bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACTIVITY OF CANNABIS IN RELATION TO ITS Δ‘‐trans‐TETRAHYDROCANNABINOL CONTENT
Authors: FAIRBAIRN J.W. , PICKENS JOAN T. 
Published: July 2012

Conditions have been worked out for a reliable estimation of the cataleptic activity of Δ′‐trans‐tetrahydrocannabinol (THC) after oral administration to mice, using the ring test over a period of 6 h.
By this method, the activity of cannabis herb and 5 crude fractions were measured against THC; at the same time the THC contents were determined chemically.
The B/C ratio (biological activity divided by chemical assay) was calculated for each. With cannabis herb the value was 3.3 and with extracts prepared with ethanol or 70% ethanol the values ranged from 3.2 to 7.1, indicating that in all samples the activity was much higher than would be expected from their THC content.
The cannabinoids were completely extracted from a sample of herb using petroleum spirit and the marc examined for a possible synergist. Surprisingly, it contained a powerful inhibitor of the action of THC, which could be restored by intraperitoneal prostaglandin E2 (3 μg/kg). Some crude fractions had inhibitory activities about 10 times that of aspirin.
In contrast, the petroleum spirit extract (referred to in 4) had a surprisingly high B/C ratio of 23, indicating that a powerful synergist of THC activity is present.
The net effect of the herb and ethanol extracts is probably due to a balance of synergist and inhibitor.
THE EFFECT OF TAURINE ON HIGH POTASSIUM‐ AND NORADRENALINE‐INDUCED CONTRACTION IN RABBIT EAR ARTERY
Authors: FRANCONI FLAVIA , GIOTTI ALBERTO , MANZINI STEFANO , MARTINI FLAVIO , STENDARDI ISABELLA , ZILLETTI LUCILLA 
Published: July 2012

Intraluminal administration of taurine (40 mm) did not affect the contractile tone of rabbit isolated ear artery.Taurine (10–80 mm) exerted a powerful concentration‐dependent, vasodilator action in arteries contracted with high potassium medium.In the same experimental conditions, the taurine analogues β‐alanine and homotaurine, had no effect.Taurine (40–80 mm) did not affect in a significant manner the tonic component of the noradrenaline (5 × 10−6m)‐induced contraction.When noradrenaline (5 × 10−6m) was followed by the administration of high potassium medium a further increase in intraluminal pressure was observed. Under these conditions taurine (40 mm) reversed specifically the component due to the high potassium medium.
Spasmolytic effect of cadmium and cadmium uptake in aorta
Authors: Nasu Tetsuyuki 
Published: July 2012

The relationship between inhibition of tension by Cd2+ in aorta and the kinetics of cadmium uptake and efflux was studied. Cd2+ (0.01–0.5 mm) inhibited the contraction of aorta to high‐K+ (30 mm) in a dose‐dependent manner.
The high‐K+‐induced tension completely returned to control values after 60 min washing with a solution containing 5 mm disodium edetate (EDTA) or 5 mm cysteine, following a treatment with 0.5 mm Cd2+ for 30 min; after washing with normal medium only 15% of the control response returned.
Cadmium uptake increased with an increase of the Cd2+ concentration (0.01–0.5 mm).
Aortae preincubated with 0.5 mm Cd2+ for 60 min were washed subsequently with a medium containing 5 mm EDTA or 5 mm cysteine. About 5% of the original tissue cadmium was retained after washing with EDTA or cysteine.
It is suggested that Cd2+ binds chiefly to the surface membrane of aorta. It seems possible that the quantity bound is correlated with the degree of inhibition of tension.
Blood pressure changes in spontaneously hypertensive rats correlate with aortic prostacyclin formation
Authors: Fahr A. , Förster W. , Taube Ch. 
Published: July 2012

The relationship between the blood pressure fall, induced by antihypertensive drugs or bleeding, and the formation of prostacyclin (PGI2)‐like activity in the thoracic aorta of spontaneously hypertensive rats has been investigated. Inhibition of ADP‐induced platelet aggregation was used to assess PGI2‐like activity.
The decreases in blood pressure produced by clonidine, dihydralazine and prazosin were associated with increases of PGI2‐like activity of 50–80%. The increase in PGI2‐like activity correlated well with the blood pressure decrease, independently of the mechanism of the fall in blood pressure.
The role of histamine receptors in the release of renin
Authors: Gerber J.G. , Nies A.S. 
Published: July 2012

The effect of intrarenal histamine, dimaprit (H2‐agonist) and 2‐(2‐pyridyl) ethylamine (H1‐agonist) on renin release was examined in anaesthetized dogs.
In dogs with intact kidneys, histamine and dimaprit administration resulted in renal vasodilatation, a two fold increase in urinary sodium excretion, and no change in renal renin release. 2(2‐Pyridyl) ethylamine administration resulted in renal vasodilatation, a 25% decrease in urinary sodium excretion and a significant increase in renin release.
In dogs with non‐filtering kidneys, dimaprit administration resulted in renal vasodilatation and a significant increase in renin release, while 2(2‐pyridyl) ethylamine administration resulted in renal vasodilatation but no change in renin release.
Our data suggest that histamine is a potential participant in the release of renin through stimulation of H2‐receptors, but it is a weak agonist.
In addition, the direct effect of histamine analogues on renin release is modulated by their effects on electrolyte excretion probably by influencing the renal chemoreceptor release of renin mediated by the macula densa.
Classification of β‐adrenoceptors in isolated bronchus of the pig
Authors: Goldie Roy G. , Paterson James W. , Wale Janet L. 
Published: July 2012

(±)‐Isoprenaline (Iso), (−)‐adrenaline (Ad), (−)‐noradrenaline (NA), the β2‐selective adrenoceptor agonist (±)‐fenoterol (Fen) and the β1‐selective adrenoceptor agonist (±)‐RO363 caused concentration‐dependent relaxation of preparations of pig bronchus pre‐contracted with carbachol 40 ng/ml (0.22 μM). Iso, Ad, NA and Fen caused complete relaxation of carbachol‐induced tone, but RO363 caused relaxation equivalent to only 59% of the maximal response to Iso.
When relaxation responses to these amines were plotted as a % of their maximal effects, comparison of EC50 values showed that the order of potency was RO363 > Iso > NA > Fen > Ad (14.4:4.6:1:0.4:0.3).
pA2 values determined for the β‐adrenoceptor antagonists propranolol (non‐selective) and atenolol (β1‐selective), or the partial agonist salbutamol (β2‐selective) using Iso as agonist were 8.3, 7.3 and 4.4 respectively. The pA2 value for atenolol using RO363 as the agonist was 7.6.
These results indicate that porcine bronchus contains a homogeneous population of β1‐adrenoceptors.
H1‐histamine receptors may mediate the contractile response of guinea‐pig ileum to ‘histamine‐free’ splenic extracts
Authors: Ainz L.F. , Casis E. , de Gandarias J.M. , Gil‐Rodrigo C.E. , de Gandarias J.J. Goiriena 
Published: July 2012

A water‐soluble splenic factor, which produces a contractile response of the guinea‐pig ileum, that is resistant to cholinoceptor and adrenoceptor antagonists is described.
The ileal contractions elicited by the splenic extract showed some significant differences from those elicited by 5‐hydroxytryptamine. The responses to splenic extract were not affected by the D‐tryptamine‐receptor antagonist, methysergide.
The effect of the splenic extract on the guinea‐pig ileum was similar to that of histamine. The H1‐histamine antagonists, (+)‐chloropheniramine and diphenhydramine, caused a parallel shift to the right of the splenic extract dose‐response curve without suppression of the maximum response. A pA2 value of 8.97 ± 0.03 for (+)‐chlorpheniramine and 7.55 ± 0.1 for diphenhydramine was calculated.
Significant histamine levels, as determined by fluorometric methods, could not be detected in the splenic extract. Likewise, the splenic factor did not release histamine from the intestinal preparation.
These results support the view that: (i) the splenic factor acts through H1‐histamine receptors; (ii) it is not histamine; (iii) it does not have any histamine releasing effect on the ileal smooth muscle.
Inhibition of lymphocyte activation by gold sodium thiomalate
Authors: Hopkins Stephen J. , Jayson Malcolm I.V. , Van der Zeil Peter 
Published: July 2012

Activation of lymphoid cells by both T and B cell mitogens was inhibited by gold sodium thiomalate (GST).
The action of GST did not appear to be exerted at early stages of lymphocyte activation.
Inhibition by GST was sustained throughout 4 days of culture.
The inhibitory effect of GST was reduced at low serum concentrations.
Sodium thiomalate and sodium chloroaurate were also able to inhibit lymphocyte activation.
Antagonism of tetrodotoxin‐ and procaine‐induced axonal blockade by adenine nucleotides in the frog sciatic nerve
Authors: Ribeiro J. A. , Sebastião A.M. 
Published: July 2012

The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine on compound action potentials were investigated in de‐sheathed frog‐sciatic nerve preparations.
ATP and ADP but not adenosine antagonized the inhibitory action of tetrodotoxin (TTX) on nerve conduction. AMP had little or no antagonistic effect on TTX‐induced axonal block. ATP was more effective than ADP. The effects of the nucleotides were related to the degree of the TTX‐induced inhibition and were more evident where the blockade was more intense.
ATP and ADP but not adenosine antagonized the procaine‐induced axonal blockade which, in some experiments, was completely reversed by these nucleotides. ATP and ADP were of similar potency.
The axonal blockade induced by pentobarbitone was not antagonized by ATP, ADP, AMP or adenosine.
The possibility that ATP stimulates a TTX‐sensitive sodium channel is discussed.
Relationship between structure of phenothiazine analogues and their activity on platelet calcium fluxes
Authors: Enouf J. , Lévy‐Toledano S. 
Published: July 2012

Phenothiazine analogues have been tested for their effect on calcium uptake into platelet membrane vesicles and on ionophore‐induced platelet activation, both phenomena being Ca2+‐dependent.
Both calcium uptake into membrane vesicles and ionophore‐induced platelet activation were inhibited by the drugs.
Evidence for two inhibitors as potent as chlorpromazine and trifluoperazine was found.
These drugs are apparently competitive inhibitors of calcium uptake.
A structure‐activity relationship has been established.
The data suggest that the phenothiazines are able to inhibit calmodulin‐insensitive calcium uptake of platelet membrane vesicles and that therefore they cannot be assumed to be selective inhibitors of calmodulin interactions under all circumstances.
The effects of ryanodine, EGTA and low‐sodium on action potentials in rat and guinea‐pig ventricular myocytes: evidence for two inward currents during the plateau
Authors: Mitchell Mary R. , Powell T. , Terrar D.A. , Twist V.W. 
Published: July 2012

Action potentials were recorded from single cells isolated from rat and guinea‐pig ventricular muscle. In rat cells the repolarization showed two distinct phases, referred to as the early and late phases. In guinea‐pig cells there was a maintained plateau.
Reducing external sodium by replacement with lithium or choline suppressed the late phase of the action potential in rat cells, and shortened the plateau of the action potential in guinea‐pig cells.
Intracellular EGTA abolished contraction while suppressing the late phase of the action potential in rat cells, and shortening the plateau in guinea‐pig cells.
Ryanodine (1 μm), which is thought to inhibit the release of calcium from internal stores, suppressed contraction and the late phase of the action potential in rat cells. In guinea‐pig cells, there was no substantial effect of ryanodine (1 μm) on either contraction or the time course of the action potential.
The late phase of the action potential in rat cells was suppressed by increasing the external potassium concentration to 12 mm, and enhanced by reducing external potassium to 1.2 mm
It is concluded that an inward current activated by internal calcium contributes to the late phase of the action potential in rat cells, and to the plateau in guinea‐pig cells. Two possibilities are a current arising from electrogenic sodium‐calcium exchange, and a current through ion channels activated by calcium. The effects of reducing external sodium would be consistent with either mechanism. The contribution of such an inward current would be expected to be modified by outward currents through a rectifying potassium conductance which varies with external potassium concentration. In the rat, but not the guinea‐pig, the rise in internal calcium which activates the inward current seems to be largely dependent on ryanodine‐sensitive release of calcium from internal stores.
Dual population of GABAA and GABAB receptors in rat pars intermedia demonstrated by release of αMSH caused by barium ions
Authors: Demeneix Barbara A. , Desaulles Eric , Feltz Paul , Loeffler Jean‐Philippe 
Published: July 2012

We have studied the effects of selective GABAA and GABAB agonists on α‐melanophore stimulating hormone (αMSH) release from intact rat neurointermediate lobes (NIL) in vitro. Agonist effects were tested against either basal αMSH output or BaCl2 (5 mM)‐evoked release.
GABA (50 μM) produced a biphasic effect on basal release, with an enhancement followed by inhibition of release. The enhancement but not the inhibition was blocked by bicuculline methiodide (100 μM).
Baclofen (10 μM), a specific GABAB agonist, reduced the basal and Ba2+‐evoked hormonal release in a stereospecific manner. (−)−Baclofen (5 μM) was active whereas the (+)‐isomer was inactive at the same concentration.
Isoguvacine (50 μM) a specific GABAA agonist, potentiated the Ba2+‐evoked release of αMSH. GABA (50 μM) mimicked this effect, and its action was antagonized by bicuculline methiodide (200 μM).
The results suggest that both GABAA and GABAB receptors are present on the endocrine cells of the intermediate lobe.
Release of dynorphin, somatostatin and substance P from the vascularly perfused small intestine of the guinea‐pig during peristalsis
Authors: Donnerer Josef , Holzer Peter , Lembeck Fred 
Published: July 2012

The release of dynorphin‐(1–17), somatostatin and substance P into the venous effluate of the isolated and vascularly perfused guinea‐pig small intestine was measured during rest and peristaltic activity. The peptides were determined by specific radioimmunoassays.
Increasing the intraluminal pressure by 5 mbar increased the release of dynorphin‐(1–17), somatostatin and substance P. A substantial increase in the release of substance P was only seen in the presence of naloxone (1.5 μM) indicating an inhibitory influence of opioid peptide‐containing neurones on the release of substance P. The pressure‐induced release of substance P and dynorphin‐(1–17) was completely prevented by tetrodotoxin (1.3 μM), which suggests a neural origin of these two peptides. The pressure‐induced release of somatostatin was only partially inhibited by tetrodotoxin (1.3 μM) suggesting that somatostatin may also be released from non‐neuronal sources, i.e. endocrine mucosal cells.
Dimethylphenylpiperazinium (32 μM) increased the release of somatostatin and substance P and this effect was inhibited by tetrodotoxin (1.3 μM). Cholecystokinin‐octapeptide (38 μM) induced a large increase in the release of somatostatin but only a minute increase in the release of substance P; these effects of cholecystokinin‐octapeptide were not blocked by tetrodotoxin (1.3 μM).
Noradrenaline (59 μM) inhibited the pressure‐induced release of substance P but not that induced by dimethylphenylpiperazinium (32 μM). Neither the pressure‐induced nor the dimethylphenylpiperazinium‐evoked release of somatostatin was significantly diminished by noradrenaline.
These results indicate that dynorphin‐(1–17), somatostatin and substance P may be transmitters involved in the coordination of the peristaltic reflex. Part of the inhibitory effects of opioid peptides and noradrenaline on intestinal motility may be brought about by inhibition of the release of substance P.
Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling
Authors: Little Hilary J. , Nutt David J. , Taylor Stuart C. 
Published: July 2012

The effects of the acute and chronic administration of the β‐carboline benzodiazepine receptor ligand, FG 7142 were studied in mice.
On acute administration FG7142 (at doses between 10 and 40 mgkg−1) lowered seizure thresholds to infused pentylenetetrazol (PTZ) but showed an unusual dose‐response curve in that higher doses had less effect. The duration of action was considerably longer than that of other β‐carbolines, such as ethyl‐β‐carboline‐3‐carboxylate (βCCE).
During repeated administration, doses of FG7142 which were initially proconvulsant subsequently produced generalized seizures on average in 60% of animals after 12 once daily treatments. This seemed to be a form of chemical kindling.
The effects of different drug administration regimes were studied. Once daily dosage was shown to be the optimum for kindling production, and was therefore used for subsequent experiments.
Kindling lasted for at least one month after 12 single once daily doses of 40 mgkg−1 (FG 7142).
The administration of the benzodiazepine antagonist Ro 15–1788 concurrent with FG7142 prevented kindling. When Ro 15–1788 was given to kindled animals along with a challenge dose of FG7142, it prevented the expression of kindled seizures. These data show that kindling is mediated via the benzodiazepine receptor.
Effects of bronchoconstrictors and bronchodilators on a novel human small airway preparation
Authors: Finney M.J.B. , Karlsson J.‐A. , Persson C.G.A. 
Published: July 2012

Human lung bronchiolar segments (about 2 mm long and with a diameter of 0.6‐1.5 mm) were dissected and circular muscle tension recorded. Airways were identified by histology and in some preparations by relaxant responses to noradrenaline (0.1–10 μM).
Adenosine (1–100 μM) produced only very weak contractions, whereas carbachol (EC50 = 0.40 μM), histamine (EC50 = 0.63 μM), prostaglandin D2 (EC50 = 0.50 μM), substance P (EC50 = 4.6 μM) and ATP (1–100 μM) produced much greater ones.
The contractions generally developed rapidly and were stable. The mean maximum increase in tension achieved with the most efficient constrictor, carbachol, was 0.5 g. ATP was the least efficient producing only about 40% of carbachol's maximum.
Terbutaline, theophylline and enprofylline relaxed carbachol (2.0 μM = EC70)‐contracted preparations. Terbutaline (3–3000 nM) relaxed 4 out of 11 bronchioles. Theophylline (10–4000 μM) and enprofylline (1–400 μM) consistently relaxed the bronchiolar preparations including those exhibiting little responsiveness to the β2‐adrenoceptor agonist.
Since enprofylline (which does not block adenosine receptors) was a five times more potent relaxant than theophylline and since adenosine produced only weak contractions, antagonism of adenosine receptors is probably not involved in relaxation of the small airways.
It is suggested that the present data, which apparently differ from those obtained with lung parenchymal strips, are of relevance for human small airways responsiveness.
Effect of verapamil and diltiazem on calcium‐dependent electrical activity in cardiac Purkinje fibres
Authors: Amerini Sandra , Giotti Alberto , Mugelli Alessandro 
Published: July 2012

The effects of verapamil and diltiazem on normal action potentials, abnormal automaticity at depolarized membrane potential and oscillatory afterpotentials were compared in sheep cardiac Purkinje fibres.
Concentrations of verapamil and diltiazem exerting the same action on abnormal automaticity due to slow action potentials, caused different effects on action potential characteristics and on oscillatory afterpotentials.
Diltiazem significantly shortened action potential duration whereas verapamil slightly lengthened it (NS).
Diltiazem appeared to be more effective than verapamil in preventing the development of oscillatory afterpotentials induced by barium or by strophanthidin.
In 50% of barium‐treated preparations, verapamil caused the appearance of spontaneous activity due to enhanced normal diastolic depolarization, while diltiazem had no such effect.
The observed differences were explained in terms of the different effects of the two drugs on currents other than the slow inward current, since diltiazem was more potent than verapamil in depressing max.
A search for selective antagonists at M2 muscarinic receptors
Authors: Barlow R. B. , Shepherd M.K. 
Published: July 2012

Isolated preparations of guinea‐pig ileum and atria have been used to estimate the dose‐ratios produced by antagonists at muscarinic receptors. Experiments with 4‐diphenyl‐acetoxy‐N‐methylpiperidine (4DAMP) metho‐salts and with its isomer, 3DAMP methiodide, indicate that these are only slightly affected by the choice of physiological salt solution, the choice of agonist and the presence or absence of hexamethonium.
Methyl or chloro groups in the p‐position of the two benzene rings in 4DAMP metho‐salts markedly reduce affinity and selectivity.
When the two benzene rings are linked together, as in the fluorene‐9‐carboxylic ester, the affinity for the receptors in the atria is comparable with that of 4DAMP methobromide but that for the ileum is about half, so the selectivity is reduced. When the rings are linked as in the xanthene‐9‐carboxylic ester, the affinity for receptors in both tissues is greater than that of 4DAMP methobromide but there is less selectivity.
When two molecules of 4DAMP are linked together by a polymethylene chain of from 4 to 12 carbon atoms the effects on affinity for muscarinic receptors in the guinea‐pig ileum are different from those on affinity for muscarinic receptors in guinea‐pig atria. The pentamethylene compound is the most selective: compared with 4DAMP methobromide it has slightly less affinity for receptors in the ileum but much less affinity for receptors in the atria.
The effects of the compounds in antagonizing the actions of carbachol on atrial rate are not markedly different from their effects in antagonizing its actions on the force of the atrial contractions.