bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF Δ9‐TETRAHYDROCANNABINOL, 2.4‐DINITROPHENOL AND PENTOLINIUM TARTRATE ON BEHAVIOURAL THERMOREGULATION IN MICE
Authors: PERTWEE R.G. , TAVENDALE R. 
Published: July 2012

A new apparatus in which mice are allowed to shuttle between the warm and cool parts of a continuous oval tunnel has been designed for the measurement of drug effects on behavioural thermoregulation.
The length of time that untreated mice spent in the warmer part of the apparatus (tunnel wall temperature 38°C) was found to be inversely related to the temperature of the cooler part (wall temperature 18c, 24c or 30°C).
Mice treated with 2,4‐dinitrophenol at a dose known to be hyperthermic at an ambient temperature of 32 C (20 mg/kg s.c.) spent an increased length of time in the cooler part of the apparatus (wall temperature 18°C) and did not exhibit any change in rectal temperature.
Mice treated with pentolinium tartrate at a dose known to be hypothermic at room temperature (5.0 mg/kg i.v.) spent a decreased length of time in the cooler part of the apparatus (wall temperature 24 C) and did not exhibit any change in rectal temperature.
It is concluded from the above results that the apparatus can be used to measure drug effects on behavioural thermoregulation.
In experiments of 30 min duration, mice treated with Δ9‐tetrahydrocannabinol (A9‐THC) at doses known to be hypothermic and to lower oxygen consumption at room temperature (20 mg/kg i.p. or 2.0 mg/kg i.v.) spent a longer time in the warmer part of the apparatus between 15 and 30 min after injection. Rectal temperatures measured 30 min after injection were only slightly less than those of control mice. In these experiments the wall temperature of the cool tunnel was 24C.
In experiments of 15 min duration, mice treated with A9‐THC (20 mg/kg) and then placed in the apparatus spent more time in the cooler part of the apparatus (wall temperature 24 C) and exhibited a large fall in rectal temperature.
It is concluded that immediately after injection of A9‐THC the mice do not attempt to oppose drug‐induced falls in deep body temperature by moving into a warm environment and that only later do the animals demonstrate a preference for a warm environment.
POST‐TETANIC POTENTIATION IN GANGLIA WHICH ARE BLOCKED WITH HEXAMETHONIUM
Authors: CHRIST DARYL 
Published: July 2012

Post‐tetanic potentiation (p.t.p.) of the compound action potential in the presence of hexamethonium was observed in the isolated stellate ganglion of the hamster using extracellular postganglionic recordings.
The magnitude of the p.t.p. was small (less than a 20% increase) in the control solution, but increased as the depth of blockade with hexamethonium was increased.
The magnitude of the p.t.p. was frequency‐dependent between 1 and 40 Hz.
Atropine partially blocked the p.t.p.
McN‐A‐343, a muscarinic agonist, potentiated ganglionic transmission which had been partially blocked by hexamethonium.
Repetitive stimulation in the presence of hexamethonium potentiated the discharges induced by DMPP, a nicotonic agonist. The potentiation was blocked by atropine.
It was concluded that the p.t.p. in the presence of hexamethonium has the same characteristics as p.t.p. in the control solution. There appears to be both a muscarinic component and a presynaptic component of the p.t.p.
SELECTIVE INHIBITION OF THERMOGENESIS BY TRIBUTYL S,S,S,‐PHOSPHOROTRITHIOATE (DEF)
Authors: RAY D.E. 
Published: July 2012

Rats and mice given tributyl S,S,S,‐phosphorotrithioate (DEF) showed large dose‐related falls in body temperature which lasted from several hours to several days at environmental temperatures below thermoneutrality (30 to 31°C).
DEF produced only mild sedation and a remarkable degree of motor control was retained even when body temperatures fell below 30°C. At the dose producing maximal hypothermia only 2% of rats died within the first 24 h, although prolonged hypothermia was usually lethal.
Hypothermia was associated with a complete block of cold‐induced thermogenesis, with relatively little effect on basal metabolism at thermoneutrality.
Heat conservation mechanisms (peripheral vasoconstriction and piloerection) appeared to be unaffected by DEF and retained their usual temperature thresholds.
Adrenal catecholamine secretion in response to handling or acute cold exposure was normal in DEF‐treated rats but the fall in body temperature could be markedly reduced by large intraperitoneal injections of noradrenaline, although not atropine. The increase in oxygen consumption produced by injected catecholamines was also unaffected by DEF treatment.
It is concluded that the block of cold‐induced thermogenesis probably results from a lack of catecholamine release at the tissue level. That this is likely to be mediated at a peripheral site is suggested by the lack of effect of intracerebroventricular DEF.
BIOLOGICAL EFFECTS OF DEGRADATION PRODUCTS OF COLLAGEN BY BACTERIAL COLLAGENASE
Authors: BUCZKO WŁODZIMIERZ , DZIACZKOWSKI JAN , KOPEC MARIA , MONIUSZKO‐JAKONIUK JANINA , SOPATA IRENA , WISNIEWSKI KONSTANTY , WIZE JANINA , WOJTECKA‐ŁUKASIK ELŻBIETA 
Published: July 2012

Collagen degradation products (CDP) resulting from bacterial collagenase digestion were fractionated by gel filtration and their biological activities in rats were estimated.
CDP induced the following kinin‐like effects: increase in permeability of skin blood vessels, contraction of the isolated intestine of the rat, depression of locomotor activity and of motor coordination.
The most active CDP fraction was CDP III containing peptides of mol. wt. < 1000 D with a high percentage of hydroxyproline.
As compared with bradykinin, CDP III was less active in the skin permeability test and was 15,000 to 20,000 fold less effective in induction of isolated intestine contraction.
Depression of the CNS induced by 30 μg of CDP III administered into the brain ventricle was similar to that observed after 4 μg of bradykinin given by the same route.
CDP III prolonged the duration of sleep evoked by thiopentone and enhanced the threshold of convulsion induced by pentazol.
The activity of CDP in comparison to other low molecular weight peptides is discussed.
EFFECTS OF HARMINE ON TRANSMEMBRANE POTENTIALS OF GUINEA‐PIG ATRIAL MUSCLE
Authors: CARPENTIER ROBERT G. 
Published: July 2012

The effects of harmine 8.3 × 10−5 m on membrane potentials of guinea‐pig atrial muscle were analyzed and compared with those of harmaline. Transmembrane potentials of contractile fibres were measured during exposure to the drug at 30°C.
In preparations superfused with 5.4 mmol K+‐Tyrode, harmine produced a progressive reduction in the amplitude of the action potential (AP), in the absence of any change in resting potential (RP) and a prolongation of the duration of the action potential (APD).
Harmaline produced an enhancement of AP; RP was not affected and APD was prolonged.
The amplitude of slow responses elicited by noradrenaline in 16.2 mmol K+‐Tyrode was enhanced by harmine.
It is proposed that dehydrogenation of harmaline to harmine reverses the initial stimulatory action of harmaline on AP because the depressant action on the fast component of the upstroke prevails over the stimulatory effect on the slow component.
HISTAMINE WEAL FORMATION AND ABSORPTION IN MAN
Authors: COOK JOHN , SHUSTER SAM 
Published: July 2012

The weal and flare response to intradermal histamine was measured over a range of doses in forearm skin of man.
The use of calipers to measure weal thickness was validated by measurement of observer and method errors. Repeated measurements at intervals of 5 min or more compressed the weals by 6% per reading.
Flare response reached a maximum at 5 min compared with 20 min for weal thickness and the sensitivity of the flare response was greater than the weal response at lower doses of histamine.
Sensitivity, λ was comparable for the measurement of flare, weal diameter and thickness or volume. The advantage of weal thickness was in the measurement of weal formation and resorption.
The time course of histamine weal formation and disappearance was measured and found to have a T1/2 of 5.4 min and 87 min, respectively.
The T1/2 of disappearance of comparable 0.9% w/v NaCl solution and serum weals were 18 and 28 min respectively.
It is suggested that persistence of histamine weals is due to a vasoactive agent other than histamine.
RATE, FORCE AND CYCLIC ADENOSINE 3′, 5′‐MONOPHOSPHATE RESPONSES TO (—)‐ADRENALINE IN NEONATAL RAT HEART TISSUE
Authors: AU T.L.S. , COLLINS G.A. , WALKER M.J.A. 
Published: July 2012

(–)‐Adrenaline sensitivity in 1 to 20 day‐old rat heart tissue was investigated as rate, force and cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) production responses together with sensitivity to (±)‐propranolol blockade.
Resting performances were measured and responsiveness to (–)‐adrenaline then determined as ED50 values and maximal responses together with sensitivity to propranolol (pA2 values).
Resting force, corrected for sample size, did not change with age, whereas resting atrial rate doubled between 1 and 20 days.
ED50 concentrations in atria were constant with age, but decreased in ventricles. Cocaine (10−5 m) and other drugs did not consistently affect ED50 values.
Maximal responses were not age‐dependent in right atria, but increased in left atria. In 2 to 5 day‐old hearts there was no inotropic response to adrenaline and the very small maximal response in ventricles rose 5 to 7 fold by 20 days.
Propranolol sensitivity increased slightly (2 to 4 times) with age in all tissue from a pA2 value of 7.5 at 2 days to 8.2 at 20 days.
Control cyclic AMP was higher in 2 day than in 20 day‐old tissue and in atria than ventricular strips or hearts. In 2 and 20 day‐old atria, hearts and ventricles, force increases with different adrenaline concentrations correlated linearly with the log of the increase in cyclic AMP. Such a correlation was not seen in 2 day hearts and ventricles for cyclic AMP rose without corresponding force increases.
Results suggest slight maturational changes in atrial β‐receptors. In 1 to 5 day‐old ventricles, normal ED50 concentrations and good cyclic AMP response in the presence of a much reduced force response may indicate receptor‐response transduction inefficiency, assuming a β1‐receptor occupation and cyclic AMP production response mechanism for inotropism with adrenaline.
EVALUATION OF THE ROLE OF HISTAMINE H1AND H2‐RECEPTORS IN CUTANEOUS INFLAMMATION IN THE GUINEA‐PIG PRODUCED BY HISTAMINE AND MAST CELL DEGRANULATION
Authors: OWEN D.A.A. , POY ELISABETH , WOODWARD D.F. , DANIEL D. 
Published: July 2012

The role of histamine H1and H2‐receptors in mediating the cutaneous inflammatory response produced by exogenous histamine and the release of endogenous histamine from mast cells has been investigated by a method which permits simultaneous, quantitative measurement of vasodilatation, vascular permeability and oedema formation.Histamine and the selective H1‐receptor agonist, 2‐(2‐aminoethyl) pyridine, both produced vasodilatation, increased vascular permeability and oedema formation whereas the selective H2‐receptor agonist, dimaprit, produced only vasodilatation.Mepyramine and cimetidine both reduced the vasodilatation response to histamine, the combination of antagonists being superior to either antagonist alone. Mepyramine (but not cimetidine) virtually abolished extravascular albumin accumulation and oedema formation.Mepyramine and cimetidine both reduced the vasodilatation response produced by active cutaneous anaphylaxis and compound 48/80. However, mepyramine was less effective in reducing the vascular permeability response to mast cell degranulation than to histamine.In conclusion, the vasodilator response to histamine is mediated by both H1‐ and H2‐receptors; the permeability response to histamine is mediated solely by H1‐receptors. A combination of H1‐ and H2‐receptor antagonists appears to be more effective than either antagonist alone in reducing cutaneous inflammatory reactions involving histamine.
POTENTIATION OF THE CONTRACTILE RESPONSE TO ACETYLCHOLINE IN AORTIC STRIPS BY LOW CONCENTRATIONS OF VASCULAR CONTRACTILE AGONISTS
Authors: ASANO MASAHISA , HIDAKA HIROYOSHI 
Published: July 2012

The potentiating effect of a low concentration of various vascular contractile agonists on the response of rabbit aortic strips to acetylcholine was examined.
A marked parallel displacement to the left (potentiation; not additive effect) of the dose‐response curve for acetylcholine was observed when 5‐hydroxytryptamine (5‐HT), noradrenaline, histamine, angiotensin II or KCl were added at a concentration that caused only slight contraction (0.2 to 0.3 g) in the strips. This leftward displacement (potentiation) of the dose‐response curve by these agonists was reversed to the control response curve by the respective blocking agents for each agonist, although the blocking agents themselves did not shift the acetylcholine dose‐response curve to the right. Atropine produced a rightward displacement of the dose‐response curve for acetylcholine.
The addition of an extremely low concentration of 5‐HT or KC1 which did not cause contraction, also produced a potentiation.
The order of potency of the agonists in potentiating the acetylcholine‐induced contraction was KCl > 5‐HT ≥ histamine ≥ angiotensin II > noradrenaline.
The contractile response of aortic strips to carbamylcholine was also potentiated by these agonists.
The results suggest that the potentiation by these agonists was not mediated through muscarinic receptors but through the respective receptors for each agonist.
INHIBITION OF HISTAMINE RELEASE FROM HUMAN LUNG in vitro BY ANTIHISTAMINES AND RELATED DRUGS
Authors: CHURCH MARTIN K. , GRADIDGE CAROLYN F. 
Published: July 2012

A series of cationic, lipophilic histamine H1‐receptor antagonists, neuroleptics, antidepressants and monoamine oxidase inhibitors were tested for their effects on anti‐IgE‐induced histamine release from human lung fragments in vitro.
They had a biphasic effect: at low concentrations a dose‐related inhibition of histamine release was observed whereas, at higher concentrations, the drugs liberated histamine even in the absence of antigen.
Mepyramine, a much less lipophilic drug than the others tested, was only weakly active on mast cells at pharmacological concentrations.
The potency of the drugs as release inhibitors was not related quantitatively to their histamine liberating potency.
There was no correlation between activity on mast cells and histamine H1‐receptor antagonism.
Mast cell stabilization may play a part in the activity of these drugs as Antiallergic agents.
MECHANISM BY WHICH CYPROHEPTADINE INHIBITS INSULIN SECRETION
Authors: DONATSCH P. , LOWE D.A. , RICHARDSON B.P. , TAYLOR PAMELA 
Published: July 2012

Isolated islets of Langerhans from the rat have been used in studies designed to elucidate the mechanism by which cyproheptadine inhibits insulin secretion.
d‐Glucose and tolbutamide, both of which require extracellular Ca2+ to produce insulin release, failed to evoke a secretory response from islets pretreated with cyproheptadine. Conversely veratridine, the calcium ionophore A23187 and theophylline, all of which are capable of mobilizing sufficient intracellular Ca2+ to evoke insulin secretion in the absence of extracellular Ca2+, produced similar responses from cyproheptadine pretreated and control islets.
Cyproheptadine completely inhibited Ca2+ uptake induced by d‐glucose and high K+o, two agents which depolarize the islet β‐cell membrane, whilst Ca2+ uptake elicited by removal of extracellular Na+ (i.e. Na+‐Ca2+ counter transport) was only slightly reduced.
A significant increase in Na+ uptake produced by veratridine was sensitive to tetrodoxin but only partially reduced by cyproheptadine.
These results suggest that cyproheptadine inhibits depolarization‐dependent calcium entry into pancreatic β‐cells.
THE INTEGRITY OF THE SOCIAL HIERARCHY IN MICE FOLLOWING ADMINISTRATION OF PSYCHOTROPIC DRUGS
Authors: POSHIVALOV VLADIMIR P. 
Published: July 2012

Mice in small groups develop a despotic type of social hierarchy, a feature of which is to resist alteration through the medium of psychotropic drugs. This makes a rapid pharmacologically induced change in the social hierarchy impossible.
Patrolling the territory and a certain level of social interaction are both critical factors in maintaining the phenomenon of inertia in the social hierarchy. Psychotropic drugs (diazepam, droperidol and mescaline) altered both these factors to a varying degree and also displayed a differing ability to maintain the inertia of the social hierarchy.
A drug‐induced alteration in the level of aggression in a subordinate mouse in a group of three does not cause an alteration in its social position.
Chronic administration of diazepam, droperidol or mescaline, all of which alter the level of aggression in different ways, can result in an inversion of the social hierarchy where a competitive rival is present in the group of mice. The rate of inversion of the social hierarachy depends on the type of pre‐existing social hierarchy.
It is suggested that the ability of psychotropic drugs to maintain the inertia of the hierarchy be used as an index of their effect upon certain types of species‐specific behaviour; in particular aggression.
THE EFFECTS OF THE CALCIUM IONOPHORE, A23187, ON THE AXOPLASMIC TRANSPORT OF DOPAMINE β‐HYDROXYLASE
Authors: ESQUERRO E. , GARCIA A.G. , SANCHEZ‐GARCIA P. 
Published: July 2012

The effects of the ionophore, A23187, on the intra‐axonal transport of dopamine β‐hydroxylase (DBH) were investigated in the cat hypogastric nerve‐inferior mesenteric ganglion preparation by monitoring, in vitro, the enzyme accumulation above a ligature, 2 to 2.5 cm distal to the ganglion.
DBH accumulation in the proximal segment immediately above the ligature (P1) increased linearly up to 6 h, during incubation in normal Krebs solution at 37°C. The ionophore, A23187, interfered with the enzyme accumulation, but did not modify the previously accumulated DBH activity present in P1.
The blocking effects of A23187 on DBH transport were greatly impaired in the absence of extracellular calcium ions; an excess of calcium in the bathing solution (7.5 mM) itself blocked the enzyme transport by 50%.
A23187 did not significantly modify the levels of adenosine triphosphate (ATP) in the segments P1 and P2 of the nerve proximal to the ligature.
Nerves incubated in an A23187‐containing medium showed many mitochondria of normal shape and fine structure; however, typical microtubules or filaments were not seen in these preparations.
The results suggest that the ionophore A23187, by considerably raising the axoplasmic ionized calcium levels, interferes with the assembling of microtubules. In this manner, the ionophore would inhibit the transport of adrenergic vesicles and therefore of DBH along the axon. The results also provide additional evidence in favour of the view that for the transport system to work adequately, it is necessary to maintain the intra‐axoplasmic ionized calcium concentration between certain critical levels.
PHARMACOLOGICAL DIFFERENTIATION OF PRESYNAPTIC INHIBITORY α‐ADRENOCEPTORS AND OPIATE RECEPTORS IN THE CAT NICTITATING MEMBRANE
Authors: DUBOCOVICH MARGARITA L. , LANGER S.Z. 
Published: July 2012

The action of morphine, naturally occurring and synthetic opiate peptides on [3H]‐noradrenaline release induced by nerve stimulation was studied in the isolated nerve muscle preparation of the cat nictitating membrane under experimental conditions in which the α‐presynaptic receptors were blocked by phentolamine 1 μm.
Morphine and the naturally occurring peptides: [Met5]‐enkephalin, [Leu5]‐enkephalin and β‐endorphin reduced 3H‐transmitter overflow and responses to nerve stimulation from the cat nictitating membrane, effects which were completely antagonized by naloxone 0.3 μm. The relative order of potency for the inhibition of the stimulation‐induced 3H‐transmitter overflow at the level of the IC50 (μm) was as follows: [Met5]‐enkephalin (0.020 μm) ≥ [Leu5]‐enkephalin (0.036 μm) > morphine (0.3 μm) > β‐endorphin (1 μm).
The synthetic opiate pentapeptides: BW 180 C (Tyr‐d‐Ala‐Gly‐Phe‐d‐Leu), and BW834 C (Tyr‐d‐Ala‐Gly‐pC1Phe‐dLeu), which are resistant to enzymatic degradation were more potent than the enkephalins in reducing the stimulation‐evoked transmitter overflow from the cat nictitating membrane. On the other hand, the tetrapeptide BW832 C, which lacks the d‐leucine terminal of BW180 C was less potent than the enkephalins in inhibiting neurotransmission.
In the presence of phenoxybenzamine 1 μm, 3H‐transmitter overflow was increased 8 fold and the inhibition of neurotransmission by methionine‐enkephalin was not affected. Exposure to phenoxybenzamine 10 μm increased [3H]‐noradrenaline overflow 15 fold and antagonized the effects of methionine enkephalin on transmitter release.
In the cat nictitating membrane the inhibitory presynaptic opiate receptors are different from the presynaptic α‐autoreceptors which regulate the release of noradrenaline elicited by nerve depolarization through a negative feed‐back mechanism.
THE EFFECT OF PRAZOSIN ON THE GUINEA‐PIG ILEUM
Authors: FAGBEMI S.O. , SALAKO L.A. 
Published: July 2012

The α‐adrenoceptor blocking activity of prazosin was compared with that of phentolamine, yohimbine and phenoxybenzamine in the guinea‐pig isolated ileum.
Phentolamine (2.56 × 10−8 to 2.56 × 10−6 m) and yohimbine (5.12 × 10−8 to 5.12 × 10−6 m) antagonized the sympathetic inhibition of twitches induced by transmural stimulation, whereas prazosin (5.28 × 10−8 to 5.28 × 10−6 m) and phenoxybenzamine (4.2 × 10−9 to 4.2 × 10−7 m) had no effect.
Phentolamine, yohimbine, prazosin and phenoxybenzamine antagonized the relaxant response of the ileum to periarterial nerve stimulation and to exogenous noradrenaline in the absence of transmural stimulation.
The pA2 value for phentolamine against noradrenaline in the transmurally‐stimulated gut (presynaptic α‐adrenoceptor site; 8.17 ± 0.04) was significantly different from that in the non‐stimulated gut (postsynaptic α‐adrenoceptor site; 6.88 ± 0.12).
Phentolamine and prazosin probably block noradrenaline responses at the same α‐adrenoceptor site on the postsynaptic membrane.
EFFECTS OF RMI 12330A, A NEW INHIBITOR OF ADENYLATE CYCLASE ON MYOCARDIAL FUNCTION AND SUBCELLULAR ACTIVITY
Authors: GRUPP G. , GRUPP I.L. , JOHNSON C.L. , MATLIB M.A. , ROUSLIN W. , SCHWARTZ A. , WALLICK E.T. , WANG T. , WISLER P. 
Published: July 2012

RMI 12330A, a lactam‐imine, at concentrations of 10−4 m and higher, inhibited basal as well as isoprenaline and NaF‐stimulated adenylate cyclase activity of guinea‐pig heart homogenates. However, RMI 12330A was a more potent inhibitor of histamine‐stimulated adenylate cyclase (IC50 of 1.5 × 10−5 m).
In the isolated work‐performing heart of the guinea‐pig, RMI 12330A (IC50 of 1.1 × 10−6 m) depressed all cardiac functions: pressures developed, dP/dt, contractile force, dF/dt, work performance and stroke work. Left atrial pressure rose and the positive inotropic response to increasing heart rate (staircase) became negative. Histamine, isoprenaline and ouabain no longer caused positive inotropic effects.
Increasing the perfusate calcium concentration from 2.5 mm to 4.5 and 6.5 mm completely restored cardiac function after its depression by RMI 12330A.
RMI 12330A uncoupled mitochondrial oxidative phosphorylation; the classical uncoupler, dinitrophenol, had the same effects on cardiac dynamics as RMI 12330A.
RMI in high doses inhibited hydrolytic activity of Na+, K+‐ATPase of crude and purified heart preparations (IC50 of 1.7 × 10−4 m) and inhibited ouabain binding to the same enzymes (IC50 of 1.5 × 10−4 m).
A lactam‐imine analogue of RMI 12330A that had no effect on adenylate cyclase, was also without effect on any of the systems examined.