bluuebunny/crossref_metadata_2025_split huggingface dataset:
STRUCTURE‐ACTIVITY RELATIONSHIP OF IMIDAZOLIDINE DERIVATIVES RELATED TO CLONIDINE AT HISTAMINE H2‐RECEPTORS IN GUINEA‐PIG ISOLATED ATRIA
Authors: McCULLOCH M.W. , MEDGETT I.C. , RAND M.J. , STORY D.F. 
Published: July 2012

Cumulative concentration‐response relationships for the chronotropic effects of histamine, oxymetazoline, clonidine and thirteen clonidine‐like imidazolidine derivatives were examined in isolated spontaneously beating guinea‐pig atria.
The following compounds induced positive chronotropic effects: histamine, clonidine (2,6‐dichlorophenyliminoimidazolidine) and the 2,6‐dibromo, 2,6‐dimethyl, 2,6‐diethyl, 2,6‐dihydroxy, 2,4,6‐trimethyl, 3,4‐dihydroxy and 2‐methyl‐5‐fluoro analogues of clonidine. These compounds appeared to act as partial agonists on histamine H2‐receptors, with potencies ranging from one tenth to one hundredth and intrinsic activities from approximately 20% to 75% of those of histamine.
The following compounds did not induce positive chronotropic effects but rather decreased the atrial rate, usually at high concentrations: oxymetazoline and the 2,3‐dichloro, 4‐dichloro, 5‐dichloro, 2‐chloro‐4‐methyl, 2‐methyl‐5‐chloro, 2,4,6‐trichloro analogues of clonidine.
The effects of histamine were antagonized by cimetidine, the pA2 value being 6.68 (s.e. mean = 0.16, n = 3), and also in a concentration‐dependent manner by clonidine. Cimetidine antagonized the response to clonidine in a concentration‐dependent manner; however, high concentrations of cimetidine depressed the maximal response to clonidine and the slope of the concentration‐response curve was no longer parallel to the control curve.
The effects of the other compounds which induced positive chronotropic effects were also antagonized by cimetidine (1 μmol/l); however, the effect of the 3,4‐dihydroxy derivative was unaffected by cimetidine (1 μmol/l) but was abolished by propranolol (0.3 μmol/l).
In general, phenyliminoimidazolidine derivatives with 2,6‐substitution on the phenyl ring are active on histamine H2‐receptors, whereas derivatives with 2,3‐, 2,4‐ or 2,5‐substitutions are weakly active or inactive. Thus the restriction imposed on the free rotation of the phenyl ring about the carbon‐imino nitrogen bond by the introduction of two ortho substituents appears to result in increased agonist activity on the histamine H2‐receptor. The introduction of substituents in the 3, 4 or 5 positions in the phenyl ring may lead to compounds sterically hindered from combining with the histamine H2‐receptor.
There is no apparent relationship between the activities of clonidine‐like imidazolidine derivatives as agonists on histamine H2‐receptors and their hypotensive activities (as reported in the literature).
ACTIONS OF NITROGLYCERINE ON THE MEMBRANE AND MECHANICAL PROPERTIES OF SMOOTH MUSCLES OF THE CORONARY ARTERY OF THE PIG
Authors: ITO YUSHI , KITAMURA KENJI , KURIYAMA HIROSI 
Published: July 2012

Effects of nitroglycerine (NG) on the membrane and contractile properties of the smooth muscle cell of the isolated coronary artery of the pig were observed.
NG, up to a concentration of 10−5 m, modified neither the membrane potential nor the membrane resistance. Increased concentrations of NG (> 2.8 × 10−5 m) hyperpolarized the membrane, reduced the membrane resistance and enhanced the rectifying property of the membrane measured by depolarization pulses. These phenomena observed with a high concentration of NG are the result of an increase in the K‐conductance of the membrane.
NG (2.8 × 10−5 m) did not modify the membrane potential displaced by various concentrations of excess [K]o. In low [K]o, NG (2.8 × 10−5 m) hyperpolarized the membrane to a greater extent than that observed in Krebs solution. The effects of NG (10−6 to 2.8 × 10−5 m) on the membrane potential were not modified by simultaneous application of 2 × 10−6 m acetylcholine (ACh).
NG (2.8 × 10−6 m) consistently raised the mechanical threshold required for tension development and suppressed the amplitude of the contraction evoked by excess [K]o, ACh or electrical depolarization of the membrane. The dose‐response curve shifted to the right in the presence of NG noncompetitively in all the conditions employed to develop the tension.
When the tissue was immersed in Ca‐free (EGTA) solution, ACh (5 × 10−6 m) evoked a contraction even after the tissue had lost the ability to contract to repetitive applications of 118 mm [K]o in Ca‐free (EGTA) solution. However, the tissue finally failed to contract to repetitively applied ACh. At this stage, 2.5 mm [Ca]o evoked a small contraction, after which the response was briefly restored to 5 × 10−6 m ACh. This transient response to ACh was reduced by NG (5.6 × 10−6 m) when NG was added either simultaneously with ACh or with the previous Ca application. However, the inhibition was greater in the former than the latter case.
Cysteine (1 to 2 mm), without modifying the membrane potential or membrane resistance, partly restored the contraction evoked by excess [K]o or ACh which had been reduced by NG.
The mechanism of action of NG on the smooth muscle cell of the coronary artery of the pig is postulated to be due to a nonselective suppression of the Ca‐mobilization from the store site with no noticeable change in the membrane properties.
PRESSURE REVERSAL OF THE EFFECT OF URETHANE ON THE EVOKED SOMATOSENSORY CORTICAL RESPONSE IN THE RAT
Authors: ANGEL A. , GRATTON DENISE A. , HALSEY M.J. , WARDLEY‐SMITH BRIDGET 
Published: July 2012

The cerebral response evoked by stimulation of the forepaw in the rat shows an increase in latency and decrease in the amplitude of its initial components as anaesthetic dose (urethane) is increased.
These changes are reversed if the ambient pressure is increased with helium and the electrocorticogram shows an increase in basic frequency.
The dose of urethane needed to prevent reflex response to tail stimulation is increased as pressure increases.
The implications of these behavioural and somatosensory responsiveness changes as pressure is increased are discussed.
ACTIONS OF 4‐AMINOPYRIDINE ON VASCULAR SMOOTH MUSCLE TISSUES OF THE GUINEA‐PIG
Authors: HARA YUSUKE , KITAMURA KENJI , KURIYAMA HIROSI 
Published: July 2012

Effects of 4‐aminopyridine (4‐AP) and procaine on the membrane and contractile properties of smooth muscle cells of the guinea‐pig pulmonary artery and portal vein were observed.
The membrane potential and length constant of smooth muscle cells of the guinea‐pig pulmonary artery were −53.2 mV and 1.2 mm, respectively, and those of the portal vein were −52.6 mV and 0.71 mm, respectively. The membrane was electrically quiescent in the pulmonary artery and it was electrically active in the portal vein.
Both 4‐AP and procaine depolarized the membrane, increased the membrane resistance and suppressed the rectifying properties in both tissues. Both agents evoked a graded response from the muscle membranes of the pulmonary artery by outward current pulse. Procaine had a greater effect than 4‐AP on the above membrane properties.
4‐AP (10−5 m) produced contraction without depolarization of the membrane. The contraction evoked by 10−5 m 4‐AP was completely suppressed but that evoked by 5 × 10−4 m 4‐AP was only partly suppressed by phentolamine (10−7 m). However, the contraction evoked by procaine was not suppressed by phentolamine.
4‐AP enhanced but procaine suppressed the amplitude of 118 mm [K]0‐induced contraction.
The results suggest that 4‐AP and procaine suppress K‐conductance of the muscle membrane, and 4‐AP but not procaine increases noradrenaline release from the nerve terminal. Presumably intracellular free Ca concentrations are also modified by these agents. The effects of 4‐AP and procaine on the vascular muscle were compared with those on other excitable tissues.
INHIBITION OF THE ACETYLCHOLINE RECEPTOR BY HISTRIONICOTOXIN
Authors: ANWYL ROGER , NARAHASHI TOSHIO 
Published: July 2012

The action of C5‐decahydrohistrionicotoxin (C5‐HTX) has been investigated on the extrajunctional acetylcholine (ACh) receptors of denervated rat muscle.
C5‐HTX causes both a rapid and slow reduction in amplitude of iontophoretic ACh potentials evoked at all frequencies from the extrajunctional receptors.
C5‐HTX also causes a time‐dependent inhibition of the iontophoretic potentials evoked at frequencies greater than 0.02 Hz. This inhibition was observed either alone or superimposed upon desensitization, and may be caused by a similar mechanism to desensitization.
EFFECTS OF MORPHINE ON CANINE INTESTINAL ABSORPTION AND BLOOD FLOW
Authors: MAILMAN DAVID 
Published: July 2012

Intestinal absorption and blood flow were determined in anaesthetized fed or fasted dogs following rapid intravenous injections of morphine (0.01, 0.1, 1 mg/kg).
3H2O and 22Na were used to determine the unidirectional fluxes of Na+ and H2O from saline perfused through the ileal lumen and the clearances of 3H2O were used to determine total and absorptive site blood flow.
Net Na+ and H2O absorption were increased at each dose of morphine in fed but not in fasted dogs, due primarily to increased absorptive fluxes.
Arterial pressure was decreased by morphine but mesenteric vein pressure was little affected. Absorptive site blood flow was increased by morphine due to decreased blood flow resistance but total blood flow resistance was little affected by morphine.
The absorptive fluxes of Na+ and H2O were correlated with absorptive site blood flow in both fed and fasted animals. The secretory fluxes of Na+ and H2O were correlated with estimated capillary pressure in fasted dogs but morphine decreased the secretory fluxes at a given capillary pressure in dogs which had been fed.
Naloxone (0.12 mg, i.v.) reversed the effects of morphine. The effects of morphine on the gut were reversed more slowly than on systemic blood pressure.
It was concluded that morphine can increase net absorption in fed dogs by a selective increase in intestinal absorptive site blood flow and thus increase absorptive fluxes by a washout effect but that there is also an epithelial effect, sensitized by feeding, which reduces the secretory fluxes of Na+ and H2O.
In vitro ACTIVITY OF RO363, A β1‐ADRENOCEPTOR SELECTIVE AGONIST
Authors: IAKOVIDIS D. , MALTA E. , McPHERSON G.A. , RAPER C. 
Published: July 2012

The β‐adrenoceptor stimulant effects of RO363 and (−)‐isoprenaline have been compared in a variety of isolated tissue preparations.
RO363 is approximately half as potent as (−)‐isoprenaline in tissues where actions are due to β1‐receptor activation (guinea‐pig atrial and ileal preparations and ventricular strips from the rabbit, rat and guinea‐pig).
In uterine and lung strip preparations from the guinea‐pig, where responses are due to β2‐receptor stimulation, RO363 is 100 to 350 times less active than (−)‐isoprenaline and has a low intrinsic activity.
In spontaneously contracted tracheal preparations from the guinea‐pig, RO363 is a full agonist and is approximately half as potent as (−)‐isoprenaline. These effects of RO363 are due to the activation of a population of β1‐receptors in the tissue since RO363 and (−)‐isoprenaline have the same relative potencies in trachea, cardiac and ileal preparations. In addition the KB values for practolol are similar in all these preparations when RO363 is used as the agonist.
The results show that RO363 is a potent and highly selective β1‐receptor agonist.
RELEASE OF OPIOID PEPTIDES IN ANAESTHETIZED CATS?
Authors: DASHWOOD M.R. , FELDBERG W. 
Published: July 2012

The effect on arterial blood pressure of intravenous injections of naloxone (200 μg) was examined in cats anaesthetized with chloralose. Usually these injections have no effect on blood pressure unless morphine or opioid peptides have been injected, when they produce a pressor response with tachycardia.
It was found that these injections produced a pressor response with tachycardia after a combination of two or more of the following surgical procedures: (1) tying sinus nerves, (2) removing stellate ganglia, (3) cutting vagi, (4) evisceration.
The pressor responses obtained in these conditions are taken as evidence that such procedures induce the release of endogenous opioid peptides.
The pressor responses to naloxone were greatest when all four surgical procedures had been performed and were then due to adrenaline secretion, evoked centrally by a sympathetic discharge to the adrenals.
If either the stellate ganglia or the viscera were left intact, but the remaining three surgical procedures performed, then the pressor responses to naloxone were due to a sympathetic discharge to adrenals and to blood vessels.
In cats that had received a subcutaneous injection of morphine (2 mg/kg) the adrenals played a minor role in the pressor responses to naloxone, unless the four surgical procedures had been performed. Then the adrenals became entirely responsible for them.
The opioid peptides released after the surgical procedures may be enkephalins or the C‐fragment of lipotropin (β‐endorphin). The stimulus for their release may be interruption of afferent sensory pathways from viscera or the ‘stress’ associated with the surgical procedures.
A STUDY OF SOME PROPRANOLOL ANALOGUES FOR SELECTIVE β‐ADRENOCEPTOR ANTAGONISM USING pA2 VALUES ON ISOLATED TRACHEA AND ATRIA FROM GUINEA‐PIG
Authors: O'DONNELL STELLA R. , WALDUCK KARIN , WANSTALL JANET C. 
Published: July 2012

pA2 values for β‐adrenoceptor antagonists were obtained on isolated preparations of guinea‐pig trachea (intrinsic tone) and atria (rate), with isoprenaline, noradrenaline (β1‐selective) and fenoterol (β2‐selective) as agonists. Uptake mechanisms and α‐adrenoceptors were inhibited. The antagonists studied were (±)‐threo‐α‐methylpropranolol, (±)‐1‐(4‐benzimidazoloxy)‐3‐isopropylamino‐2‐propanol (4‐BIP) and (±)‐1‐(5‐benzimidazoloxy)‐3‐isopropylamino‐2‐propanol (5‐BIP).
4‐BIP was a potent β‐adrenoceptor antagonist but it was not selective for trachea (pA2 on trachea 7.88 and on atria 7.73, fenoterol as agonist). 5‐BIP was less than one tenth as active as 4‐BIP and was therefore not studied in detail.
α‐Methylpropranolol was potent and it was also selective for trachea (pA2 on trachea 8.24 and on atria 7.56, fenoterol as agonist). This selectivity was not seen with isoprenaline as agonist. In tracheal preparations contracted by carbachol the slope of the Schild plot for α‐methylpropranolol was less than 1.0 (isoprenaline as agonist).
α‐Methylpropranolol, although not highly selective for β2‐adrenoceptors, is considerably more potent than the alternative β2‐selective antagonists available at present. Therefore, it may be useful in studies designed to classify β‐adrenoceptor subtypes in tissues.
β2‐ADRENOCEPTORS MEDIATE THE STIMULATING EFFECT OF ADRENALINE ON ACTIVE ELECTROGENIC NA‐K‐TRANSPORT IN RAT SOLEUS MUSCLE
Authors: CLAUSEN T. , FLATMAN J.A. 
Published: July 2012

The relative role of β1‐ and β2‐adrenoceptors in mediating the stimulating effect of adrenaline on active electrogenic Na‐K‐transport has been assessed in experiments on rat soleus muscles in vitro and in vivo.
In the rat isolated soleus muscle, adrenaline (10−6 m) increases the resting membrane potential (EM) by 5.8 mV and stimulates 22Na‐efflux and ouabain‐suppressible 42K‐uptake by 91 and 94%, respectively.
All of these effects are completely blocked by propranolol (10−5 m), whereas the β1,‐selective adrenoceptor antagonist, metoprolol, was found to be at least 50 times less potent.
The β2‐adrenoceptor agonist, salbutamol, was at least 100 times as potent as H133/22 (a β1‐selective agonist) in stimulating 22Na‐efflux and 42K‐influx.
In experiments performed under pentobarbitone anaesthesia, the intravenous injection of adrenaline (5 μg) or salbutamol (0.5 to 50 μg) led to a rapid and marked increase in the EM of the exposed soleus muscle. This hyperpolarizing effect could not be accounted for by the concomitant, relatively modest change in extracellular K.
CORRELATION BETWEEN CATECHOLAMINE SECRETION FROM BOVINE ISOLATED CHROMAFFIN CELLS AND [3H]‐OUABAIN BINDING TO PLASMA MEMBRANES
Authors: AUNIS DOMINIQUE , GARCÍA ANTONIO G. 
Published: July 2012

Secretion of catecholamines (CA) evoked by ouabain, chlormadinone acetate (CMA), phenoxybenzamine (Pbz) and vanadate, four agents known to inhibit Na+, K+‐dependent Mg2+‐activated adenosine triphosphatase (ATPase) activity has been studied in suspensions of bovine isolated adrenal medullary cells.
Acetylcholine (ACh) evoked a 5 fold increase of the basal CA secretion from isolated cells suspended in oxygenated Krebs‐bicarbonate solution kept at 27°C. Secretion was antagonized by Ca2+‐deprivation or hexamethonium, indicating good functional viability of the cells.
Ouabain (10−7to 10−4m) evoked a progressive, dose‐dependent release of CA from cell suspensions. Study of the time course of the secretory response for 2h allowed the separation of two components in the secretory response at all doses studied: a slow initial component (0.011 pg/min CA) and a second faster component (0.032 pg/min CA).
CMA evoked a clear‐cut CA secretory response. The ED50for CMA was 10−4m, as compared to 3 × 10−6m for ouabain. Pbz and vanadate did not induce CA release.
[3H]‐ouabain was taken up and bound to intact isolated cells by a non‐saturable binding process. However, in semi‐purified plasma membranes from bovine adrenal medulla a saturable specific [3H]‐ouabain binding process was observed with a KD of 8.1 nm. Binding to the membranes was ATP‐dependent and antagonized by K+.
[3H]‐ouabain specific binding to membranes was antagonized by ouabain and CMA, but not by Pbz or vanadate; the ID50 for ouabain and CMA were 10−6and 10−5m respectively.
Ouabain partially inhibited, in a dose‐dependent manner, Na+, K+‐Mg2+ATPase activity of the semi‐purified plasma membranes.
The results demonstrate a good correlation between the ability of different drugs, known to inhibit ATPase activity, to displace [3H]‐ouabain binding to adreno—medullary plasma membranes and their capacity to evoke a CA secretory response from isolated chromaffin cells. The data also suggest that the CA secretory effects of ouabain may not be due simply to inhibition of the Na+pump and the subsequent ionic redistribution across the plasma membrane; a second mechanism may also be involved.
THE ANTICOAGULANT ACTIVITY OF DERMATAN SULPHATES: EVIDENCE AGAINST THE INVOLVEMENT OF ANTITHROMBIN III
Authors: KINDNESS G. , LONG W.F. , WILLIAMSON F.B. 
Published: July 2012

Anticoagulant activity of dermatan sulphates is unaffected by antiserum specific for antithrombin III (AT III) unless the glycosaminoglycan preparation contains demonstrable heparin.
Only dermatan sulphate preparations of considerable heparin content potentiate AT III inhibition of thrombin, factor Xa and plasmin.
These data suggest that dermatan sulphates exert anticoagulant activity which, unlike that of heparin, is largely or totally independent of AT III.
EFFECTS OF INFLAMMATORY AGENTS ON ENDOTHELIAL LYSOSOMAL FRAGILITY AND THEIR INHIBITION BY ANTIINFLAMMATORY DRUGS
Authors: YOFFE JOAN R. 
Published: July 2012

Endothelial cells from human unbilical veins were maintained in tissue culture. The fragility of lysosomal membranes were studied by microdensitometry.
Histamine (50 μm to 10 mm), 4‐methylhistamine (100 nm to 10 mm) and dimaprit (100 nm to 10 mm) increased lysosomal fragility. 2‐Thiazolyethylamine and 2‐pyridylethylamine (100 nm to 10 mm) had no effect.
Prostaglandins E1 and E2 (3 nm to 30 μm) and prostaglandin F2α (2 nm to 20 μm) had no direct effect. Low concentrations of prostaglandins E1 and E2 inhibited the fragility induced by histamine 100 μm.
Bradykinin (100 nm to 100 μm) decreased fragility.
The increase in fragility induced by histamine 100 μm or dimaprit 100 μm was inhibited by cimetidine (100 μm and 1 mm) but not by mepyramine (1 μm to 1 mm).
Pretreatment with indomethacin, hydrocortisone, ibuprofen and sodium salicylate caused a dose‐dependent inhibition of histamine‐induced fragility. Threshold concentrations were 1 pm, 100 pm, 10 nm and 10 μm, respectively.
Lignocaine (1 μm to 1 mm) had no direct effect and did not decrease histamine‐induced fragility.
CAPTOPRIL AND THE MAINTENANCE OF BLOOD PRESSURE AFTER SINOAORTIC DENERVATION IN THE RABBIT
Authors: PETTY MARGARET A. , REID J.L. 
Published: July 2012

At a dose of 1 mg/kg intravenously, captopril lowered blood pressure in conscious rabbits, that had undergone denervation of sinoaortic baroreceptors, but had no effect on heart rate. In sham‐operated controls, this dose caused only an increase in heart rate.
In the same experiments, captopril caused a substantial inhibition of plasma angiotensin converting enzyme (CE) activity of rapid onset and gradual decline over 2 to 3 h. The time course of recovery of blood pressure and plasma CE activity were similar.
Saralasin, by intravenous infusion, lowered blood pressure in sinoaortic rabbits but to a smaller extent than captopril.
The fall in blood pressure observed after captopril is not dependent on the integrity of baroreceptor afferents.
THE ACTION OF DANTROLENE SODIUM ON RAT FAST AND SLOW MUSCLE in vivo
Authors: LESLIE G.C. , PART N.J. 
Published: July 2012

Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a carrier solution of 5% mannitol taken to pH 10 with NaOH. This carrier solution itself was without effect on extrafusal muscle contraction.
Dantrolene sodium (5 mg/kg) had a greater depressant action on the twitch contraction of the fast extensor digitorum longus (EDL) muscle than on the slow soleus (SOL) muscle. The EDL twitch was depressed to 25.9% ± 1.2% (mean + s.e. mean, n = 7) of control whereas the SOL twitch was depressed to 31.3% ± 0.4% (n = 9). These values are significantly different at the P<0.001 level.
The twitch contraction time to peak was reduced by approximately 35% in both EDL and SOL by dantrolene sodium. However, the drug reduced the half relaxation time of SOL by approximately 30% but that of EDL was hardly affected.
The effect of dantrolene sodium on contractions elicited by repetitive stimulation was dependent upon the stimulation frequency. For the SOL muscle the greatest depression was produced at a stimulation frequency of 25 Hz and for EDL at 75 Hz. The minimum of depression was produced for a full fused tetanus for both muscles.
The significance of these findings is discussed in terms of the action of dantrolene sodium on motor control in the intact animal.
ARACHIDONIC ACID METABOLISM AND MODULATION OF in vitro ANAPHYLAXIS BY 5,8,11,14‐EICOSATETRAYNOIC ACID AND 9a,12a‐OCTADECADIYNOIC ACID
Authors: HITCHCOCK MARGARET , KOKOLIS NICHOLAS A. 
Published: July 2012

5,8,11,14‐Eicosatetraynoic acid (ETYA) inhibited the antigen‐induced contractions of tracheal spirals obtained from actively sensitized guinea‐pigs. Consistent data were obtained only when the spirals were treated with indomethacin.
ETYA did not affect histamine‐induced contractions of indomethacin‐treated tracheal spirals.
9a, 12a‐Octadecadiynoic acid (Ro‐3–1314) a potential inhibitor of linoleic acid metabolism, stimulated the antigen‐induced contraction of guinea‐pig tracheal spirals and the immunological release of slow reacting substance of anaphylaxis (SRS‐A) from actively sensitized guinea‐pig lung fragments.
Both ETYA and Ro‐3–1314 inhibited the immunological release of malondialdehyde from guinea‐pig lung fragments.
The data indicate that the effects of ETYA were due to inhibition of lipoxygenase and the effects of Ro‐3–1314 were due to inhibition of cyclo‐oxygenase.
The results suggest that products of lipoxygenase contribute to the antigen‐induced contraction of guinea‐pig lung, particularly when cyclo‐oxygenase is inhibited. Under these conditions there may be redirection of the metabolism of arachidonic acid to favour production of constrictor products of lipoxygenase such as SRS‐A.