bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE IONIZATION OF MORPHINE, HYDROXY AMPHETAMINE AND (+)‐TUBOCURARINE CHLORIDE AND A NEW METHOD FOR CALCULATING ZWITTERION CONSTANTS
Authors: BARLOW R.B. 
Published: July 2012

An improved method for estimating the zwitterion constants of phenolic amines is described which involves the exploratory least‐squares fit of absorbance (at a suitable wavelength) to pH, starting with estimates of pK1 and pK2 obtained electrometrically.
With the method it is possible to see that hydroxyamphetamine (α‐methyltyramine) has a higher zwitterion constant than tyramine and the zwitterion constants of both compounds are lower at 37°C than at 25°C.
The zwitterion constant of morphine is not reduced by raising the temperature from 25° to 37°C and the effect of temperature is much greater in compounds with a primary or secondary amino group than with those containing a tertiary amino group. Some zwitterions may be stabilized by hydration and their formation will be reduced by a rise in temperature which will break up water structure.
From electrometric titrations with (+)‐tubocurarine chloride in 0.1 m NaCl estimates of pK1, pK2 and pK3 were 7.6, 8.65 and 9.65 at 25°C and 7.4, 8.6 and 9.7 at 37°C, compared with 7.8, 8.85 and 9.75 given by Perrin (1980). However, the effects of pH on absorbance show that the phenolic groups lose a proton before the ammonium group so there is extensive zwitterion formation which is probably greater at 25° than at 37°C. The p‐phenolic group (position 13) probably ionizes first with the phenate form stabilized by hydration involving water molecules and the protonated form of the (1‐) ammonium group.
THE EXISTENCE OF A NEW SUBTYPE OF α‐ADRENOCEPTOR ON THE RAT ANOCOCCYGEUS IS REVEALED BY SGD 101/75 AND PHENOXYBENZAMINE
Authors: COATES JILL , JAHN U. , WEETMAN D.F. 
Published: July 2012

Noradrenaline and Sgd 101/75 (4(2‐imidazoline‐amino)‐2‐methylindazol‐chlorhydrate) acted as full agonists in contracting the rat anococcygeus.
Very low concentrations of phenoxybenzamine (0.3 nm for 2–30 min) reduced preferentially the effects of Sgd 101/75. Preparations made insensitive to Sgd 101/75 by phenoxybenzamine still contracted to noradrenaline, this contraction occurring in the presence of high concentrations (400 μm) of Sgd 101/75.
It is concluded therefore that the α1‐adrenoceptor in this preparation is not a homogeneous entity and must be subdivided into at least two subtypes.
EFFECT OF CONVERTING ENZYME INHIBITION ON THE RENAL HAEMODYNAMIC RESPONSES TO NORADRENALINE INFUSION IN THE RAT
Authors: ARUNDELL LEWIS A. , JOHNS EDWARD J. 
Published: July 2012

The renal haemodynamic responses to a close arterial infusion of noradrenaline (29.7–177.9 nmol kg−1h−1) were measured in rats anaesthetized with pentobarbitone. Systemic blood pressure was unaffected by noradrenaline infusion at this dose level. Renal blood flow was significantly reduced by 16% while glomerular filtration rate remained unchanged. These responses resulted in a rise in filtration fraction of some 10%.
In a separate group of animals, noradrenaline infusion in this manner and at a similar dose rate increased plasma renin activity approximately 3 fold.
Continuous infusion of the angiotensin converting enzyme inhibitor, teprotide (3.36 μmol kg−1h−1), had no measurable effect on systemic blood pressure, renal blood flow, glomerular filtration rate or filtration fraction.
Infusion of noradrenaline into these animals receiving teprotide caused a significant fall in renal blood flow of 16%. There was a fall in glomerular filtration rate of some 17% which was significantly different from the response observed in the animals not receiving teprotide. There was a consequent small but insignificant fall in filtration fraction.
These data show that the regulation of glomerular filtration rate in response to the vasoconstrictor drug, noradrenaline, is partly mediated via the renin‐angiotensin system. They provide evidence for a role of intrarenal angiotensin II in regulating glomerular filtration by causing efferent arteriolar vasoconstriction.
KININS STIMULATE NET CHLORIDE SECRETION BY THE RAT COLON
Authors: CUTHBERT ALAN W. , MARGOLIUS HARRY S. 
Published: July 2012

Short circuit current (SCC), transepithelial conductance and ion fluxes were measured across the isolated descending colon of the rat in response to bradykinin or kallidin.
Kinins added to the serosal bath caused immediate increases in SCC but were ineffective when added to the mucosal bath. Increases in SCC were accompanied by significant increases in transepithelial conductance. Threshold kinin concentration was 0.5 nm and maximal increases were seen at 50–100 nm.
A rat glandular kallikrein (7 nm) or mellitin (2 μm) also increased SCC if added to the serosal bath.
Responses to kinins were unaffected by mucosal amiloride (100 μm) but attenuated or blocked by serosal frusemide (100 μm), indomethacin (1 μm) or mepacrine (50 μm).
Replacement of chloride ion in the serosal bath by gluconate and sulphate ions abolished responses to kinins which reappeared after chloride re‐addition.
Measurement of 36Cl, 22Na and 86Rb fluxes across the tissue showed that the kinin‐induced increase in SCC resulted principally from increased net chloride secretion. Effects upon 22Na or 86Rb flux were minimal and made no contribution to the current responses observed in this tissue.
The results prove that kinins stimulate net chloride secretion in the rat colon, most probably via a prostaglandin‐dependent pathway.
LIDOFLAZINE IN THE EARLY STAGES OF ACUTE MYOCARDIAL ISCHAEMIA
Authors: COKER SUSAN J. , FAGBEMI O. , PARRATT J.R. 
Published: July 2012

Pretreatment of anaesthetized rats with intravenously administered lidoflazine (an antianginal agent) reduced the incidence and severity of ventricular arrhythmias which resulted from acute coronary artery ligation. Ventricular fibrillation was completely prevented by doses of 50 μg/kg and 2 mg/kg and no animal so treated died (contrast 50% incidence of fibrillation in the controls and 30% mortality).
In anaesthetized greyhound dogs, lidoflazine (2 mg/kg) administration resulted in transient reductions in systemic arterial pressure, LV dP/dt max and cardiac output. Coronary sinus PO2 was markedly increased, indicating pronounced coronary vasodilatation.
Lidoflazine pretreatment inhibited the increase in epicardial ST‐segment elevation which resulted, in dogs, from short (3 min) occlusions of the left anterior descending coronary artery. This effect was especially marked at sites where, in control occlusions, ST‐segment elevation was most pronounced.
Lidoflazine greatly reduced the number of ventricular ectopic beats which usually resulted from more prolonged (30 min) periods of acute coronary artery occlusion. There was no ventricular fibrillation in these dogs (contrast 25% incidence in the controls).
Lidoflazine did not modify the ventricular fibrillation which results from reperfusion of a previously ischaemic area of the left ventricular wall.
EVIDENCE FOR AN A2/Ra ADENOSINE RECEPTOR IN THE GUINEA‐PIG TRACHEA
Authors: BROWN C.M. , COLLIS M.G. 
Published: July 2012

An attempt was made to determine whether the extracellular adenosine receptor that mediates relaxation in the guinea‐pig trachea is of the A1/Ri or A2/Ra subtype.
Dose‐response curves to adenosine and a number of 5′‐ and N6‐substituted analogues were constructed for the isolated guinea‐pig trachea, contracted with carbachol.
The 5′‐substituted analogues of adenosine were the most potent compounds tested, the order of potency being 5′‐N‐cyclopropylcarboxamide adenosine (NCPCA) > 5′‐N‐ethylcarboxamide adenosine (NECA) > 2‐chloroadenosine > l‐N6‐phenylisopropyladenosine (l‐PIA) > adenosine > d‐N6‐phenylisopropyladenosine (d‐PIA).
The difference in potency between the stereoisomers d‐ and l‐PIA on the isolated trachea was at the most five fold.
Responses to low doses of adenosine and its analogues were attenuated after treatment with either theophylline or 8‐phenyltheophylline. The responses to 2‐chloroadenosine were affected to a lesser extent than were those to the other purines.
Adenosine transport inhibitors, dipyridamole and dilazep, potentiated responses to adenosine, did not affect those to NCPCA, NECA, l‐PIA and d‐PIA but significantly reduced the responses to high doses of 2‐chloroadenosine.
Relaxations evoked by 9‐β‐d‐xylofuranosyladenosine which can activate intracellular but not extracellular adenosine receptors, were attenuated by dipyridamole but unaffected by 8‐phenyltheophylline.
The results support the existence of an extracellular A2/Ra subtype of adenosine receptor and an intracellular purine‐sensitive site, both of which mediate relaxation.
BLOOD FLOW, HISTAMINE CONTENT AND HISTIDINE DECARBOXYLASE ACTIVITY IN RAT SKIN GRAFTS AND THEIR MODIFICATION BY CYCLOSPORIN‐A
Authors: FAN T‐P.D. , LEWIS G.P. 
Published: July 2012

An attempt has been made to monitor simultaneously the changes in blood flow, histamine content, histidine decarboxylase (HDC) activity and mast cell population in rat skin isografts and allografts.
The histamine content in rat skin allografts during rejection was decreased in contrast with our earlier observation in rabbits.
Although no definite correlation has been found between blood flow changes, histamine content or HDC activity, a reciprocal relationship appeared to exist between histamine content and HDC activity in the skin grafts, which might be a reflection of the immunosuppressive activity of this amine.
The immunosuppressive agent, cyclosporin‐A (20 mg/kg daily) was able to prolong skin allograft survival and prevent the changes in histamine and HDC activity in allografts.
Possible implications of these findings are discussed in relation to current knowledge concerning the interactions between endothelial cells, lymphocytes and mast cells/basophils in graft rejection.
INFLUENCE OF N‐ETHYLMALEIMIDE ON CHOLINOCEPTORS AND RESPONSES IN LONGITUDINAL MUSCLES FROM GUINEA‐PIG ILEUM
Authors: ARONSTAM ROBERT S. , CARRIER GERALD O. 
Published: July 2012

The binding of carbamylcholine to membranes prepared from the longitudinal muscle of guinea‐pig ileum was determined from its inhibition of the binding of [3H]‐3‐quinuclidinyl benzilate. Carbamylcholine binding was resolved into high and low affinity components with apparent dissociation constants of 0.11 ± 0.02 and 11 ± 1 μm 42% of the receptors displayed high affinity carbamylcholine binding.
Alkylation of longitudinal muscle membranes with N‐ethylmaleimide increased muscarinic receptor affinity for carbamylcholine in a manner consistent with a conversion of low affinity to high affinity receptors. After exposure the muscle membrane fragments to 1 mm N‐ethylmaleimide for 20 min at 35°C, carbamylcholine binding was resolved into two components with apparent dissociation constants of 0.11 ± 0.01 and 9 ± 2 μm, with 74% of the receptors displaying the higher affinity.
Exposure of longitudinal membranes mounted in an organ chamber to 1 mm N‐ethylmaleimide for 30 s depressed isometric contractions in response to acetylcholine by 80%, while contractions induced by K+ and Ba2+ were reduced by less than 20% and 10%, respectively. Acetylcholine dose‐response curves were shifted to the right while Ba2+ curves were unaffected.
It is suggested that N‐ethylmaleimide has a selective effect on muscarinic responses in the longitudinal muscle by disrupting processes occurring after receptor occupancy but before the induction of phospholipid turnover or calcium influx in the postsynaptic membrane.
INHIBITION OF IONIC CURRENTS IN FROG NODE OF RANVIER TREATED WITH NALOXONE
Authors: CARRATU' MARIA R. , MITOLO‐CHIEPPA DELIA 
Published: July 2012

Myelinated nerve fibres of frog sciatic nerve were investigated under current and voltage clamp conditions. In the presence of 68 μM external naloxone, the action potential was completely, though progressively, blocked within 15 min of drug superfusion. The resting potential remained constant.
Under voltage clamp conditions both peak Na+ and steady‐state K+ currents were decreased reversibly by external naloxone. Both currents were reduced in a dose‐dependent manner but, whereas sodium current was affected by the smallest concentrations of naloxone (1.3 up to 12.5 μm), potassium current was decreased only by higher concentrations (25 up to 112 μm).
The time‐course of development of the effect on both Na+ and K+ currents after exposure to 112 μm naloxone (a concentration giving more than 50% of decrease) showed that the effect develops quickly within the first 2 min of exposure to the drug, but afterwards both currents continue to fall more slowly, though progressively.
Experiments with constant test pulses to Em = −10 mV and conditioning prepulses of various amplitudes, showed that the Na inactivation curve, h∞ (Em), was shifted in a negative direction along the potential axis; the shape of the curve was also slightly changed in the presence of naloxone since the shift was larger near the top of the curve. All the observed effects were reversible after returning to the standard Ringer solution.
Internal naloxone (< 0.2 mm) reduced the amplitude of the action potential as well as peak Na+ and steady‐state K+ currents; the sodium inactivation curve, h∞ (Em), was shifted to more negative potentials.
A possible anaesthetic‐like activity of naloxone on the nodal membrane is discussed.
The effect of magnesium deficiency and excess on bovine coronary artery tone and responses to agonists
Authors: Kalsner Stanley 
Published: July 2012

The hypothesis that magnesium deficiency, linked to the magnesium content of drinking water, induces major tone increases in coronary arteries and enhances their responses to vasoactive agents to an extent sufficient to explain sudden death associated with ischaemic heart disease was examined in an in vitro preparation.
The spontaneous tone of cattle coronary arteries was not increased during a 30 min exposure to Mg2+‐deficient Krebs until the mineral was omitted entirely from the bathing medium, and even then the observed increase was small. Only in strips maintained under extremely deficient conditions for a prolonged period, namely Mg2+ concentration of 0.2 mm and 0.0 mm for 3h, was tone substantially greater than in controls in standard (1.2 mm) Mg2+‐Krebs.
Responses to acetylcholine and to noradrenaline were not increased in Mg2+‐free Krebs but those to potassium and to 5‐hydroxytryptamine were enlarged over the lower parts of their concentration‐response curves. Responses to potassium and to 5‐hydroxytryptamine were also examined in Krebs containing very low concentration of Mg2+ (0.4 and 0.2 mm) and only modest increases in contraction size were detected. Increases in the Mg2+ concentration of the Krebs (to 4.8 mm) depressed responses to potassium and 5‐hydroxytryptamine.
It is concluded that Mg2+ deficiency must be nearly complete (0.4–0.0 mm) to induce even moderate tone increases in coronary vessels, or to sensitize them to agonist responses, and that there is no reason to link marginally subnormal Mg2+ levels, occasionally reported in humans with heart disease, to marked changes in coronary dynamics.
Additional evidence against universal modulation of β‐adrenoceptor responses by excessive thyroxine
Authors: Taylor Samuel E. 
Published: July 2012

The effect of prolonged, excessive thyroxine on β‐adrenoceptor‐mediated relaxation of guinea‐pig trachea was studied.
Thyroxine did not significantly affect the potency of the β1‐adrenoceptor agonist, noradrenaline, or the β2‐adrenoceptor agonist, terbutaline.
Thyroxine did not significantly affect the apparent KB values of the selective β1‐adrenoceptor antagonist, practolol, or the selective β2‐adrenoceptor antagonist, butoxamine.
Thyroxine did not significantly affect the maximum response to noradrenaline. The maximum response to terbutaline in tissues from the thyroxine‐treated animals was only slightly lower than the maximum response in tissues from paired control animals.
These results suggest that excessive thyroxine does not significantly affect the β‐adrenoceptor‐mediated relaxation of guinea‐pig trachea and that the reported modulation of β‐adrenoceptor‐mediated responses in other tissues is specific for the given tissue rather than common to all β‐adrenoceptor systems.
Anticonvulsant‐like actions of baclofen in the rat hippocampal slice
Authors: Ault Brian , Nadler J. Victor 
Published: July 2012

The effects of baclofen were tested on epileptiform discharge in the rat hippocampal slice. Slices were superfused with bicuculline methiodide (100 μm) and maximal periods of afterdischarge were evoked by stimulating the Schaffer collateral‐commissural pathway in area CA1, mossy fibres in area CA3 or perforant path fibres in the fascia dentata or by antidromic stimulation of CA1 pyramidal cells.
(−)‐Baclofen attenuated the afterdischarge evoked by stimulating all three sets of fibres in areas CA1 and CA3. In each case, a threshold effect was observed at a concentration of 0.25 or 0.5 μm, and complete suppression was usually attained with a concentration of 5 μm. EC50 values ranged between 1 and 2 μm. (−)‐Baclofen attenuated hippocampal afterdischarge with 120 times the potency of (+)‐baclofen. It did not, however, affect the repetitive firing of dentate granule cells in response to stimulation of perforant path fibres.
(−)‐Baclofen also reduced the amplitude of the initial population spike evoked by stimulation of Schaffer collateral‐commissural fibres, but did not affect the antidromic population spike nor the initial population spike evoked by stimulation of the mossy fibres.
Recurrent inhibition in area CA1 was abolished by 1 μm (−)‐baclofen. Thus baclofen, unlike many anticonvulsants, does not suppress afterdischarge by potentiating GABAergic inhibition.
These results suggest that baclofen attenuates hippocampal afterdischarge by a combination of pre‐ and postsynaptic mechanisms.
Comparison of the chronotropic effect and the cyclic AMP accumulation induced by β2‐agonists in rat heart cell culture
Authors: Freyss‐Beguin Marianne , Griffaton Geneviève , Lechat Paul , Picken Douglas , Quennedey Marie Claude , Rouot Bruno , Schwartz Jean 
Published: July 2012

The chronotropic response and the variation in cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) accumulation induced by isoprenaline and six β2‐selective agonists (fenoterol, salmefamol, soterenol, zinterol, salbutamol and formoterol) were analyzed on cultured heart cells of the rat.
The compounds elicited an enhancement of the frequency, but the time course of the variation of the beating rate was not identical for all of them. A rapid onset was observed for isoprenaline, zinterol and formoterol while it was slower for fenoterol, salmefamol and salbutamol.
In contrast with isoprenaline, the β2‐selective agonists gave concentration‐beating frequency curves which were not sigmoidal. Their effects extended up to a concentration of 5 to 6 orders of magnitude. Nevertheless, the concentration at which the maximal effect occurred and the intrinsic activities of the various compounds agrees better with the responses observed on guinea‐pig atria than with those on trachea.
All the β2‐selective agonists increased the accumulation of cyclic AMP in rat heart cells with a maximal effect at 10−5 m or less. The effects of β2‐agonists on cyclic AMP production showed some analogies with those on beating frequency of the heart cells. The increase in cyclic AMP accumulation induced by β2‐agonists also corresponded to their chronotropic effects on guinea‐pig atria. Thus, the correlation coefficient between the inverse of the log of the concentration producing the half maximal cyclic AMP accumulation in cultured heart cells and the pD2 values on guinea‐pig atria was 0.93.
It is concluded that, in contrast to what was observed in other models, the β2‐selective agonists induce an increase in the production of cyclic AMP in rat heart cells. Furthermore, the effects of the β2‐agonists on cyclic AMP accumulation and on beating rate in the heart cells may correspond with their β1‐adrenoceptor potencies.
Characterization of postsynaptic α‐adrenoceptors in rat aortic strips and portal veins
Authors: Digges K.G. , Summers R.J. 
Published: July 2012

Postsynaptic α‐adrenoceptors in rat isolated aortic strips and portal veins have been examined using a number of agonist and antagonist drugs which have varying selectivity for α1‐ and α2‐adrenoceptors.
In both tissues (−)‐noradrenaline ((−)‐NA), (−)‐adrenaline ((−) Adr) (−)‐α‐methyl noradrenaline ((−)‐α‐Me‐NA) and (−)‐phenylephrine ((−)‐PE) were full agonists, while clonidine, oxymetazoline and (2‐(2,6‐dichlorophenyl)‐5,6‐dihydroimidazo(2,1,b) thiazole (44,549) were partial agonists. Guanfacine was a full agonist in aortic strips but only a partial agonist in portal veins.
In aortic strips, pA2 values for prazosin and yohimbine were not significantly different using (−)‐NA, (−)‐PE or guanfacine as the agonist, suggesting a single population of α‐adrenoceptors. The order of potency of the antagonists, prazosin = 2‐(β‐(4‐hydroxyphenyl)‐ethylaminomethyl)‐tetralone (BE2254) > phentolamine > yohimbine > rauwolscine, is indicative of an α1‐type of receptor.
In portal veins, the order of potency of the antagonists was prazosin > BE2254 > phentolamine > yohimbine > rauwolscine, again indicating an α1‐type of receptor.
The mean pA2 value for yohimbine was not significantly different in either tissue. However, mean pA2 values for prazosin, BE‐2254 and phentolamine were approximately one order of magnitude lower in portal veins than in aortic strips, suggesting that the receptors in the two tissues may not be identical.
The role of 5‐hydroxytryptamine in the feline response to intravenous infusion of live E. coli
Authors: Arvidsson S. , Falk A. , Haglind E. , Haglund U. 
Published: July 2012

A standardized septic shock was induced in cats by intravenous infusion of a live E. coli bacteria strain. The bacterial infusion induced a rapid haemodynamic response characterized mainly by a pulmonary arterial hypertension and a late phase characterized by systemic hypotension and hypodynamic circulation.
Systemic arterial, pulmonary arterial, portal venous, left atrial pressures, max inspiratory‐expiratory pressure difference in the trachea, aortic and intestinal blood flows were monitored. Arterial blood samples were taken for recording the number of circulating platelets and white blood cells and for determining the acid‐base balance.
The effect of pretreatment with ketanserin, a specific 5‐hydroxytryptamine2 (5‐HT2)‐receptor blocker on these haemodynamic reactions was studied.
In short term experiments on non‐bacteriaemic control cats, ketanserin prevented the pulmonary hypertension induced by intravenous 5‐HT infusions but not the increase in intestinal blood flow.
Ketanserin induced a reduction of total peripheral (including intestinal) vascular resistance to blood flow but had no effect on aortic blood flow.
After infusion of bacteria, ketanserin pretreated cats were more hypotensive due to a relative peripheral dilatation of the resistance vessels. Ketanserin pretreatment had no effect on the pulmonary vascular reactions, the tracheal pressure difference or the number of circulating platelets or white blood cells. Thus, except for a more pronounced hypotension early after bacterial infusion, ketanserin pretreatment did not influence the haemodynamic response.
It is concluded that 5‐HT is not of significant importance in the pathogenesis of the haemodynamic reactions following experimental bacteraemia.