bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROLE OF CYCLIC ADENOSINE 3‘,5’‐MONOPHOSPHATE IN THE ISOPRENALINE‐INDUCED RELAXATION OF THE OESTROGEN DOMINATED RABBIT UTERUS
Authors: NESHEIM BRITT—INGJERD , OSNES J.‐B. , ØYE I. 
Published: July 2012

The role of cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) in the relaxation produced by isoprenaline in muscle strips from the oestrogen dominated rabbit uterus has been investigated.
Isoprenaline 2 × 10−8 M produced an inhibition of the mechanical activity but no increase in cyclic AMP. Isoprenaline 2 × 10−6 M produced both inhibition of mechanical activity and increase in cyclic AMP.
The increase in cyclic AMP, but not the inhibition of mechanical activity, was blocked by propranolol 3.4 × 10−6 M.
Dibutyryl‐cyclic AMP produced a relaxation which mimicked that produced by isoprenaline, in that the longitudinal strips were more sensitive than the circular ones.
It is concluded that cyclic AMP may be a mediator of the β‐adrenergic effect in the oestrogen dominated rabbit myometrium. However, it seems not to be an obligatory link between stimulation of β‐adrenoceptors and relaxation. Other mechanisms may also exist.
THE EFFECTS OF MORPHINE ON THE RELEASE OF NORADRENALINE FROM THE CAT ISOLATED NICTITATING MEMBRANE AND THE GUINEA‐PIG ILEUM MYENTERIC PLEXUS‐LONGITUDINAL MUSCLE PREPARATION
Authors: HENDERSON G. , HUGHES J. , KOSTERLITZ H.W. 
Published: July 2012

Electrical field stimulation of either the cat isolated nictitating membrane or the guinea‐pig ileum myenteric plexus‐longitudinal muscle preparation caused the release of noradrenaline into the bathing medium.
In the cat nictitating membrane, the output per pulse of noradrenaline was constant at frequencies of stimulation from 0.5 to 15 Hz. In the guinea‐pig myenteric plexus preparation the output per pulse of noradrenaline increased as the frequency of stimulation was increased from 2 to 16 Hz.
Phenoxybenzamine (29.3 μM) caused a marked increase in the noradrenaline output from both the cat nictitating membrane and guinea‐pig myenteric plexus preparations.
Morphine (0.13‐8 μM) inhibited the contractions of the cat nictitating membrane caused by electrical stimulation. This effect was greater at low (1 Hz) than at high (15 Hz) frequencies of stimulation. The site of action is at the nerve‐smooth muscle junction.
The action of narcotic analgesic drugs on the cat nictitating membrane showed stereospecificity. Naloxone (0.1 μM) reversed the inhibition caused by normorphine (3.2 μM).
Morphine (3 μM) reduced the noradrenaline output from the cat nictitating membrane stimulated at 1 Hz but not at 15 Hz. At 1 Hz, the inhibition of noradrenaline output by normorphine (5 μM) was reversed by naloxone (0.25 μM).
Morphine (1.5 μM) did not alter the noradrenaline output from the guinea‐pig myenteric plexus preparation stimulated at 2 or 16 Hz.
PROSTAGLANDINS IN PYOMETRIAL FLUID FROM THE COW, BITCH AND FERRET
Authors: HEAP R.B. , POYSER N.L. 
Published: July 2012

Pyometra is a disorder of the uterus usually associated with bacterial infection plus obstruction.
Large quantities of fluid often collect in the uterus during this condition.
Pyometrial fluid obtained from three species was found to contain prostaglandin F2α, usually in large quantities.
Prostaglandin E2 was present in smaller quantities in five of the six samples.
These findings are discussed in relation to the known occurrence of prostaglandins in inflammatory fluid, and to the problem of infertility.
THE EFFECTS OF TETRAPHENYLBORON ON SPONTANEOUS TRANSMITTER RELEASE AT THE FROG NEUROMUSCULAR JUNCTION
Authors: MARSHALL I.G. , PARSONS R.L. 
Published: July 2012

The effects of tetraphenylboron (TPB) on spontaneous transmitter release were studied in the frog sartorius muscle preparation.
TPB (0.001‐1 mM) produced a time‐dependent increase in miniature endplate potential (m.e.p.p.) activity that was not sustained. TPB (0.1 mM) produced similar effects on m.e.p.p. frequency in normal Ringer solutions, in the absence of Ca2+ or Cl− and in the presence of excess Ca2+ and of tetrodotoxin. The effect of TPB (0.01 mM) was reduced but not abolished in the absence of Ca2+.
As m.e.p.p. frequency fell from its peak level in TPB (0.04 mM) m.e.p.p. amplitude was reduced. The reduction of m.e.p.p. amplitude was not prevented by choline (30–300 μM).
When m.e.p.p. activity fell below the noise level in the presence of TPB (0.1 mM), lanthanum (0.5 mM) was ineffective in promoting measurable m.e.p.p. activity.
The effects of TPB were slowly reversible by washing.
The results indicate that TPB acts to reduce the nerve terminal stores of acetylcholine, probably by a combination of rapid release and concomitant inhibition of transmitter storage.
RENAL TUBULAR TRANSPORT OF PARACETAMOL AND ITS CONJUGATES IN THE DOG
Authors: DUGGIN G.G. , MUDGE G.H. 
Published: July 2012

The renal tubular transport of paracetamol and its conjugates was investigated with renal clearance and stop flow studies in the dog. Paracetamol is sparingly bound to plasma proteins and therefore undergoes glomerular filtration. It is reabsorbed in the renal tubules by simple diffusion.
The conjugates of paracetamol, the sulphate and the glucuronide, both undergo glomerular filtration being weakly protein bound. At low concentrations in plasma both compounds are secreted by an active transport process. At higher concentrations both compounds are reabsorbed. Clearances are not dependent on urinary pH or flow rate. It is concluded that reabsorption is not a passive process but that there is an active bidirectional transport of the conjugates.
Net tubular secretion of the sulphate, but not the glucuronide, conjugate was inhibited by the administration of probenecid.
DECAMETHONIUM IN THE PERFUSED AND IMMERSED RAT DIAPHRAGM
Authors: HUMPHREY P.P.A. 
Published: July 2012

The water content and mannitol space of rat diaphragms which were perfused through the inferior vena cava was increased compared with immersed diaphragms. The potassium content of both preparations, when expressed in terms of dry weight, was maintained at similar values to that found in vivo.
Despite the application of a constant concentration of decamethonium, a steady level of neuromuscular block was not obtained in either the perfused or immersed rat diaphragm. The immersed preparation differed from the perfused preparation in that recovery from paralysis occurred despite the continued presence of the drug.
The rate of uptake of labelled decamethonium (100 μM) at the end‐plate region was similar in the perfused and immersed diaphragm. The slopes of the regressions were 0.059 and 0.054 μ1 mg−1 min−1 (based on dry weight) respectively which were not significantly different. This implies that the rate of uptake of the drug at the end‐plate is slow and limited by the rate of entry into the fibre rather than by diffusion to the site of entry.
THE EFFECTS OF CYCLIC N‐2‐O‐DIBUTYRYL‐ADENOSINE 3′, 5′‐MONOPHOSPHATE, ADRENALINE AND AMINOPHYLLINE ON THE ISOMETRIC CONTRACTILITY OF THE ISOLATED HEMIDIAPHRAGM OF THE RAT
Authors: KENTERA D. , VARAGIĆ V.M. 
Published: July 2012

N‐2‐O‐dibutyryl adenosine 3′,5′‐monophosphate (db cyclic AMP), adrenaline and aminophylline produce a potentiation of the tension developed (Td) and the maximum rate of rise of tension (dT/dt max) in the rat isolated diaphragm during indirect electrical stimulation. Aminophylline and db cyclic AMP also produce the same effect during direct stimulation.
Propranolol produced a depression of the action of adrenaline on Td and dT/dt max during indirect stimulation of the diaphragm. On the other hand, the potentiating actions of db cyclic AMP and of aminophylline on Td and dT/dt max during indirect stimulation were unaffected by propranolol.
The results support the idea that cyclic AMP may be involved not only in regulating the processes associated with synthesis, mobilization and storage of transmitter in the motor nerve terminal, but also in modifying some metabolic processes which regulate the function of the contractile elements.
ON THE ABILITY OF PROSTAGLANDIN E1 AND ARACHIDONIC ACID TO MODULATE EXPERIMENTALLY INDUCED OEDEMA IN THE RAT PAW
Authors: LEWIS A.J. , NELSON D.J. , SUGRUE M.F. 
Published: July 2012

Prostaglandins E1 and E2 but not prostaglandin F2α, arachidonic acid or linolenic acid, produced slight oedema when injected into the rat hindpaw.
Prostaglandin E1 potentiated hindpaw oedema produced by carrageenan, kaolin, bradykinin and trypsin but not that produced by 5‐hydroxytryptamine (5‐HT), histamine, dextran B or compound 48/80. Carrageenan‐ and bradykinin‐induced paw oedemas were also potentiated by prostaglandin E2. Arachidonic acid potentiated responses to carrageenan and kaolin but not responses to bradykinin, trypsin, 5‐HT, histamine, dextran B or compound 48/80. Linolenic acid did not potentiate hindpaw oedema induced by carrageenan.
Potentiation of carrageenan‐induced oedema by prostaglandin E1 was not diminished by pretreatment with indomethacin, hydrocortisone or cyproheptadine. However, arachidonic acid potentiation of carrageenan oedema was reduced by pretreatment with non‐steroidal anti‐inflammatory drugs but not by anti‐inflammatory steroids or by paracetamol.
The enhancement of the response to carrageenan and kaolin by prostaglandins E1, E2 and arachidonic acid is discussed in terms of kinin mediation.
DESENSITIZATION IN THE INNERVATED AND IN THE CHRONICALLY DENERVATED SOLEUS MUSCLE OF THE MOUSE
Authors: HALL MOIRA T. , MALEQUE M.A. , WADSWORTH R.M. 
Published: July 2012

A study was made of desensitization in chronically denervated and in normally innervated mouse soleus muscles.Very high concentrations of acetylcholine produced small contractions of the innervated muscles; these were reduced in size when the addition was repeated 1 min after wash‐out.Desensitization in innervated muscles was receptor specific: contractions in response to KCl and caffeine were not reduced following acetylcholine, nor did KCl produce desensitization.In chronically denervated muscles non‐specific desensitization was observed if acetylcholine was added in the presence of low concentrations of acetylcholine or carbachol. Contractions to KCl but not to caffeine were reduced. KCl produced a similar kind of desensitization.After washing out moderate or supramaximal concentrations from the chronically denervated muscle no desensitization was observed. However, 1 min after washout of very high concentrations the muscle was non‐specifically desensitized.It is concluded that relatively high concentrations of acetylcholine are required to produce specific desensitization in the soleus muscle. Chronically denervated muscles, being supersensitive, show non‐specific loss of sensitivity with concentrations of acetylcholine too low to produce specific desensitization.
PARALLEL BIOASSAY OF BOMBESIN AND LITORIN, A BOMBESIN‐LIKE PEPTIDE FROM THE SKIN OF Litoria aurea
Authors: ENDEAN R. , ERSPAMER V. , ERSPAMER G. FALCONIERI , IMPROTA G. , MELCHIORRI P. , NEGRI L. , SOPRANZI N. 
Published: July 2012

The spectrum of biological activity exhibited by litorin, a bombesin‐like nonapeptide found in extracts of the skin of the Australian leptodactylid frog Litoria aurea was compared with that exhibited by the tetradecapeptide bombesin.
Litorin proved to be more potent than bombesin on isolated smooth muscle preparations and on the urinary bladder in situ. However, it was less potent on dog systemic blood pressure and kidney vasculature, activation of the renin‐angiotensin system being slight or lacking.
Gastrin release and acid secretion produced by litorin was more rapid in onset but less intense and less sustained than that elicited by bombesin. The same could be observed for pancreatic secretion.
Gall bladder contraction stimulated by litorin was probably caused by a double action of the peptide, directly on the bladder smooth muscle, and indirectly by cholecystokinin release.
In its effects on the myo‐electric activity of the dog duodenum (inhibition of spikes and increase in frequency of pacesetter potentials leading to the appearance of a sequence of slow and small potentials) litorin possessed approximately 50 to 70% of the activity of bombesin.
ANTAGONISM OF γ‐AMINOBUTYRIC ACID AND GLYCINE BY CONVULSANTS IN THE CUNEATE NUCLEUS OF CAT
Authors: HILL R.G. , SIMMONDS M.A. , STRAUGHAN D.W. 
Published: July 2012

Some convulsant substances have been applied to single neurones in the cat cuneate nucleus by microiontophoresis. Numerical values were derived for the effectiveness and selectivity of the substances as antagonists of γ‐aminobutyric acid (GABA) and glycine.
(+)‐Bicuculline methochloride was the most effective GABA antagonist and it also excited many neurones. It antagonized GABA in 93% of experiments but also antagonized glycine in 41% of experiments. In most experiments the antagonism of GABA was greater than the antagonism of glycine resulting in an overall selective antagonism of GABA that was statistically significant. Nevertheless, in only about one quarter of the individual experiments was the GABA antagonism substantial and the selectivity clearcut.
(+)‐Bicuculline and picrotoxin were less easily applied to neurones by microiontophoresis and were found to antagonize GABA in 30% and 35% of experiments, respectively. They also antagonized glycine in 25% and 30% of experiments, respectively. Overall, neither substance could be shown to be selective, statistically, although in the few individual experiments where the GABA antagonism was substantial the antagonism was clearly selective.
(+)‐Tubocurarine antagonized GABA in 59% and glycine in 32% of experiments and it also excited many neurones. Penicillin antagonized GABA in 33% of experiments without antagonizing glycine. Neither antagonist caused any substantial antagonisms of GABA and neither showed significant selectivity overall. (—)‐Bicuculline methochloride, leptazol and bemegride antagonized GABA or glycine in less than 10% of experiments, although (—)‐bicuculline methochloride excited most neurones.
Strychnine antagonized glycine in every experiment while antagonizing GABA in only 5% of experiments. In each individual experiment the antagonism of glycine was substantial and clearly selective, resulting in a statistically significant selectivity overall.
It is concluded that the selective glycine antagonist strychnine is considerably better than the presently available GABA antagonists for distinguishing between responses to GABA and glycine, when the antagonists are applied by microiontophoresis.
STEREOSELECTIVE BINDING IN CARDIAC TISSUE OF THE ENANTIOMERS OF BENZETIMIDE, AN ANTIMUSCARINIC DRUG
Authors: GRAY J.A. , LÜLLMANN H. , MITCHELSON F. , REIL G.‐H. 
Published: July 2012

Benzetimide, possessing two stable enantiomers, dexetimide and levetimide, has been investigated in guinea‐pig atria with respect to its atropine‐like action and its tissue distribution.
The antagonistic potency of dexetimide was found to be over 6000 times higher than that of levetimide, the pA2 values being 9.82 and 6.0 respectively.
The tissue accumulation was investigated for both isomers in the concentration range from 1.5 × 10−9 m to 10−6 M yielding tissue to medium ratios (T/M) of between approximately 50 and 10. The highest values were found for the lowest concentrations. At any concentration investigated, dexetimide exhibited a higher uptake than the levoisomer.
The rate of uptake and washout of dexetimide was extremely slow, that of levetimide being considerably faster at equimolar concentrations. The same pattern held true for the onset and decline of the antagonistic action.
The high accumulation was found to be almost entirely due to unspecific binding. Even in the case of dexetimide the relative size of the receptor compartment could not be determined. The unspecific binding sites displayed a certain stereoselectivity but to a much lesser extent than the specific receptor binding sites.
IDENTIFICATION OF SEPARATE RECEPTORS FOR ADENOSINE AND ADENOSINE 5′‐TRIPHOSPHATE IN CAUSING RELAXATIONS OF THE ISOLATED TAENIA OF THE GUINEA‐PIG CAECUM
Authors: SPEDDING M. , WEETMAN D.F. 
Published: July 2012

The mechanisms by which adenosine 5′‐triphosphate (ATP), adenosine 5′‐diphosphate (ADP), adenosine 5′‐monophosphate (AMP) and adenosine relax the taenia caecum preparation of the guinea‐pig have been studied. ATP and ADP produced similar effects which were qualitatively different from those of AMP and adenosine.
2‐2′Pyridylisatogen tosylate (PIT: 50 μm for 30 min) blocked the effects of ATP and ADP, but exhibited weak activity against AMP and failed to antagonize the effects of adenosine. The action of PIT was unaffected by the inclusion of dipyridamole (2 μm) in the bathing fluid.
There was a significant correlation between the sensitivity of individual preparations to ATP or ADP and the blocking potency of PIT.
The presence of adenosine in the bathing fluid (2 mm for > 30 min) desensitized the taenia to subsequent applications of adenosine. The effects of ATP were increased by this procedure.
The results indicate that ATP and adenosine relax the taenia by different mechanisms.
AN IRREVERSIBLE EFFECT OF LITHIUM ADMINISTRATION TO PATIENTS
Authors: LINGSCH C. , MARTIN K. 
Published: July 2012

Lithium administration to patients leads to a pronounced inhibition (about 90%) of the choline transport system in erythrocytes. The transport system does not recover when ghosts are prepared from the erythrocytes, thereby removing intracellular as well as extracellular lithium.
When a patient is taken off lithium, the choline transport in erythrocytes recovers only very slowly over a period of three months, i.e. at about the same rate at which the erythrocytes that had been exposed to lithium are replaced by new cells.
It is concluded that therapeutic concentrations of lithium produce an irreversible inhibition of the choline transport system in human erythrocytes.
THE PHARMACOLOGY OF ANAPHYLAXIS IN THE CHICKEN INTESTINE
Authors: CHAND N. , EYRE P. 
Published: July 2012

The Schultz‐Dale phenomenon has been demonstrated in several circular smooth muscle strips of oesophagus, crop, duodenum, jejunum and ileum taken from young and adult domestic fowl sensitized actively to crystalline bovine albumin or horse plasma.The ileal strips contract to acetylcholine, histamine, 5‐hydroxytryptamine (5‐HT), prostaglandins E1, E2, F2α, bradykinin and bovine slow reacting substance of anaphylaxis (SRS‐A). Marked seasonal and individual variations in the responsiveness of gut tissues to these exogenous agonists were noted.Antagonism of contractions to histamine by mepyramine suggests the existence of H1‐histamine receptors in chicken ileum. Blockade of 5‐HT‐induced contractions by methysergide shows the preponderance of ‘D’‐musculotropic tryptamine receptors.Failure of selective receptor antagonists of acetylcholine, histamine and 5‐HT to modify the Schultz‐Dale reaction suggests the nonparticipation of aminergic mechanisms in this reaction.Partial to complete blockade of the Schultz‐Dale reaction by a prostaglandin receptor antagonist (polyphloretin phosphate, PPP); prostaglandin synthetase inhibitors (sodium meclofenamate and phenylbutazone); inhibitors of synthesis and release of histamine and SRS‐A (PR‐D‐92‐EA, M&B 22948, diethylcarbamazine citrate, and PPP) and an inhibitor of proteinases (aprotinin) strongly suggests the involvement of vasoactive lipids and polypeptides in the anaphylactic response of chicken ileum to specific antigen.
CIRCULATORY EFFECTS OF ORAL AND SUBCUTANEOUS ADMINISTRATION IN NORMAL SUBJECTS OF A NEW BRONCHODILATOR, IBUTEROL, A PRO‐DRUG TO TERBUTALINE
Authors: HÖGLUND ELIN , WESTLING H. , WHITE T. 
Published: July 2012

The di‐isobutyryl ester of terbutaline, ibuterol, was given subcutaneously and orally to healthy volunteers and its effects on heart rate, arterial blood pressure, and ECG were compared with those of terbutaline itself. The effects of the two substances were qualitatively identical, but quantitatively different.By mouth, ibuterol acted more rapidly, and was 2–3 times more active. After intramuscular injection, ibuterol caused less increase in local blood flow than terbutaline.Ibuterol can be regarded as a pro‐drug, which in itself has little activity, but which can be made active in the body.
HYPOTENSION IN RABBITS INFECTED WITH Trypanosoma brucei
Authors: BOREHAM P.F.L. , WRIGHT I.G. 
Published: July 2012

Blood pressures and heart rates of 12 anaesthetized rabbits chronically infected with T. brucei were measured (average infection time 39 days (range 25–67)). The systolic BP was 31.4 ± 5.7 mmHg, the diastolic BP 25.0 ± 7.2 mmHg, and the heart rate 120.5 ± 24.2 beats/minute. Two rabbits were already hypotensive 10 days after infection. In 12 anaesthetized control rabbits, the systolic BP was 66.2 ±7.3 mmHg (mean ± s.e.), the diastolic BP 60.2 ± 7.3 mmHg, and the heart rate 116.3 ±15.9 beats/minute.
The intravenous injection of 3 × 108 disintegrated trypanosomes into infected rabbits lowered the blood pressure by 41.4 ± 22.0%. Pretreatment of two rabbits with aprotinin prior to administration of parasites prevented the fall in blood pressure.
Injection of 3 × 108 live trypanosomes complexed with hyperimmune sera produced a fall of 68.3 ± 38.4% in the systolic BP of normal rabbits. Disintegrated or live trypanosomes, or hyperimmune sera alone had no effect. Pretreatment of animals with aprotinin prior to administration of the immune complex abolished the fall in BP.
The results suggest that the profound hypotension in chronic trypanosomiasis is caused by complex formation of trypanosomes with antibody. Since it can be prevented by pretreatment with aprotinin, it is likely that activation of plasma kallikrein with a subsequent release of plasma kinins contributes to this effect.
PHARMACOLOGICAL PROPERTIES OF N‐(3′,4′‐DIMETHOXYCINNAMOYL) ANTHRANILIC ACID (N‐5′), A NEW ANTI‐ATOPIC AGENT
Authors: AZUMA H. , BANNO K. , YOSHIMURA T. 
Published: July 2012

N‐(3′,4′‐dimethoxycinnamoyl) anthranilic acid (N‐5′) exhibited a dose‐dependent, potent inhibition of the passive cutaneous anaphylaxis (PCA) mediated by homocytotropic antibodies (HTA), which was hardly affected by anti‐inflammatory agents such as phenylbutazone, indomethacin and prednisolone at any dose used. The HTA‐induced PCA was significantly inhibited by combined treatment with diphenhydramine and cyproheptadine.
Doses of N‐5′ which potently inhibited HTA‐induced PCA inhibited only slightly the heterologous PCA produced by anti‐bovine serum albumin (BSA) rabbit serum. This heterologous PCA was clearly inhibited by phenylbutazone, indomethacin and prednisolone. Diphenhydramine and cyproheptadine, singly or combined inhibited the heterologous PCA only slightly.
The increased vascular permeability caused by histamine and 5‐hydroxytryptamine was significantly inhibited by diphenhydramine or cyproheptadine, but not by N‐5′ and the anti‐inflammatory agents used.
N‐5′ 150 mg/kg orally inhibited rat paw oedema induced by carrageenin by about 26% while phenylbutazone, indomethacin and prednisolone produced significant inhibition.
N‐5′ at concentrations of 100 and 1000 μm significantly inhibited (by about 52% and 95%, respectively) the histamine release from rat peritoneal cells induced by HTA; 10 μm N‐5′ had little effect. Histamine release was inhibited by phenylbutazone or indomethacin at 1000 μm but not at 100 μm. Prednisolone had no effect on histamine release at any of the concentrations used.
These findings suggest that the inhibition of the HTA‐induced PCA by N‐5′ may be due to inhibition of histamine release and is clearly different from the actions of anti‐inflammatory agents such as phenylbutazone, indomethacin and prednisolone.