bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECTS OF BRADYKININ AND THE BRADYKININ POTENTIATING PEPTIDE BPP5a ON THE ELECTRICAL AND MECHANICAL RESPONSES OF THE GUINEA‐PIG TAENIA COLI
Authors: AARSEN P.N. 
Published: July 2012

By means of the double sucrose‐gap technique, the effects of bradykinin and the bradykinin potentiating peptide BPP5a were compared on the guinea‐pig taenia coli under a number of experimental conditions.
In normal Krebs solution the response to bradykinin was mostly a slight stimulation, characterized by a depolarization, an increase in spontaneous spike activity and a contraction. If BPP5a caused any effect at all, it was stimulation of the spike activity but without depolarization. Since the effect of bradykinin was little affected by an increase in dose, a potentiating effect of BPP5a could not be determined.
Spontaneous spikes with a 5 to 7 s rhythm and prepotentials at their base were inhibited by bradykinin, whereas they were stimulated by BPP5a.
Oscillatory potentials (slow waves) induced by a calcium and magnesium‐free medium were also suppressed by bradykinin and stimulated by BPP5a. This effect of bradykinin was accompanied by a depolarization and a decrease in membrane resistance, phenomena not found after administration of BPP5a.
The amplitude of spontaneous spikes induced by potassium‐depolarization was suppressed by bradykinin, even though the membrane resistance and potential had been decreased. BPP5a produced either no effect or a small stimulatory effect without influencing the membrane resistance.
Reduction of the calcium concentration to 0.25 mM enhanced the stimulatory responses to both bradykinin and BPP5a, especially the spike activity and depolarization. In this case the membrane resistance was increased by bradykinin as well as BPP5a. These effects, especially those of BPP5a, were inhibited by reduction of the sodium concentration to 15.5 mM. Reduction of the chloride concentration to 9.7 mM decreased rather than increased the stimulatory effects of both bradykinin and BPP5a. Under these conditions bradykinin did not decrease the membrane resistance.
Bradykinin can have both inhibitory and stimulatory effects on the taenia coli whereas BPP5a has only a stimulatory effect. Since under certain conditions both responses to bradykinin are accompanied by a sodium‐dependent depolarization and decrease in membrane resistance, not influenced by lanthanum to any extent, it is suggested that bradykinin induces an increase in sodium conductance of the membrane. Under all the conditions investigated, except in low calcium, BPP5a did not affect the membrane potential and resistance. Thus, the underlying cause of its stimulatory effect is probably different from that of bradykinin.
THE CONTRIBUTION OF PROSTAGLANDINS IN THE MUSCLE OF HUMAN ISOLATED SMALL INTESTINE TO NEUROGENIC RESPONSES
Authors: BENNETT A. , STOCKLEY HELEN L. 
Published: July 2012

In strips cut parallel to the longitudinal or circular muscle, indomethacin (2‐10 μg/ml) usually lowered the tone, thus probably accounting for the reduction of nerve‐mediated relaxations to electrical field stimulation.
In longitudinal muscle strips, indomethacin enhanced contractions which occurred during electrical stimulation, probably because tone fell, but antagonized after‐contractions. By contrast, in the circular muscle indomethacin reduced initial contractions but enhanced after‐contractions.
Prostaglandin E2 counteracted all of the effects of indomethacin in the longitudinal muscle and most of those in the circular muscle; prostaglandin F2α restored circular muscle tone.
The results suggest that prostaglandins affect the muscle directly and contribute to the regulation of tone. They may also mediate non‐cholinergic contraction in longitudinal muscle and suppress contractility in the circular muscle.
THE INFLUENCE OF VASOACTIVE SUBSTANCES ON BLOOD FLOW AND CONTRACTILE RESPONSES OF CAT GASTROCNEMIUS
Authors: HUDLICKA O. , REIT E. 
Published: July 2012

The effects of several vasoactive substances have been studied on blood flow and acetylochline‐induced contraction of the vascularly isolated gastrocnemius of the cat. All substances, including acetylcholine, were administered intra‐arterially to the muscle. Blood flow and contractile tension were monitored simultaneously.
All substances which increased blood flow, enhanced the contractile responses to acetylcholine; angiotensin, which decreased blood flow, attenuated them.
Histamine was typical of the vasodilators in doses up to 1 μg (9 nmol), but in a dose tenfold higher it produced only a small and transient increase in blood flow and little or no enhancement of the acetylcholine‐induced contractions. These paradoxical effects were brought about by that portion of the high dose of histamine which re‐entered the cat's systemic circulation.
The order of potency of the vasodilators was the same for their potentiating effect on the acetylcholine‐induced contractile responses as for their enhancing effect on muscle blood flow: bradykinin >histamine>papaverine>NaH2PO4 >KCl. Median effective doses (ED50s) determined only for bradykinin, histamine and papaverine were, respectively, 20.5, 49.8, and 3,352 pmol as potentiators, and 13.4, 199.8 and 85,000 pmol as vasodilators.
In general, the effect of a given vasoactive substance on the contractile response to acetylcholine was dose‐dependent and correlated well with its effect on muscle blood flow at the moment the acetylcholine was injected. Two important exceptions were, firstly, that the highest dose of papaverine was only moderately effective as a potentiator even though highly effective as an increaser of muscle blood flow; and, secondly, that histamine produced its greatest potentiating effect 10 s after it was injected, at which time its effect on muscle blood flow was quite small.
It is suggested that these exceptions and, indeed, the much greater potentiating effectiveness of histamine and bradykinin versus papaverine may be due to the ability of histamine and bradykinin to increase the permeability of the muscle's capillaries as well as increasing blood flow through them, thus facilitating much better than mere vasodilators the access of bloodborne acetylcholine to its receptors on the muscle fibres.
THE ROLE OF EXTRACELLULAR CALCIUM IN THE CONTRACTIONS PRODUCED BY ACETYLCHOLINE IN CHRONICALLY DENERVATED MUSCLE
Authors: HALL MOIRA T. , MALEQUE M.A. , WADSWORTH R.M. 
Published: July 2012

Acetylcholine‐induced contractions of the isolated chronically denervated soleus muscle of the mouse consist of two phases, but both phases are equivalent to the contracture phase seen in vivo.
Low [Ca2+]o (0.5‐1.5 mM) augmented peak tension, as well as the rate of relaxation, of the first phase, but inhibited the second phase. Ethyleneglycol‐bis‐(β‐aminoethyl ether)‐N,N'‐tetraacetic acid (EGTA) or La3+ (2 mM) also inhibited the second phase, but not the first.
It was concluded that the first phase requires Ca2+ release from the sarcoplasmic reticulum, and is terminated by inactivation of the contractile process. The second phase is caused by the entry of activator Ca2+ from the extracellular space.
Increasing [Ca2+]o to 5 or 10 mM after the addition of acetylcholine caused a contraction, starting after a delay of about 50 seconds. EGTA or La3+ added during the second phase of the acetylcholine contraction caused relaxation after a much shorter lag time.
It is concluded that most of the Ca2+ entering from the extracellular fluid is taken up by the sarcoplasmic reticulum.
The acetylcholine second phase was augmented in low (25 mM) [Na+]o. It is concluded that Na+ and Ca2+ compete for the acetylcholine controlled ionic channels.
Isolated chronically denervated diaphragm muscles were less sensitive to acetylcholine and the contraction usually consisted of a first phase only.
It is concluded that sequestration of Ca2+ entering from the extracellular fluid is more complete in the diaphragm.
COMPARATIVE POTENCIES OF AMPHETAMINE, FENFLURAMINE AND RELATED COMPOUNDS IN TASTE AVERSION EXPERIMENTS IN RATS
Authors: BOOTH D.A. , PILCHER C.W.T. , D'MELLO G.D. , STOLERMAN I.P. 
Published: July 2012

Rats failed to drink a flavoured solution when its consumption had been followed by injection of amphetamine (conditioned taste aversion).
There was very little difference between the potencies of (+)‐ and (‐)‐amphetamine.
p‐Chloromethamphetamine was a more potent aversive agent than methamphetamine.
Strong taste aversions were also conditioned with other congeners of amphetamine. The rank order of potency was: fenfluramine > chlorphentermine >p‐hydroxyamphetamine.
Cocaine induced only moderate taste aversions, even at high doses.
Aversive potency did not appear to be correlated with known neurochemical actions of the drugs or with behavioural stimulation, but appeared to be a central action which may have been linked to anorexigenic potency or time course of action.
PROSTAGLANDIN F2α REDUCES THE ALGESIC EFFECT OF BRADYKININ BY ANTAGONIZING THE PAIN ENHANCING ACTION OF ENDOGENOUSLY RELEASED PROSTAGLANDIN E
Authors: JUAN H. , LEMBECK F. 
Published: July 2012

The isolated perfused ear of the rabbit connected to the body only by its nerve, was used to investigate the influence of prostaglandin F2α on the algesic effect of bradykinin and acetylcholine.
Bradykinin and acetylcholine, following intra‐arterial injection into the isolated perfused ear elicited a dose‐related reflex fall in blood pressure due to stimulation of paravascular pain receptors (=algesic effect).
Infusion of prostaglandin F2α (0.1 to 1 ng/ml) into the rabbit ear reduced the algesic effect of bradykinin but not that of acetylcholine.
The onset of the reflex fall in blood pressure by bradykinin but not that by acetylcholine was delayed by infusion of prostaglandin F2α into the ear.
Infusion of prostaglandin E1 into the rabbit ear led to an enhancement of the algesic effect of bradykinin and acetylcholine. Enhancement of both effects was abolished by infusion of prostaglandin F2α.
During inhibition of the endogenous synthesis of prostaglandins (mainly E‐type) by indomethacin, a low concentration of prostaglandin F2α no longer reduced the algesic effect of bradykinin. However, a high concentration of F2α continued to enhance the effect of bradykinin and acetylcholine.
Prostaglandin F2α influenced neither the brief reduction in venous outflow produced by bradykinin nor the brief increase in venous outflow caused by acetylcholine.
The results suggest that prostaglandin F2α does not directly reduce the effect of bradykinin but inhibits the enhancement of its algesic effect produced by prostaglandin E that is released endogenously by bradykinin. That the algesic effect of acetylcholine is not reduced by prostaglandin F2α is in keeping with its releasing very little endogenous prostaglandin E.
BRAIN AND VASCULAR MONOAMINE OXIDASE ACTIVITY IN THE DEOXYCORTICOSTERONE‐SALT HYPERTENSIVE RAT
Authors: LAI F.M. , SPECTOR S. 
Published: July 2012

The role of monoamine oxidase (MAO) in the maintenance of deoxycorticosterone‐sodium chloride (DOCA‐salt) hypertension was investigated by assaying the MAO activity both in central as well as peripheral blood vessels and in brain tissue.
The results suggest that the activity of MAO in the DOCA‐salt hypertensive rat is similar to the activity present in the normotensive rat.
EFFECTS OF D‐600 AND ITS OPTICAL ISOMERS ON FORCE OF CONTRACTION IN CAT PAPILLARY MUSCLES AND GUINEA‐PIG AURICLES
Authors: LUDWIG C. , NAWRATH H. 
Published: July 2012

(−)‐D‐600 and (+)‐D‐600 exerted concentration‐dependent negative inotropic effects in papillary muscles from cats, the potency of (−)‐D‐600 being about 100 times greater than that of (+)‐D‐600. The action was more pronounced at high than at low frequencies of stimulation. Time to peak force, relaxation time and therefore also total duration of contraction were not significantly affected by the drugs.
The negative inotropic effects of both drugs were not reversible after washing in drug‐free solution for 60 min at all concentrations tested.
The same negative inotropic effects were seen in guinea‐pig left auricles with the racemic mixture of both isomers.
Uptake measurements of D‐600‐[nitrile‐14C] in isolated left auricles of guinea‐pigs showed the drug to be accumulated in the myocardial tissue; tissue‐medium ratios from 1.25 to 6.0 were found at exposure times from 1 to 100 minutes. Preparations which were loaded first with D‐600‐[nitrile‐14C] for 100 min and then washed in drug‐free solution for different times lost up to about 80% of the initial radioactivity, whereas the depression of force of contraction was not reversible.
The results show that there are marked quantitative differences between the actions of (−)‐D‐600 and (+)‐D‐600 on isometric force of contraction in cat papillary muscles. Although the time course of the uptake of D‐600‐[nitrile‐14C] and the development of the negative inotropy in guinea‐pig left auricles were reasonably well related, the magnitude of the negative inotropy does not seem to be dependent on the total tissue concentration once the negative inotropic effect has been fully developed.
INHIBITION BY GLUCOCORTICOIDS OF PROSTAGLANDIN RELEASE FROM ADIPOSE TISSUE in vitro
Authors: CHANG J. , LEWIS G.P. , PIPER PRISCILLA J. 
Published: July 2012

When rabbit chopped adipose tissue was incubated with a lipolytic agent (adrenocorticotrophic hormone, ACTH1–24, 0.1 μg/ml) in Krebs solution, prostaglandin E2 was formed in the tissue and about the same amount was found in the medium.
In the presence of indomethacin (1 μg/ml) the appearance of prostaglandin E2 was almost abolished both in the tissue and in the medium.
When the incubation was carried out in the presence of hydrocortisone or betamethasone (1–10 μg/ml) the concentration of prostaglandin E2 leaking or carried into the medium was significantly reduced, whereas that remaining in the tissue was significantly increased. This action of the steroids was not reversed by increasing substrate (arachidonic acid) concentration in the medium.
The steroids did not affect lipolysis, nor did they influence prostaglandin metabolism since such activity was not detectable in the adipose tissue.
Anti‐inflammatory steroids therefore did not reduce prostaglandin formation but increased the tissue/medium ratio, which supports the view that they inhibit the release of prostaglandins after these have been synthesized.
BEHAVIOURAL AND PHARMACOKINETIC STUDIES IN THE MONKEY (Macaca mulatta) WITH DIAZEPAM, NORDIAZEPAM AND RELATED 1,4‐BENZODIAZEPINES
Authors: CURRY S.H. , WHELPTON R. , NICHOLSON A.N. , WRIGHT CATHERINE M. 
Published: July 2012

Behavioural activity (delayed differentiation and spatial delayed alternation) and pharmacokinetics of diazepam and its metabolites, N‐desmethyldiazepam (nordiazepam), 3‐hydroxydiazepam (temazepam) and 3‐hydroxy‐N‐desmethyldiazepam (oxazepam), and of dipotassium clorazepate (clorazepate), were studied in the monkey (Macaca mulatta). Diazepam and its metabolites (1.8 and 3.0 mg/kg) and clorazepate (2.6 and 4.3 mg/kg) were given by intraperitoneal injection.
Hydroxylation of diazepam (temazepam and oxazepam) led to a loss of, or a considerable reduction in, behavioural activity, whereas activity was preserved, though modified, by demethylation (nordiazepam). It was not possible to establish change in behaviour at specific time intervals after clorazepate, but combined performance data revealed an effect.
The maximum mean plasma concentrations of diazepam, temazepam, oxazepam and clorazepate were observed at 0.5 h, and the maximum mean plasma concentration of nordiazepam was observed at 1 hour. Plasma concentrations of nordiazepam were the highest and decreased monoexponentially. Plasma concentrations of the other drugs declined rapidly at first but more slowly later, and these data were analysed as biexponential models. In the analysis for metabolites, nordiazepam reached measurable levels after the injection of diazepam and clorazepate.
It is suggested that differences in the effects of closely related benzodiazepines may not be due solely to their plasma pharmacokinetic properties, but may arise from differences in their intrinsic activity.
A PRESYNAPTIC SITE OF ACTION WITHIN THE MESENCEPHALIC RETICULAR FORMATION FOR (+)‐AMPHETAMINE‐INDUCED ELECTROCORTICAL DESYNCHRONIZATION
Authors: CANDY J.M. , KEY B.J. 
Published: July 2012

Changes induced in the electrocorticogram by the bilateral perfusion of (+)‐amphetamine into the mesencephalic reticular formation (MRF) have been studied in cat encéphale isolé preparations.
(+)‐Amphetamine, applied for 5 min in the MRF, mimicked the electrocortical desynchronization induced by the perfusion of (−)‐noradrenaline (NA) or (−)‐α‐methylnoradrenaline (AMNA) into the same sites.
Perfusion of 6‐hydroxydopamine (6‐OHDA) also induced desynchronization but, over the 1 h perfusion period, slow wave activity gradually returned to the electrical record.
Following the application of 6‐OHDA the effect of (+)‐amphetamine was abolished or significantly attenuated, whereas the effect of NA or AMNA was not affected.
The electrocortical desynchronization induced by (+)‐amphetamine could be restored if its application was preceded by perfusion with NA or AMNA.
Fluorescence studies using AMNA indicated that 6‐OHDA depleted noradrenergic nerve terminals near the cannulae tips. However, the terminals were still capable of taking up exogenously applied AMNA.
These results suggest that (+)‐amphetamine has a presynaptic action on noradrenergic nerve terminals within the MRF.
ENKEPHALINS AND DORSAL HORN NEURONES OF THE CAT: EFFECTS ON RESPONSES TO NOXIOUS AND INNOCUOUS SKIN STIMULI
Authors: DUGGAN A.W. , HALL J.G. , HEADLEY P.M. 
Published: July 2012

In spinal cats anaesthetized with α‐chloralose, a study was made of the effects of methionine enkephalin and methionine enkephalin amide on the responses of neurones of spinal laminae IV and V to noxious and innocuous skin stimuli. The enkephalins were ejected from micropipettes either in the region of cell bodies or in the substantia gelatinosa.
Administered near cell bodies the enkephalins reduced spontaneous firing and cell responses to both types of skin stimuli. These effects were antagonized by naloxone when administered near cell bodies but not when given intravenously in doses (0.3‐0.6 mg/kg) more than adequate to antagonize analgesic doses of morphine.
Administered in the substantia gelatinosa the enkephalins were more selective in their action. The predominant effect was a reduction in nociceptive responses with little effect on non‐nociceptive responses although spontaneous firing was commonly reduced. Naloxone administered either in the substantia gelatinosa or intravenously (0.1‐0.3 mg/kg) reversed these effects of the enkephalins.
SOME EFFECTS OF PROSTAGLANDINS E1 AND E2 AND OF ENDOTOXIN INJECTED INTO THE HYPOTHALAMUS OF YOUNG CHICKS: DISSOCIATION BETWEEN ENDOTOXIN FEVER AND THE EFFECTS OF PROSTAGLANDINS
Authors: ARTUNKAL AKGÜL A. , MARLEY E. , STEPHENSON J.D. 
Published: July 2012

Prostaglandins E1 and E2 elevated body temperature of young chicks when injected into the hypothalamus at thermoneutrality (31°C). In contrast, they lowered body temperature when so injected below thermoneutrality (16°C): the relation of the fall in body temperature to increased heat loss and decreased heat production was examined.
The above effects below thermoneutrality were potentiated by pretreatment with inhibitors of prostaglandin synthetase and possible reasons for this potentiation are given.
The ‘O’‐somatic antigen of Shigella dysenteriae consistently evoked hyperthermia when injected into the hypothalamus, irrespective of whether the chicks were within or below thermoneutrality.
Pretreatment with prostaglandin synthetase inhibitors failed to prevent the onset of endotoxin fever; however, duration of the fever, induced by intrahypothalamic injection of the O‐somatic antigen of Shigella dysenteriae was reduced.
The intrahypothalamic injection, below thermoneutrality of prostaglandins E1, E2, noradrenaline, 5‐hydroxytryptamine or carbachol reversed endotoxin fever, inducing even substantial falls in body temperature.
While the results cast some doubts on the role of prostaglandins of the E series as mediators of endotoxin fever in chicks, they cannot be eliminated as mediators until the significance of the reduction in duration of the pyrexic response by indomethacin and 5,8,11,14‐eicosatetraynoic acid, and the degree of synthesis inhibition attained, are known.
PHARMACOLOGICAL AND CERTAIN CHEMICAL PROPERTIES OF AH 10407, AN UNUSUALLY SHORT‐ACTING, COMPETITIVE NEUROMUSCULAR BLOCKING DRUG, AND SOME RELATED COMPOUNDS
Authors: BRITTAIN R.T. , JACK D. , TYERS M.B. 
Published: July 2012

1,1′‐Azobis[3‐methyl‐2‐phenylbenzimidazolinium]dimethanesulphonate(AH 10407) has an ultrashort, competitive neuromuscular blocking action in the mouse, cat, dog, Cynamolgus monkey and cotton‐eared marmoset.
AH 10407 is chemically unstable in bicarbonate‐containing solutions and is degraded to inactive products. The half‐life of AH 10407 in vitro in dog and human whole blood and in Krebs physiological solution is about 1.0 minute. In distilled water and in HCO3‐deficient Krebs solution AH 10407 is much more stable. Base catalyzed degradation is shown to be the prime determinant of the duration of action of the drug.
Some pharmacological properties of AH 11244 and AH 11056, close analogues of AH 10407, are briefly described and the duration of their neuromuscular blocking actions rationalized by reference to their chemical stabilities.
THE ENHANCEMENT OF CHLORPROMAZINE‐INDUCED HYPOTHERMIA BY LESIONS IN THE ANTERIOR HYPOTHALAMUS
Authors: CHAI C.Y. , LIN M.T. 
Published: July 2012

Administration of chlorpromazine (Cpz), either systemically or centrally, to unanaesthetized rats at an environmental temperature of 23 °C caused dose‐dependent hypothermia.
In order to achieve equivalent hypothermia, intraventricular administration required a total dose of 20 μg Cpz and intraperitoneal administration a dose of 9.7 mg/kg body weight. Accordingly, the dose‐ratio between intraventricular and intraperitoneal administration was 1 to 110. Cpz apparently exerts its hypothermic effect by acting directly on central nervous structures rather than through peripheral sites.
Cpz‐induced hypothermia was potentiated by preoptic anterior hypothalamic (POAH) lesions but not by lesions of the ventromedial nucleus (VMN) of the hypothalamus. It was found that Cpz induced hypothermia most readily in rats with large POAH lesions (‐10.4°C), less so in rats with spinal lesions (‐ 5.5°C) at least with control rats (‐ 2.9°C).
COMPARATIVE INHIBITORY EFFECTS OF 3‐QUINUCLIDINYL BENZILATE (QNB) AND ATROPINE ON AMYLASE RELEASE FROM RAT PANCREAS
Authors: MORISSET J. , NG K.H. , POIRIER G.G. 
Published: July 2012

Secretion of amylase from rat pancreas stimulated by urecholine was studied in relation to its inhibition by atropine and 3‐quinuclidinyl benzilate (QNB).
Urecholine‐induced secretion was completely abolished by atropine at 10−6 M and QNB at 10−8 M. Significant inhibition could be detected at 10−8 M atropine and 10−10 M QNB.
The secretory response to pancreozymin was not blocked either by atropine or QNB.
The inhibitory effect of QNB remained for at least 90 min after its removal from the incubation medium.
It is concluded that QNB is 10 times more potent than atropine in inhibiting pancreatic amylase secretion induced by urecholine.