bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE DISTRIBUTION OF ADRENOCEPTORS AND OTHER DRUG RECEPTORS BETWEEN THE TWO ENDS OF THE RAT VAS DEFERENS AS REVEALED BY SELECTIVE AGONISTS AND ANTAGONISTS
Authors: MacDONALD A. , McGRATH J.C. 
Published: July 2012

The effects of adrenoceptor agonists and other agonists on the contractile responses of the prostatic and epididymal portions of the rat isolated vas deferens to single pulse field stimulation were investigated.
α‐Adrenoceptor agonists produced prejunctional α2‐mediated inhibition and post‐junctional α1‐mediated potentiation of the nerve‐induced responses. Guanabenz and xylazine produced mainly inhibitory effects, xylazine being 10 times less potent. Clonidine and oxymetazoline produced inhibition with similar potency to guanabenz but at higher concentrations excitatory effects were present, particularly in the epididymal portion. Phenylephrine produced only potentiation of the nerve‐induced response in both portions. Potentiation of nerve‐induced responses was a more sensitive and quantitative index of excitation than was direct contraction of the tissue.
Isoprenaline and salbutamol both gave β2‐mediated inhibition of the nerve‐induced responses in both portions of tissue. At least part of the effect was post‐junctional since phenylephrine contractions were inhibited. Isoprenaline also produced a post‐junctional α1‐mediated excitation.
Noradrenaline produced effects qualitatively similar to those of the other α‐adrenoceptor agonists, inhibition and excitation predominating in the prostatic and epididymal ends respectively.
Morphine produced inhibition in the mouse but not in the rat vas deferens. In rat vas, however, enkephalin analogues produced pre‐junctional inhibition of responses in both portions which could be partly reversed by naloxone; restoration of the adrenergic component was more complete. Rat anococcygeus showed no equivalent effect.
Adenosine 5′‐triphosphate (ATP) inhibited nerve‐induced responses in each portion with a greater effect on the prostatic portion.
EFFECT OF INDOMETHACIN ON HYDRALAZINE‐INDUCED RENIN AND CATECHOLAMINE RELEASE IN THE CONSCIOUS RABBIT
Authors: CAMPBELL WILLIAM B. , GRAHAM ROBERT M. , JACKSON EDWIN K. , LOISEL DANIEL P. , PETTINGER WILLIAM A. 
Published: July 2012

The effects of hydralazine on mean arterial pressure (MAP) heart rate (HR), plasma renin activity (PRA) and plasma catecholamines were examined in conscious rabbits before and after prostaglandin synthesis inhibition with indomethacin.
Hydralazine (3 mg/kg, i.v.) produced a 12% decrease in MAP and significant increases in HR, PRA and plasma noradrenaline and adrenaline.
Indomethacin (5 mg/kg, s.c.) failed to alter significantly the control MAP, HR, PRA or plasma catecholamines but inhibited renal venous prostaglandin E2 by 56% (P < 0.02).
Indomethacin inhibited the hydralazine‐induced tachycardia by 24% and augmented its hypotensive effects by 6%.
The hydralazine‐stimulated increase in PRA was also inhibited 75% (P < 0.001) by indomethacin whereas noradrenaline and adrenaline concentrations were not significantly reduced.
Indomethacin inhibits hydralazine‐induced renin release in the presence of elevated concentrations of plasma catecholamines; these findings suggest that renal prostaglandins function as important mediators of sympathetically‐induced renin release.
EFFECT OF LOW‐DOSE LITHIUM ADMINISTRATION AND SUBSEQUENT WITHDRAWAL ON BIOGENIC AMINES IN RAT BRAIN
Authors: AHLUWALIA P. , SINGHAL R.L. 
Published: July 2012

The effects of low‐dose lithium administration (2 mEq/kg, daily) and its subsequent withdrawal have been examined with reference to changes in biogenic amine systems in several discrete regions of rat brain.
Increased levels of striatal tyrosine and midbrain tryptophan were found following lithium administration together with slight decreases in striatal tyrosine hydroxylase and midbrain tryptophan hydroxylase activities. Withdrawal resulted in a decrease in tyrosine content with increased tyrosine hydroxylase activity, whilst tryptophan levels and tryptophan hydroxylase activity were increased.
Lithium treatment and withdrawal resulted in altered levels of noradrenaline and dopamine, these changes being regionally variable. 3‐Methoxy‐4‐hydroxyphenylglycol content was depressed in both treated and withdrawal rats as were 3,4‐dihydroxyphenylacetic acid levels. Homovanillic acid decreased as a result of lithium treatment, but was greatly elevated in the withdrawal group.
5‐Hydroxytryptamine content decreased in some brain regions following lithium treatment with return towards control values in withdrawal rats. 5‐Hydroxyindoleacetic acid levels also displayed a regional variation as a result of lithium treatment and withdrawal.
The implications of these observations in elucidating the pharmacological effect of lithium treatment and its subsequent withdrawal are discussed.
INHIBITION BY NICOTINE OF THE FORMATION OF PROSTACYCLIN‐LIKE ACTIVITY IN RABBIT AND HUMAN VASCULAR TISSUE
Authors: SONNENFELD T. , WENNMALM Å. 
Published: July 2012

Rings of vascular tissue (from rabbit aorta or human peripheral vein) were incubated at room temperature in Tyrode solution in the absence or presence of nicotine or indomethacin.
Addition of portions of the incubates to human platelet‐rich plasma (HPRP) elicited a decrease in adenosine 5′‐diphosphate (ADP)‐induced platelet aggregation in this plasma. Authentic prostacyclin (PGI2) also induced such a decrease. The decreased aggregation amplitudes that followed the addition of the vascular tissue incubates and of PGI2 were equally potentiated by theophylline (10−4 m).
Both nicotine and indomethacin counteracted the formation of platelet anti‐aggregatory activity in the vascular tissue incubates. The IC50s of nicotine and of indomethacin on the formation of platelet antiaggregatory activity were 2 times 10−5 m and 6 times 10−6 m, respectively.
Nicotine failed to affect the platelet anti‐aggregatory effect induced by authentic PGI2 in HPRP.
It is concluded that nicotine counteracts the formation of platelet anti‐aggregatory activity in rabbit aorta and human peripheral vein by eliciting an inhibitory effect on the bioformation of prostacyclin in these types of vascular tissue.
EVALUATION OF ANTAGONISM OF ACONITINE‐INDUCED DYSRHYTHMIAS IN MICE AS A METHOD OF DETECTING AND ASSESSING ANTIDYSRHYTHMIC ACTIVITY
Authors: WINSLOW EILEEN 
Published: July 2012

Antagonism of aconitine‐induced dysrhythmias in mice as a method of detecting and assessing antidysrhythmic activity was evaluated.
Aconitine‐induced dysrhythmias in mice appear to be selectively sensitive to antidysrhythmic agents (administered intraperitoneally) which reduce the inward sodium current in cardiac cells.
Antidysrhythmic agents whose mechanism of action is thought to depend on β‐adrenoceptor blockade, prolongation of cardiac monophasic action potentials or calcium antagonism are ineffective in delaying the onset of aconitine‐induced dysrhythmias in mice. The inactive drugs were practolol, sotalol, bretylium, amiodarone and verapamil.
Comparisons of anti‐dysrhythmic activities of test drugs should be based on more than one ED value and should take account of efficacy as well as potency.
The mouse aconitine test is a useful and rapid method of evaluating oral antidysrhythmic activity in terms of potency, efficacy and duration of action.
With respect to potency, efficacy, oral activity, duration of action and safety, 3α‐amino‐5α‐androstan‐2β‐ol‐17‐one hydrochloride (Org 6001) offered the most satisfactory overall profile of the active drugs tested (Org 6001, aprindine, quinidine, disopyramide, lignocaine, mexiletine, procainamide and propranolol).
ANTAGONISM BY FENAMATES OF PROSTAGLANDIN ACTION IN GUINEA‐PIG AND HUMAN ALIMENTARY MUSCLE
Authors: BENNETT A. , PRATT D. , SANGER G.J. 
Published: July 2012

Low concentrations of meclofenamate, flufenamate or mefenamate had little effect on contractions in response to acetylcholine in any tissue studied.
Sodium meclofenamate potently antagonized contractions of guinea‐pig ileum longitudinal muscle to prostaglandin E2 (PGE2), PGF2α or PGD2.
In guinea‐pig colonic longitudinal muscle, contractions to PGE2 were reduced by sodium meclofenamate, but contractions of the longitudinal or circular muscle to PGF2α or PGD2 were less effectively inhibited.
In human gastrointestinal longitudinal muscle, sodium meclofenamate or flufenamate potently inhibited contractions to PGF2α, but not to PGE2.
Sodium mefenamate or mefenamic acid, even in high concentrations, had little effect on contractions to PGF2α, but tended to inhibit PGE2‐induced contractions of human gastrointestinal longitudinal muscle.
The therapeutic advantages of prostaglandin synthesis inhibitors which also antagonize responses to certain prostaglandins are discussed.
THE EFFECT OF SODIUM SALICYLATE ON CEREBRAL BLOOD FLOW AND METABOLISM
Authors: PICKARD J.D. , ROSE J.E. , SHAW M.D.M. , STRATHDEE ANN 
Published: July 2012

The effect of intravenous sodium salicylate on cerebral oxygen consumption and cerebral blood flow and its response to hypercapnia was measured by the 133Xenon intracarotid injection technique in ten baboons.
After an initial peak, the plasma salicylate level maintained a stable value for 2 h of 1 mmol/l with 50 mg/kg sodium salicylate and 2.5 mmol/l with 200 mg/kg sodium salicylate.
Sodium salicylate (50 mg/kg) produced no change in baseline cerebral blood flow (CBF) or cerebral oxygen consumption (CMRO2) but the CBF response to hypercapnia was reduced by 41% during the first hour. During the second hour after salicylate administration, CMRO2 increased by 26%, CBF at normocapnia increased by 31% and the CBF response to hypercapnia was 67% of the baseline value.
Sodium salicylate (200 mg/kg) increased CMRO2 by 65%. There was no significant change in CBF at normocapnia or hypercapnia.
These results confirm that inhibitors of prostaglandin synthesis, which can cross the blood brain barrier in sufficient quantity, reduce the response of the cerebral circulation to hypercapnia. The difficulties in interpreting changes in the CBF CO2 response in the presence of increases in CMRO2 are discussed. It is suggested that the respiratory stimulation seen in salicylate intoxication is the result of a central metabolic stimulation.
SUBACUTE CANNABINOID TREATMENT: ANTICONVULSANT ACTIVITY AND WITHDRAWAL EXCITABILITY IN MICE
Authors: KARLER RALPH , TURKANIS STUART A. 
Published: July 2012

The effects of subacute treatment with cannabidiol, Δ9‐tetrahydrocannabinol (Δ9‐THC), phenytoin and phenobarbitone on anticonvulsant activity and on withdrawal excitability in mice were compared in three electrically induced seizure‐threshold tests.
In the maximal electroshock‐threshold test, subacute treatment did not alter the anticonvulsant activity of cannabidiol, phenytoin or phenobarbitone, but tolerance developed to Δ9‐THC.
In the 60 Hz electroshock‐threshold test, the activity of Δ9‐THC and cannabidiol did not change, but tolerance developed to phenobarbitone, and there was an increase in sensitivity to phenytoin.
In the 6 Hz electroshock‐threshold test, there was an increase in sensitivity to both Δ9‐THC and cannabidiol, there was tolerance to phenobarbitone, while the activity of phenytoin did not change.
Although tolerance developed in some of the seizure‐threshold tests to Δ9‐THC and phenobarbitone, tolerance to cannabidiol and phenytoin did not develop in any of the tests.
Hyperexcitability followed withdrawal from only Δ9‐THC (6 Hz and 60 Hz electroshock‐threshold tests) and phenobarbitone (maximal electroshock‐threshold and 60 Hz electroshock‐threshold tests).
The Δ9‐THC withdrawal hyperexcitability suggests that the use of marihauana may jeopardize the control of seizures in epileptics.
THE BINDING OF SOME ANTIDEPRESSANT DRUGS TO BRAIN MUSCARINIC ACETYLCHOLINE RECEPTORS
Authors: GOLDS P.R. , PRZYSLO F.R. , STRANGE P.G. 
Published: July 2012

The binding of some antidepressant drugs, including some new drugs of atypical structure (flupenthixol, iprindole, maprotiline, mianserin, nomifensine, tofenacine and viloxazine) to muscarinic acetylcholine receptors in the brain has been studied by displacement of [3H]‐atropine.
Many of the drugs are potent muscarinic antagonists.
Some correlation can be made between the affinity for binding to the muscarinic acetylcholine receptor and the incidence of anticholinergic side effects in clinical usage.
MORPHINE‐THEOPHYLLINE INTERACTION: ANTAGONISM OR FACILITATION?
Authors: BRAILOWSKY SIMÓN , GUERRERO‐MUN̆OZ FEDERICO , LUJÁN MIGUEL , SHKUROVICH MARIO 
Published: July 2012

Morphine‐theophylline interactions were investigated in both acute and narcotic‐dependent preparations, in vitro and in vivo, using four different experimental models: LD50 doses of morphine and naloxone in the mouse; naloxone‐induced contractions in the electrically‐stimulated and opiate‐dependent isolated ileum of the guinea‐pig; naloxone‐induced jumps in the mouse; and calcium uptake in synaptosomal preparations.
The LD50 of morphine was significantly increased by theophylline.
The lethal effect of theophylline was potentiated by pretreatment of the animals with naloxone.
Theophylline displayed protective effects in the inhibitory response to morphine and antagonism to the withdrawal response induced by naloxone in the electrically‐stimulated isolated ileum of the guinea‐pig.
The number of jumps induced by naloxone in morphine‐dependent mice was significantly diminished by theophylline.
The inhibitory effect of morphine on the synaptosomal uptake of calcium was decreased by theophylline.
The effects of both morphine and theophylline on the cyclic nucleotides and the possible role of calcium in these actions are discussed.
EFFECTS OF CYCLIC AMP‐ AND CYCLIC GMP‐PHOSPHODIESTERASE INHIBITORS ON IMMUNOLOGICAL RELEASE OF HISTAMINE AND ON LUNG CONTRACTION
Authors: FROSSARD N. , LANDRY Y. , PAULI G. , RUCKSTUHL M. 
Published: July 2012

Cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP)‐ and cyclic guanosine 3′, 5′‐monophosphate (cyclic GMP)‐phosphodiesterase activities from rat lung were selectively inhibited by ZK 62711 and M & B 22948, respectively. Theophylline and papaverine inhibited both activities.
Rat lung strips contracted by carbachol were relaxed by 4‐(3‐cyclopentyloxy‐4‐methoxyphenyl)‐2‐pyrrolidone (ZK 62711, EC25 = 7 × 10−8m) and 2‐O‐propoxyphenyl‐8‐azapurin‐6‐one (M&B 22948, EC25 = 5 × 10−7m) indicating relaxant properties of both cyclic AMP and cyclic GMP.
The antigen‐induced histamine release from human basophils was inhibited by ZK 62711 (IC25 = 8 × 10−7m), whereas M&B 22948 had no effect. On the contrary, the release from rat mast cells was inhibited by M&B 22948 (IC25 = 10_6m), while ZK 62711 had no effect.
These data show an inhibitory effect of cyclic AMP on histamine release to be involved with basophils, whereas cyclic GMP is predominantly involved with mast cells. It is suggested that the antianaphylactic properties of cyclic nucleotide phosphodiesterase inhibitors are mainly linked to the increase of cyclic GMP.
NON‐ADRENERGIC, NON‐CHOLINERGIC INNERVATION IN MONKEY AND HUMAN CEREBRAL ARTERIES
Authors: TODA NOBORU 
Published: July 2012

Transmural electrical stimulation (0.5 to 20 Hz) and nicotine (10−4 m) produced relaxations of helically‐cut strips of monkey and human cerebral arteries, contracted with prostaglandin F2α.
The relaxation induced by electrical stimulation was suppressed or abolished by tetrodotoxin, while the nicotine‐induced relaxation was abolished by hexamethonium but was unaffected by tetrodotoxin. Both relaxations were not attenuated by β‐adrenoceptor antagonists and atropine.
These findings may indicate that large cerebral arteries of the monkey and man are innervated by non‐adrenergic, non‐cholinergic nerves, excitation of which liberates unknown vasodilator substance(s).
ACTIONS OF VARIOUS MUSCARINIC AGONISTS ON MEMBRANE POTENTIAL, POTASSIUM EFFLUX, AND CONTRACTION OF LONGITUDINAL MUSCLE OF GUINEA‐PIG INTESTINE
Authors: BOLTON T.B. , CLARK J.R 
Published: July 2012

Depolarizations were recorded intracellularly in smooth muscle from the taenia of the guinea‐pig caecum in response to the iontophoretic application of acetylcholine, carbachol, oxotremorine‐M, methylfurmethide, hexyl trimethylammonium and tetramethylammonium (TMA).
No differences between the iontophoretic responses to agonists stable to cholinesterase were detected.
The latency and time to peak of acetylcholine‐induced depolarizations were less than those to stable agonists, and the response was briefer and less complex in shape. These differences were reduced, or disappeared, upon inhibition of cholinesterase.
The rate of loss of 42K and changes in length were measured in superfused strips weighing about 10 mg of separated longitudinal muscle of guinea‐pig ileum.
Acetylcholine, carbachol, methylfurmethide, butyltrimethylammonium and TMA contracted the muscle and increased the rate of loss of 42K.
Contrary to previous reports, no evidence of a selective action of any of these agonists on 42K loss was detected. TMA appeared to be a partial agonist in evoking 42K loss, although it produced a maximum contraction.
The maximum 42K efflux produced by acetylcholine was about 40% of the maximum evoked by application of carbachol or methylfurmethide. If cholinesterase was inhibited, the 42K efflux evoked by maximally effective concentrations of acetylcholine was comparable to that evoked by a stable agonist.
These results are consistent with the idea that the muscarinic agonists used interact in an essentially similar way with muscarinic receptors to produce their effects on membrane potential, permeability, and tension.
ACTIONS OF THE CRUDE VENOM OF THE SYDNEY FUNNEL‐WEB SPIDER, Atrax robustus ON AUTONOMIC NEUROMUSCULAR TRANSMISSION
Authors: HARRIS J.B. , SUTHERLAND S. , ZAR M.A. 
Published: July 2012

The effects on mammalian autonomic neuromuscular transmission of the crude venom of the female Sydney funnel‐web spider Atrax robustus, have been investigated.
At doses of 10 μg/ml or lower the indirectly elicited twitch‐like responses of the rat anococcygeus preparation were inhibited. At doses greater than 10 μg/ml there was an initial reduction in the twitch‐like response followed by a sustained contracture of the tissue.
The long‐lasting contracture caused by the venom was abolished by the application of phentolamine. It was virtually non‐existent in muscle preparations isolated from reserpine‐treated rats.
In the presence of tetrodotoxin the contracture was smaller and less well maintained than in its absence.
The venom caused a small reduction in the amplitude of the indirectly elicited twitch‐like response of the longitudinal muscle of the guinea‐pig ileum, followed by an increase in the tone of the preparation. The increase in tone was maintained for several minutes and was rapidly abolished by the application of atropine. The presence of venom did not affect control responses to either histamine or acetylcholine.
Inhibitory transmission in the rat anococcygeus preparation was unaffected by the venom.
The neurally‐mediated twitch‐like responses of both guinea‐pig and rat vas deferens were inhibited by the venom at doses below 10 μg/ml. At higher doses the inhibition was accompanied by spontaneous contractions, and at doses in excess of 100 μg/ml the inhibition of twitch‐like responses was transient and was followed by a potentiation of the motor response and extensive spontaneous activity. The preparation became quiescent 20 min after the application of venom and the evoked response was abolished after 60 min.
The venom had qualitatively similar effects on motor transmission in the human vas deferens as on the rat and guinea‐pig preparations. However, the human preparations were 50 to 100 times more sensitive to the effects of the venom.
SELECTIVE DEPRESSION OF SYNAPTIC EXCITATION IN CAT SPINAL NEURONES BY BACLOFEN: AN IONTOPHORETIC STUDY
Authors: DAVIES JOHN 
Published: July 2012

The effects of baclofen have been examined on responses of neurones in the spinal cord of the anaesthetized cat to stimulation of appropriate synaptic pathways, acetylcholine and a range of amino acid excitants. Baclofen and excitant substances were administered by standard microiontophoretic techniques.
Small ejecting currents of baclofen (<10 na) depressed non‐cholinergic, excitatory, synaptic responses evoked by stimulation of dorsal roots or muscle or cutaneous afferents. Excitatory monosynaptic responses were particularly sensitive to the depressant action of baclofen.
Spontaneous firing in neurones was sometimes reduced in parallel with synaptic excitatory responses, but synaptically evoked inhibition was unaffected and ventral root evoked excitation of Renshaw cells was either unaffected or enhanced by baclofen.
Ejecting currents of baclofen which markedly depressed excitatory synaptic responses either had no effect or minimal depressant effects on responses induced by iontophoretically administered acetylcholine and excitant amino acids. However, relatively large currents of baclofen (e.g. 20 to 40 na) reduced excitatory responses to exogenously administered excitants.
It is suggested that baclofen depresses (a) synaptic response by an action on excitatory nerve terminals and (b) responses to exogenous excitants via a postsynaptic action.
Comparison of baclofen with a number of other substances indicates that the depression of noncholinergic, excitatory, synaptic responses is unlikely to involve an interaction of this agent with receptors for monoamines, 5‐hydroxytryptamine or the inhibitory amino acids, γ‐aminobutyric acid and glycine.
INSULIN‐INDUCED ENHANCEMENT OF UPTAKE OF NORADRENALINE IN ATRIAL STRIPS
Authors: BHAGAT B. , BURKE W.J. , DHALLA N.S. 
Published: July 2012

Addition of insulin to the organ bath increased the force of contraction of guinea‐pig left atrial strips driven electrically at 1 Hz
The positive inotropic response to insulin remained unaltered in atria depleted of catecholamine or when β‐adrenoceptors were blocked by addition of propranolol to the organ bath
The response of isolated atria to noradrenaline was significantly reduced in the presence of insulin
Insulin affected neither the calcium accumulating abilities of the heart sarcolemma, mitochondria or microsomes, nor the cyclic adenosine 3′, 5′‐monophosphate (cyclic‐AMP)‐protein kinase‐induced stimulation of microsomal calcium uptake
Addition of insulin to the organ bath enhanced significantly the ability of the cardiac tissue to take up [3H]‐noradrenaline as well as [3H]‐metaraminol. The activities of monoamine oxidase and catechol‐O‐methyl transferase were not changed after addition of insulin to homogenates of the heart
The ability of insulin to facilitate uptake of noradrenaline would be expected to cause a decrease in the amount of the amine reaching the receptors, thus leading to a diminished response to this amine. This may explain, at least in part, insulin‐induced subsensitivity to noradrenaline
This view is supported by the observation that after blockade of amine uptake by destruction of nerve terminals, insulin failed to reduce the positive inotropic response to noradrenaline.
THE INFLAMMATORY EFFECTS OF HYDROPEROXY AND HYDROXY ACID PRODUCTS OF ARACHIDONATE LIPOXYGENASE IN RABBIT SKIN
Authors: HIGGS G.A. , SALMON J.A. , SPAYNE J.A. 
Published: July 2012

The inflammatory effects of hydroperoxy (HPETE) and hydroxy (HETE) acids, synthesized by arachidonic acid lipoxygenases, have been investigated in rabbit skin
High doses (10–20 μg) of 5‐, 12‐ or 15‐HPETE or the 5, 12‐di‐hydroxy acid, leukotriene B4 (0.1‐1 μg), caused small but significant increases in plasma exudation following intra‐dermal injection
Leukotriene B4 was equipotent with prostaglandin E2 and prostacyclin in potentiating bradykinin‐induced plasma exudation, and was 100 times more active in this property than any other lipoxygenase product tested
Leukotriene B4‐induced plasma exudation was enhanced by prostaglandin E2
The mono‐HETEs were relatively inactive in causing or enhancing plasma exudation
Leukotriene B4 (0.1 μg) or prostaglandin E1 (1.0 μg) significantly elevated leukocyte accumulation in rabbit skin, whereas PGE2, 5‐HPETE, 5‐HETE, 12‐HPETE or 12‐HETE were inactive at doses up to 1 μg.