
CENTRALLY INDUCED HYPOTENSION AND BRADYCARDIA AFTER ADMINISTRATION OF α‐METHYLNORADRENALINE INTO THE AREA OF THE NUCLEUS TRACTUS SOLITARII OF THE RAT
Authors: DE JONG W. , NIJKAMP F.P. 
Published: July 2012

In anaesthetized rats, bilateral injections of α‐methylnoradrenaline, noradrenaline or adrenaline into the area of the nucleus tractus solitarii (NTS) of the brain stem caused dose‐dependent decreases of systemic arterial blood pressure and heart rate. The effects of α‐methylnoradrenaline were most pronounced and lasted longest.
The cardiovascular effects of α‐methylnoradrenaline appeared to be restricted to the medio‐caudal part of the NTS.
Prior administration of the α‐adrenoceptor blocking agent, phentolamine, reversed the fall in blood pressure and heart rate induced by α‐methylnoradrenaline into an increase.
Systemic administration of atropine combined with vagotomy potentiated the inhibitory effects of α‐methylnoradrenaline on the cardiovascular system.
FURTHER EVIDENCE THAT PROSTAGLANDINS INHIBIT THE RELEASE OF NORADRENALINE FROM ADRENERGIC NERVE TERMINALS BY RESTRICTION OF AVAILABILITY OF CALCIUM
Authors: HEDQVIST P. 
Published: July 2012

Guinea‐pig vasa deferentia were continuously superfused after labelling the transmitter stores with [3H]‐(—)‐noradrenaline. Release of [3H]‐(—)‐noradrenaline was induced by transmural nerve stimulation.
Prostaglandin E2 (14 nm) drastically reduced the release of [3H]‐(—)‐noradrenaline, while tetraethylammonium (2 mm), rubidium (6 mm), phenoxybenzamine (3 μm) each in the presence or absence of Uptake 1 or 2 blockade, and prolonged pulse duration (from 0.5 to 2.0 ms) all significantly increased the release of [3H]‐(—)‐noradrenaline per nerve impulse.
The inhibitory effect of prostaglandin E2 on evoked release of [3H]‐(—)‐noradrenaline was significantly reduced by tetraethylammonium, rubidium and prolonged pulse duration, whilst it was actually enhanced by phenoxybenzamine. This indicates that increased release of noradrenaline per nerve impulse does not per se counteract the inhibitory effect of prostaglandin E2.
It is concluded that tetraethylammonium, rubidium and prolonged pulse duration counteracted the inhibitory effect of prostaglandin E2 on [3H]‐(—)‐noradrenaline release by promoting calcium influx during the nerve action potential. The results are consistent with, and add more weight to the view that prostaglandins inhibit the release of noradrenaline by restriction of calcium availability.
THE IONIZATION OF PHENOLIC AMINES, INCLUDING APOMORPHINE, DOPAMINE AND CATECHOLAMINES AND AN ASSESSMENT OF ZWITTERION CONSTANTS
Authors: ARMSTRONG J. , BARLOW R.B. 
Published: July 2012

The dissociation constants of many phenolic amines, including benzylamines, phenethylamines, phenylethanolamines, phenylpropylamines, catecholamines, and apomorphine have been measured by potentiometric titration at 25°C. Measurements have also been made with many of their methoxy derivatives and with series of phenolic quaternary ammonium salts. Some compounds were also studied at 37°C.
Usually at least five titrations were made with each compound and Debye—Hückel theory was applied to convert concentrations to activities but the estimates of pKa were not constant and found to increase with increasing concentration. The range studied was usually 5–15 mm and a least‐squares line‐fit, based on the empirical assumption that pKa varies with (concentration)1/2, has been used to calculate values for 10 mm solutions and to extrapolate to infinite dilution and to 100 mm. The dependence of pKa on concentration was much less at 37°C than at 25°C.
At 37°C the pKa values of many biologically interesting compounds in the group, dopamine, noradrenaline, adrenaline and isoprenaline, coryneine (the trimethylammonium derivative of dopamine) and apomorphine are within 1 log unit of physiological pH, indicating the presence of a significant proportion of either the zwitterion or of the uncharged phenolic amine.
Zwitterion constants have been estimated from the pKa values of the phenolic amines and those of their methoxy and quaternary trimethylammonium analogues. Zwitterion formation does not appear to be associated with activity at α‐adrenoceptors and probably not with activity at β‐receptors. The active species seems likely to contain the unionised phenolic group but at dopamine receptors this may be in the uncharged phenolic amine rather than in the phenolic ammonium salt.
THE EFFECTS OF MORPHINE ON THE RELEASE OF NORADRENALINE FROM THE MOUSE VAS DEFERENS
Authors: HENDERSON G. , HUGHES J. 
Published: July 2012

Electrical field stimulation of the mouse vas deferens (TO and C57/BL strains) caused the release of noradrenaline into the bathing medium.
Phenoxybenzamine (30 μm) or phentolamine (36 μm) plus cocaine (13 μm) caused a considerable increase in the noradrenaline output.
In the vasa deferentia from TO mice the output per pulse of noradrenaline was constant at frequencies of stimulation from 0.5 to 15 Hz whereas in the vasa deferentia from C57/BL mice the output per pulse of noradrenaline increased two‐fold from 1.5 to 15 Hz.
Morphine (2 μm) inhibited the contractions of the vasa deferentia from TO mice. This effect was greater at low (0.1‐1 Hz) than at high (10 Hz) frequencies of stimulation. Morphine (2 μm) did not inhibit the response of the tissue to exogenous noradrenaline.
Morphine (1 μm) reduced the noradrenaline output from the vasa deferentia of TO mice stimulated at 1.5 Hz but did not reduce the noradrenaline output at 15 Hz. At 1.5 Hz the reduction of noradrenaline output was reversed by naloxone (0.05 μm).
Morphine (5 μm) did not inhibit the uptake of [3H]‐noradrenaline into the vasa deferentia from TO mice.
Only in high concentrations (ID50 30.88 μm) did morphine inhibit the contractions of the vasa deferentia from C57/BL mice.
Normorphine (100 μm) did not reduce the noradrenaline output from vasa deferentia of C57/BL mice.
THE POSSIBLE INVOLVEMENT OF Na+ IONS IN CORTICOSTERONE‐INDUCED HYPERCONTRACTILITY IN THE RAT ANOCOCCYGEUS MUSCLE
Authors: GIBSON A. , POLLOCK D. 
Published: July 2012

The possibility that corticosterone‐induced hypercontractility in the rat anococcygeus muscle might be due to an intramuscular redistribution of Na+ was investigated.
The contractility of the isolated muscle to noradrenaline (NA) was directly dependent on the Na+ concentration of the Krebs solution.
There was a linear relationship between the maximum contractile response of the muscle to NA and the Na+ concentration of the Krebs solution.
Muscle contractility was also increased by the presence of ouabain (10−4m) in the bathing medium.
Muscles from rats treated with corticosterone exhibited increases in both total and ouabain‐sensitive ATPase activity.
The relationship between corticosterone, Na+ distribution, and muscle contractility is discussed.
THE VASODILATOR ACTIONS OF ISOPRENALINE, HISTAMINE, PROSTAGLANDIN E2, GLUCAGON AND SECRETIN ON THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG
Authors: RICHARDSON P.D.I. , WITHRINGTON P.G. 
Published: July 2012

The sympathetically‐innervated arterial vascular bed of the dog's liver was perfused from a femoral artery. Arterial blood flow and perfusion pressure were measured continuously, and the hepatic arterial vascular resistance calculated. The preparation provided a means of assessing hepatic arterial vasodilatation quantitatively.
Isoprenaline, histamine, prostaglandin E2, glucagon and secretin were injected intra‐arterially and all evoked dose‐dependent vasodilatation of the hepatic arterial vascular bed.
The maximum reduction in the calculated hepatic arterial vascular resistance of 37–38% was the same for each of the five substances.
Comparisons on a weight basis revealed that prostaglandin E2 was the most potent, followed in potency order by secretin, isoprenaline, histamine and glucagon.
Comparisons on a molar basis showed that secretin and prostaglandin E2 were intrinsically considerably more potent than isoprenaline, histamine or glucagon.
The onset of the vasodilatator responses to secretin, isoprenaline, histamine and prostaglandin E2 was rapid, and the duration of their actions was brief.
The onset of the vasodilator effects of glucagon was slow and its duration of action very prolonged.
The implications of these observations with respect to the physiological control of the hepatic arterial vascular bed of the dog are discussed.
A RAPID METHOD FOR THE ESTIMATION OF PROSTAGLANDIN 15‐HYDROXYDEHYDROGENASE ACTIVITY AND ITS APPLICATION TO PHARMACOLOGY
Authors: BLACKWELL G.J. , FLOWER R.J. 
Published: July 2012

A novel double‐isotope assay for prostaglandin 15‐hydroxydehydrogenase (PGDH) is described.
The assay is simple, rapid, precise, completely specific for PGDH, and free from artefacts. The results obtained correlate well with a conventional assay.
The method is versatile, being applicable to estimations of enzyme activity in cell‐free systems as well as perfused organs, and is well suited to the assay of PGDH inhibitors.
POSSIBLE INFLUENCE OF INTRARENAL GENERATION OF KININS ON PROSTAGLANDIN RELEASE FROM THE RABBIT PERFUSED KIDNEY
Authors: COLINA‐CHOURIO J. , McGIFF J.C. , MILLER M.P. , NASJLETTI A. 
Published: July 2012

The effects of bradykinin and kininogen on renal prostaglandin release were studied in rabbit isolated kidneys perfused with oxygenated Krebs solution.
The concentration of prostaglandin‐like material in kidney effluent was determined by bioassay after extraction of the samples with organic solvents. In 7 experiments the samples were assayed after separation of prostaglandins E and F by thin layer chromatography.
Addition of bradykinin to the perfusing fluid increased the venous and urinary effluxes of prostaglandin E‐like substance by sixfold and fivefold, respectively, but efflux of prostaglandin F‐like material was unaffected.
Addition of kininogen to the perfusing fluid augmented the venous and urinary release of prostaglandin E‐like substances by fifteenfold and ninefold respectively and caused a twofold increase in the efflux of prostaglandin F‐like material into the venous effluent.
Aprotinin, a kallikrein inhibitor, reduced the prostaglandin releasing action of kininogen but not of bradykinin. In contrast, inhibition of prostaglandin synthesis by indomethacin suppressed the release of prostaglandin evoked by either bradykinin or kininogen.
This study suggests that augmented release of prostaglandins in response to kininogen is a consequence of renal generation of kinins. Thus, changes in the intrarenal activity of the kallikreinkinin system may modulate renal prostaglandin release.
THE β‐ADRENOCEPTOR OF THE HUMAN LYMPHOCYTE AND HUMAN LUNG PARENCHYMA
Authors: CONOLLY M.E. , GREENACRE J.K. 
Published: July 2012

The response of the β‐adrenoceptors of human lymphocytes to selective agonists and antagonists has been studied quantitatively by measuring changes in cyclic adenosine‐3′,5′‐monophosphate (cyclic AMP) levels.
The receptor was activated by isoprenaline and by salbutamol, and blocked by propranolol but not by practolol. A similar pattern of response was obtained with fragments of human lung tissue.
The mean value for pA2 for propranolol was 8.34 and for practolol was 3.95.
These findings indicate that the lymphocyte β‐adrenoceptor is a β2‐receptor and support the validity of using lymphocytes to study β‐adrenoceptor function in bronchial asthma. It may also be of use in the evaluation of selective β2‐blocking drugs in man.
THEOPHYLLINE AND PHENYLEPHRINE EFFECTS ON CARDIAC RELAXATION
Authors: BENFEY B.G. 
Published: July 2012

In the driven isolated left atrium of the rabbit theophylline shortened relaxation time in a similar manner to isoprenaline and histamine.
Phenylephrine lengthened relaxation time in a similar manner to calcium.
Theophylline caused phenylephrine to shorten relaxation time, which was inhibited by a β‐adrenoceptor blocking drug, but theophylline did not potentiate the effect of phenylephrine on peak tension.
Theophylline separated drug effects on cardiac relaxation and contraction: in the presence of theophylline at a low calcium concentration, phenylephrine shortened relaxation time by β‐adrenoceptor stimulation and increased peak tension by α‐adrenoceptor stimulation. At a high calcium concentration, theophylline potentiated the effect of isoprenaline, histamine and phenylephrine on relaxation time but inhibited the effect on peak tension.
PULMONARY METABOLISM OF BRADYKININ ANALOGUES AND THE CONTRIBUTION OF ANGIOTENSIN CONVERTING ENZYME TO BRADYKININ INACTIVATION IN ISOLATED LUNGS
Authors: BAKHLE Y.S. 
Published: July 2012

The activity and pulmonary metabolism of two peptides, 7‐homo Pro‐bradykinin and 8‐homo Phe‐bradykinin were studied in isolated systems.
Both analogues were about 50–70 times less active than bradykinin on the guinea‐pig ileum and 70–160 times less active on isolated strips of cat terminal ileum.
The action of both analogues on guinea‐pig ileum was potentiated (2.5‐3.0 fold) by a bradykinin potentiating peptide (BPP9a) but less so than the action of bradykinin (4–5 fold).
Like bradykinin, the 8‐homo Phe analogue was extensively inactivated (>90%) in a single passage through the pulmonary circulation of guinea‐pig or rat isolated lungs and this inactivation was prevented by pre‐treatment of the lungs with BPP9a.
The 7‐homo Pro analogue was inactivated to a lesser degree in guinea‐pig lungs (58%) and in rat lungs (89%) and its inactivation was not affected by BPP9a.
It is concluded that the 8‐homo Phe analogue is a substrate for the dipeptidylcarboxypeptidase (angiotensin I converting enzyme) of lung, whereas the 7‐homo Pro analogue is not a substrate.
There is about four times as much dipeptidylcarboxypeptidase activity in guinea‐pig isolated lungs as there is in rat isolated lungs.
THYROID HORMONE‐DEPENDENT INTERCONVERSION OF MYOCARDIAL α‐ AND β‐ADRENOCEPTORS IN THE RAT
Authors: KUNOS G. 
Published: July 2012

The effects of thyroid state on the properties of adrenoceptors mediating inotropic and chronotropic responses of the rat heart were assessed on the basis of the relative potencies of α‐ and β‐adrenoceptor agonists, the effects of α‐ and β‐adrenoceptor antagonists and the tissue uptake of [3H]‐phenoxybenzamine ([3H]‐PB).
In isolated, electrically driven left atria the ratio of the inotropic potencies of isoprenaline and phenylephrine and the inhibitory potency of propranolol (40nM‐4 μm) were significantly reduced after thyroidectomy and were moderately increased after thyroxine treatment of control rats.
Block of inotropic responses to noradrenaline and to phenylephrine by PB (7.3nM‐7.3 μm) and the tissue uptake of [3H]‐PB were significantly greater in preparations from thyroidectomized than in those from control or from thyroxine treated rats. α‐Adrenoceptor inhibition by phentolamine (0.26‐2.6 μm) also increased after thyroidectomy, and phentolamine effectively protected α‐adrenoceptors from block by and binding of [3H]‐PB.
The β1‐receptor antagonist H 93/26 (0.1 μm) significantly potentiated α‐adrenoceptor blockade by PB in hypothyroid but not in control preparations.
In spontaneously beating right atria the chronotropic potency of agonists and the effects of antagonists were altered in the same way as were inotropic responses and the slope of the agonist concentration‐response curves were significantly reduced after thyroidectomy. Effects of agonists and antagonists were not significantly influenced by thyroxine treatment.
Changes in the effects and tissue uptake of sympathomimetic drugs observed after thyroidectomy were reversed to or beyond control levels by thyroid hormone treatment of thyroidectomized animals.
The results presented are interpreted as indicating a thyroid hormone‐dependent interconversion of myocardial α‐ and β‐adrenoceptors. It is suggested that this interconversion is similar to that observed earlier in frog hearts at different temperatures, and that both effects may reflect an allosteric transition between two forms of a single basic structure.
ANAPHYLACTIC CONTRACTION OF PULMONARY BLOOD VESSELS OF CHICKEN
Authors: CHAND N. , EYRE P. 
Published: July 2012

Isolated pulmonary arterial and vein strips from sensitized or non‐sensitized chickens exhibited dose‐dependent contractions to adrenaline>, noradrenaline>, 5‐hydroxytryptamine>, histamine>, dopamine. Individual variability in the responsiveness of the vessels to agonists was marked. In general veins were 2 to 25 times more sensitive to agonists than arterial strips.
Isoprenaline (a relatively specific β‐adrenoceptor agonist) induced relaxations of the submaximally contracted pulmonary vein and arteries at low doses and contractions at high concentrations.
Contractile responses to acetylcholine or carbachol were not regularly recorded; only 50% of the vessels reacted to cholinoceptor agonists over a wide threshold dose range.
Chicken pulmonary vessels were found relatively insensitive to bradykinin.
Effects of prostaglandins were variable. Prostaglandin induced dose‐related contractions of the vein and arterial strips; prostaglandins E1 and E2 at low doses relaxed partially contracted pulmonary artery irrespective of the spasmogen used and further increase in doses induced either no effect or contractions. Prostaglandin E1 induced marked and rapid contractions of the vein. Prostaglandin E2 induced relaxations of the prostaglandin F2α‐contracted vein only, but produced no effect or slight contractions of the veins partially contracted to other spasmogens.
Pulmonary arterial and vein strips obtained from chickens sensitized to horse plasma exhibited Schultz‐Dale contractions of variable magnitude and duration to specific antigenic challenge only. In many vessels, antigen‐induced contractions were associated with marked increase in spontaneous activity.
The importance of the Schultz‐Dale reaction in avian pulmonary vessels is discussed in relation to the right heart dilatation associated with anaphylaxis in the chicken.
THE EFFECTS OF METIAMIDE ON CELL‐MEDIATED IMMUNE REACTIONS IN THE GUINEA‐PIG
Authors: DALE M. MAUREEN 
Published: July 2012

1 The effects of the H2‐receptor antagonist, metiamide, on two types of cell‐mediated immune response in vivo was investigated in the guinea‐pig, in a test of the hypothesis that H2‐receptor antagonists would result in ‘runaway’ unregulated hypersensitivity reactions.2 Metiamide in doses of 5 mg‐125 mg/kg given by 6‐hourly injection during sensitization and challenge did not modify the delayed hypersensitivity reaction to tuberculin.3 Metiamide in doses of 25‐125 mg/kg given by injection, 6‐hourly throughout sensitization to dinitrofluorobenzene (DNFB) and subsequent challenge six days later, did not modify the contact sensitivity reaction to DNFB.4 It is concluded that metiamide, given during these cell‐mediated immune reactions in the guinea‐pig, does not enhance cell‐mediated hypersensitivity responses.
EFFECTS OF N‐METHYLAMINO ACIDS AND CONVULSANTS ON SPONTANEOUS ACTION POTENTIALS IN GUINEA‐PIG CEREBELLAR SLICES
Authors: OKAMOTO K. , QUASTEL J.H. 
Published: July 2012

N‐methyl‐γ‐aminobutyrate (N‐methylGABA), N‐methylglycine, N‐methyltaurine and N‐methylβ‐alanine diminished the frequency of spontaneous spike discharges in guinea‐pig cerebellar slices. Usually a weak excitatory effect preceded the inhibition.
The inhibitory effects of N‐methylGABA and N‐methylβ‐alanine were competitively antagonized by both picrotoxin and strychnine.
The inhibitory action of N‐methyltaurine was competitively suppressed by strychnine and by low concentrations of picrotoxin.
The inhibitory action of N‐methylglycine was suppressed by strychnine but not by picrotoxin. The suppression was competitive at low concentrations of strychnine.
N‐methyldl‐glutamate brought about a strong inhibition followed by a strong excitation of the neurones. The inhibitory effects were competitively suppressed by both picrotoxin and strychnine. Neither convulsant affected the excitation.
Whereas l‐ or D‐glutamate caused only excitation in the majority of cells examined, a small proportion of the cells exhibited inhibition preceding the excitation by l‐ or D‐glutamate. Such inhibitory effects were suppressed by picrotoxin but not by strychnine.
Kinetic analyses of the dose‐response curves for the N‐methylamino acid in the presence or absence of the convulsant indicated that the number of molecules of the amino acid combining with the receptor site to produce a response was 3 for N‐methylGABA, 2 for N‐methylglycine, 3 for N‐methyltaurine, 3 for N‐methylβ‐alanine. The corresponding value was 1 for N‐methyldl‐glutamate (inhibition). The number of molecules of convulsant combining with the receptor site was calculated to be 2 for picrotoxin with N‐methylGABA, N‐methylβ‐alanine and N‐methyldl‐glutamate and 1 for strychnine with all N‐methylamino acids examined.
THE FATE OF BIOGENIC MONOAMINES IN PERFUSED RABBIT LUNG
Authors: GILLIS C.N. , ROTH J.A. 
Published: July 2012

Inactivation of β‐phenylethylamine and several of its derivatives was studied in a preparation of rabbit lung perfused with Krebs physiological medium at 37°C. Inactivation or removal of these compounds was calculated as the difference between the concentration of each amine in the perfusion medium and the effluent, collected separately from each lung. The extent of amine metabolic degradation was also measured, by column chromatography, in lung effluent.
With this technique the magnitude of amine removal as a function of concentration was determined and an apparent Km and Vmax of removal were calculated for each amine.
Percentage removal was highest with phenylethylamine (95%), and decreased, apparently in relation to increasing phenyl‐ and side chain‐hydroxylation (and therefore likely increased hydrophilicity), with 5‐hydroxytryptamine (64%), tyramine (53%), octopamine (35%), dopamine (32%) and noradrenaline (23%).
Inactivation of each amine could be accounted for by metabolic degradation to deaminated products, which appeared in lung effluent within 90 s of beginning amine perfusion.
When intrapulmonary metabolism of phenylethylamine was inhibited by simultaneous perfusion with semicarbazide (10 mM) and pargyline (10 μM), the removal rate was unaltered, establishing that uptake of the amine from the vascular space is not dependent on metabolism at least for 4 min infusions.