bluuebunny/crossref_metadata_2025_split huggingface dataset:
INHIBITORY ACTIONS OF CATECHOLAMINES ON ELECTRICALLY INDUCED CONTRACTIONS OF THE SUBMUCOUS PLEXUS‐LONGITUDINAL MUSCULARIS MUCOSAE PREPARATION OF THE GUINEA‐PIG OESOPHAGUS
Authors: KAMIKAWA YUICHIRO , SHIMO YASUO , UCHIDA KOHSUKE 
Published: July 2012

The submucous plexus‐longitudinal muscularis mucosae preparation of the guinea‐pig oesophagus was used to study the actions of catecholamines on the twitch responses to electrical stimulation.
When the preparation was stimulated coaxially (0.1 Hz, 0.5 ms, supramaximal voltage), stable twitch‐like contractions were obtained. These were abolished by tetrodotoxin (0.1 μm) and atropine (0.1 μm), potentiated by physostigmine (0.1 μm), and were mediated presumably by stimulation of intramural cholinergic nerves.
The twitch contractions of the muscularis mucosae were inhibited by catecholamines, in a concentration‐dependent manner. The order of potency was isoprenaline > adrenaline > noradrenaline > dopamine.
The inhibitory actions of noradrenaline (1 μm) and adrenaline (1 μm) were partly reversed by phentolamine (1 μm) or by propranolol (1$ mUM), and completely abolished by both antagonists together. The inhibitory effect of dopamine (300 μm)> was largely reversed by phentolamine (1 μm), but not by propranolol (1 μm), while the inhibitory action of isoprenaline was competitively antagonized only by propranolol (pA2 of 7.6).
The contraction of the muscularis mucosae to exogenously applied acetylcholine (ACh, 20 nM) which was comparable in magnitude with that to electrical stimulation was also inhibited by isoprenaline (0.1 μm), adrenaline (1 μm) and noradrenaline (1 μm), but not by dopamine (300 μm). In the presence of propranolol (1 μm), noradrenaline, adrenaline and dopamine potentiated the ACh‐induced contraction, while the effect of isoprenaline was mainly antagonized. The potentiating effects were antagonized by further treatment with phentolamine (1 μm).
Adrenaline, noradrenaline and dopamine but not isoprenaline, produced a weak contraction of the longitudinal muscularis mucosae in the presence of propranolol (3 μm). The contractile responses were completely inhibited by phentolamine (3 μm). Tone in the muscularis mucosae induced by carbachol (3 μm) in the presence of phentolamine (10 μm) was inhibited by catecholamines, in a concentration‐dependent manner, an effect that was competitively antagonized by propranolol.
In the submucous plexus‐longitudinal muscularis mucosae preparation of the guinea‐pig oesophagus there are three types of adrenoceptor, inhibitory prejunctional α‐adrenoceptors, excitatory postjunctional α‐adrenoceptors and inhibitory postjunctional β‐adrenoceptors, and cholinergic neurotransmission is inhibited by catecholamines acting at both prejunctional α‐ and postjunctional β‐adrenoceptors.
AGGREGATION OF RAT NEUTROPHILS BY NUCLEOTIDE TRIPHOSPHATES
Authors: FORD‐HUTCHINSON A.W. 
Published: July 2012

Adenosine 5′‐triphosphate (ATP) and uridine 5′‐triphosphate (UTP) at concentrations of 3 × 10−7 m and greater cause a rapid partially reversible aggregation of rat polymorphonuclear leucocytes.
Other neucleotide phosphates are much less active at producing aggregation responses; the agonist potencies being UTP > ATP > guanosine 5′‐triphosphate, cytidine 5′‐triphosphate, thymidine 5′‐triphosphate; ATP > adenosine 5′‐diphosphate (ADP) > adenosine 5′‐monophosphate (AMP); and ADP > uridine 5′‐diphosphate, thymidine 5′‐diphosphate, guanosine 5′‐diphosphate, cytidine 5′‐diphosphate. Adenosine is inactive.
The hydrolysis resistant analogues of ATP, α‐β‐methylene ATP and β‐γ‐methylene ATP, do not cause neutrophil aggregation suggesting that hydrolysis of ATP and UTP may be required to initiate the aggregation response.
It is postulated that ATP and UTP may be important stimulants of neutrophil function and may be involved in the adherence of these cells to the vascular endothelium.
EFFECT OF LIPID PEROXIDATION ON p‐AMINOHIPPURATE TRANSPORT BY RAT KIDNEY CORTICAL SLICES
Authors: FUJIMOTO YOHKO , FUJITA TADASHI 
Published: July 2012

The effect of lipid peroxidation on p‐aminohippurate transport by rat kidney slices was examined.
Ascorbic acid and Fe2+ promoted lipid peroxidation of rat renal cortical slices in a dose‐related manner.
Ascorbic acid (1.0 mM) and Fe2+ (0.4 mM) increased tissue water and decreased the accumulation of p‐aminohippurate.
The addition of N,N'‐diphenyl‐p‐phenylenediamine (antioxidant), at a concentration of 1 × 10−6m, completely inhibited the peroxidation and recovered the accumulation of p‐aminohippur ate.
The apparent Km of p‐aminohippurate uptake was increased by ascorbic acid and Fe2+ with no change in the apparent V.
These data suggest that ascorbic acid and Fe2+ can cause a significant alteration in p‐aminohippurate and water transport of renal cortical slices and that these effects can be correlated with lipid peroxidation.
A STUDY OF THE INHIBITORY EFFECTS OF SCH 28080 ON GASTRIC SECRETION IN MAN
Authors: ENE M.D. , KHAN‐DANESHMEND T. , ROBERTS C.J.C. 
Published: July 2012

SCH 28080 (2‐methyl‐8‐(phenyl methoxy) imidazo‐(1–2‐a) pyrine‐3‐acetonitrile) is a novel drug unrelated to existing anti‐ulcer agents.
The effect of placebo and increasing doses of the drug on gastric acid output and peptic activity was examined in four healthy men, in the resting state and following pentagastrin stimulation.
Significant inhibition of gastric acid secretion and peptic activity occurred with the 50 mg dose in both the stimulated and unstimulated states. Approximately 90% inhibition of acid output was achieved with the 200 mg dose.
Antisecretory activity of SCH 28080 is confirmed in man. This drug or an analogue may have potential in anti‐ulcer therapy.
EFFECTS OF 4‐AMINOPYRIDINE ON ACETYLCHOLINE OUTPUT FROM THE CEREBRAL CORTEX OF THE RAT in vivo
Authors: CASAMENTI FIORELLA , CORRADETTI R. , LÖFFELHOLZ K. , MANTOVANI P. , PEPEU G. 
Published: July 2012

The effects of 4‐aminopyridine (4AP) on the output of acetylcholine (ACh) from the cerebral cortex were investigated in unanaesthetized freely moving rats and in anaesthetized rats by means of the ‘cup technique’. ACh was determined by bioassay on the dorsal muscle of the leech.
In unanaesthetized rats intraperitoneal injection of 4AP (3 mg/kg) had no effect on the cortical output of ACh.
After injection of morphine (10 mg/kg s.c), which depressed the spontaneous output of ACh, 4AP increased the cortical output to a level significantly higher than that determined before morphine injection.
In rats anaesthetized with either urethane or pentobarbitone, drugs known to decrease cortical output of ACh, 4AP (i.v. or i.p.) elicited a significant increase in the output of ACh. The time‐courses of the 4AP‐induced effects were different depending on the anaesthetic drug used: an immediate increase slowly fading in urethane anaesthesia and a gradual increase after delayed onset in pentobarbitone‐anaesthetized rats.
In some urethane‐anaesthetized rats, respiratory frequency was kept constant (tracheotomy, connection to respirator, bilateral vagotomy) and prazosin (1 mg/kg i.v.) was administered to reduce the 4AP‐induced increase of blood pressure. Cortical output of ACh was not related to changes in blood pressure. Moreover, the 4AP‐induced increase in cortical ACh output was not related to changes in respiratory frequency.
In summary systemic administration of 4AP in subconvulsive doses (1 and 3 mg/kg) increased cortical output of ACh in rats anaesthetized with urethane or pentobarbitone or after injection of morphine, but not in untreated freely moving rats. It is suggested that the anaesthetic agents and morphine may cause an imbalance between excitatory and inhibitory central pathways, and that this imbalance may play a role in their depressant effect on cortical output of ACh and/or in the 4AP‐induced facilitation described in this paper.
EFFECTS OF RITODRINE, A β2‐ADRENOCEPTOR AGONIST, ON SMOOTH MUSCLE CELLS OF THE MYOMETRIUM OF PREGNANT RATS
Authors: IZUMI HIDETAKA , KISHIKAWA TADAO 
Published: July 2012

Effects of ritodrine on the electrical and mechanical activities of the myometrium of pregnant rats were investigated in relation to cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) production and the actions of isoprenaline.
In the longitudinal muscle cells of the 22nd day of gestation, ritodrine (> 10−8 m) hyperpolarized the membrane, reduced the membrane resistance and suppressed the amplitude of contraction. Increased concentrations of ritodrine (> 10−7 m) suppressed the generation of spikes and increased the amount of cyclic AMP produced. These actions of ritodrine were much the same as those of isoprenaline but the dose‐response curves of all parameters were shifted to the right.
The effects of ritodrine on the circular muscle cells at the 22nd day of gestation were similar to those observed in the longitudinal muscle cells.
In the circular muscle cells at the 17–19th days of gestation, ritodrine produced neither a hyperpolarization nor an increase in cyclic AMP production (up to 10−5m) but did reduce the plateau potential and did relax the tissue (> 10−7 m).
In the longitudinal muscle cells, during the 17–19th days of gestation, the responses of the tissues were similar to those observed in circular muscles on the 22nd day of gestation. These actions of ritodrine were suppressed by propranolol (10−6 m).
These results indicate that ritodrine is a β‐adrenoceptor agonist and its mechanism of action similar to that of isoprenaline. However, the potency of ritodrine was approximately 100 times less than that of isoprenaline.
RELATIONSHIP BETWEEN TYRAMINE POTENTIATION AND SELECTIVE INHIBITION OF MONOAMINE OXIDASE TYPES A AND B IN THE RAT VAS DEFERENS
Authors: FINBERG J.P.M. , TENNE M. 
Published: July 2012

The degree of selective monoamine oxidase (MAO) inhibition produced by (−)‐(deprenyl, clorgyline, LY51641 and tranylcypromine was examined in relation to modification of tyramine and noradrenaline contractile responses of the rat isolated vas deferens.
All inhibitors possessed reversible α‐adrenoceptor blocking activity, determined against noradrenaline on the denervated vas deferens. For LY51641 and tranylcypromine, antagonism was competitive, with pA2 values of 6.17 and 5.26.
Clorgyline, LY51641 and (−)‐deprenyl (10−5m) inhibited the tyramine response while present in the organ bath: LY51641, which was the most potent as an α‐adrenoceptor blocker, produced this effect at 10−6m. Responses to tyramine and noradrenaline were potentiated on washing out the inhibitors, but noradrenaline potentiation was seen only when tyramine had been present in the system.
Tranylcypromine (10−6m) potentiated responses to noradrenaline and tyramine while present in the organ bath.
Potentiation of tyramine responses by clorgyline and LY51641 occurred at 91% and 64% inhibition of MAO type A respectively, although full potentiation of the tyramine response was elicited only when substantial inhibition of both enzyme types occurred. Selective inhibition of MAO type B by 67% (with deprenyl) was not associated with tyramine potentiation.
CONTRIBUTION OF PROSTAGLANDINS AND THROMBOXANES TO THE ADENOSINE AND ATP‐INDUCED CONTRACTION OF GUINEA‐PIG ISOLATED TRACHEA
Authors: ADVENIER C. , BIDET D. , FLOCH‐SAINT‐AUBIN A. , RENIER A. 
Published: July 2012

In in vitro experiments adenosine 5′‐triphosphate (ATP) and adenosine were found to exert different effects on the guinea‐pig isolated trachea depending on whether the trachea had previously been contracted with acetylcholine (ACh) (6.6 × 10−6 m) or was at resting tone.
ATP and adenosine (10−5 and 10−3 m) were equipotent in relaxing the precontracted guinea‐pig trachea, since concentrations of 1.09 ± 0.35 and 0.39 ± 0.16 mm respectively reduced by 25% the ACh‐induced contraction.
ATP and adenosine (10−5 and 10−4 m) caused a moderate contraction of the guinea‐pig trachea under resting tone. This effect was antagonized by inhibitors of cyclo‐oxygenase (indomethacin 10−6m, aspirin 0.3 × 10−3m and 3 × 10−3m) and of thromboxane synthetase (nictindole 10−7m, imidazole 5 × 10−5 m), which suggests an indirect mechanism of action with release of arachidonic acid derivatives.
EVIDENCE FOR THE CARRIAGE OF SILVER BY SULPHADIMIDINE: INHIBITION OF PROTEOLYTIC ENZYMES
Authors: BALLINGER P.M. , GRIFFIN M.M. , ITZHAKI S. , STEVEN F.S. 
Published: July 2012

Trypsin in free solution and trypsin‐sepharose were shown to be inhibited by Ag+ in the absence of Cl‐.
In the presence of Cl‐ and absence of a suitable carrier, Ag+ has no inhibitory action on trypsin or chymotrypsin.
Sulphadimidine bound Ag+ in the presence of Cl‐, and carried the Ag+ to both trypsin and chymotrypsin in free solution as well as to trypsin‐sepharose leading to the inhibition of all these enzyme systems.
The neutral protease of tumour cell surfaces was inhibited by Ag+ transported by sulphadimidine in the presence of Cl‐.
Kinetic data demonstrated the requirements for both Ag+ and carrier to effect inhibition, the degree of inhibition being directly related to the molarity of each of these reagents.
The known inhibition of trypsin by Ag+ binding to histidine in the active site has been defined in mechanistic terms employing the sulphonamide drug, sulphadimidine, to illustrate this exchange mechanism.
PRESYNAPTIC γ‐AMINOBUTYRIC ACID RECEPTORS IN THE RAT ANOCOCCYGEUS MUSCLE AND THEIR ANTAGONISM BY 5‐AMINOVALERIC ACID
Authors: MUHYADDIN M. , ROBERTS P.J. , WOODRUFF G.N. 
Published: July 2012

The effects of γ‐aminobutyric acid (GABA) and related drugs on the isolated anococcygeus muscle of the rat were determined.
GABA caused a dose‐related inhibition of the electrically‐evoked twitch response.
The maximum response to GABA was a 56.8% depression of twitch response, with an EC50 of 0.68 μm.
(±)‐Baclofen mimicked the effect of GABA (EC50 0.9 μm). (+)‐Baclofen was more than 100 times less active than (−)‐baclofen.
The response to GABA was unaffected by picrotoxin or bicuculline but was antagonized by 5‐aminovaleric acid (0.5 mm).
Our results suggest that GABAB receptors are present on motor nerve terminals in the rat anococcygeus muscle and that 5‐aminovaleric acid is an antagonist of these receptors.
PHARMACOLOGICAL EVIDENCE FOR THE SUBCLASSIFICATION OF CENTRAL DOPAMINE RECEPTORS IN THE RAT
Authors: GOWER ALMA J. , MARRIOTT A.S. 
Published: July 2012

The relative potencies of dopamine receptor agonists in causing stereotypy in rats when injected into the olfactory tubercles, and contralateral rotation when injected unilaterally into the caudate nucleus of rats with lesions of the nigro‐striatal dopamine pathway, were determined. The actions of some agonists in eliciting these responses following peripheral injection, and the relative potencies of dopamine receptor antagonists in inhibiting them were also determined.
Dopamine, apomorphine and 2‐amino‐5, 6 and 2‐amino‐6, 7‐dihydroxy‐1,2,3,4‐tetrahydronaphthalene (A‐5, 6 DTN, A‐6, 7 DTN) and N,N dipropyl A‐5, 6DTN induced both responses. In contrast, 2,3,4,5‐tetrahydro‐7,8‐dihydroxy‐1‐phenyl‐1H‐3‐benzazepine HCl (SK & F 38393) whether injected intracerebrally or peripherally, induced contralateral rotation but not stereotypy.
Contralateral rotation and stereotypy induced by apomorphine or N,N dipropyl A‐5, 6 DTN were inhibited by haloperidol, pimozide and fluphenazine but these drugs failed to inhibit rotation induced by SK & F 38393. Clozapine inhibited rotation induced by SK & F 38393, apomorphine or N,N dipropyl A‐5, 6 DTN but failed to inhibit stereotypy. Loxapine was more potent in inhibiting stereotypy than rotation, whereas clothiapine inhibited rotation and stereotypy at similar doses irrespective of the agonist used to elicit the response.
Contralateral rotation induced by SK & F 38393 was not inhibited by yohimbine, prazosin, atropine, methysergide, mepyramine or propranolol.
The results provide evidence that contralateral rotation induced by dopamine receptor agonists is mediated by two different classes of dopamine receptors and that these receptors differ from those mediating the stereotypy response.
The receptors mediating these responses appear classifiable in terms of their sensitivity to the agonist actions of SK & F 38393 or apomorphine respectively. SK & F 38393‐sensitive receptors are susceptible to blockade by clozapine but are not blocked by haloperidol, pimozide or fluphenazine. Apomorphine‐sensitive receptors are susceptible to blockade by haloperidol, pimozide and fluphenazine but appear divisible into two sub‐classes depending on whether or not they are blocked by clozapine and on their sensitivity to blockade by loxapine.
Antinociceptive actions of morphine and buprenorphine given intrathecally in the conscious rat
Authors: Bryant Rosamunde M. , Olley Jean E. , Tyers M.B. 
Published: July 2012

The antinociceptive effects of morphine and buprenorphine given intrathecally and subcutaneously have been compared in the conscious rat.
In the paw pressure test, when given subcutaneously buprenorphine 0.001–0.1 mg/kg s.c., was approximately 100 times more potent than morphine 0.1–3 mg/kg s.c., but in the hot plate test, buprenorphine 0.03–3.0 mg/kg s.c., produced a bell‐shaped dose‐response curve of low maximum effect and was about equipotent with morphine 0.03–3 mg/kg s.c.
When given intrathecally buprenorphine 10 μg and morphine, 10–60 μg, were approximately equipotent in both paw pressure and hot plate tests. Furthermore, morphine produced these effects at 1/25th of the minimum effective parenteral dose while the dose of buprenorphine exceeded the parenteral dose.
It is concluded that the predominant site of the analgesic action of buprenorphine is supraspinal. The significance of these findings in relation to the role of spinal opiate receptors is discussed.
Inhibition of cardiac sympathetic neurotransmission by histamine in the dog is mediated by H1‐receptors
Authors: Kimura T. , Satoh S. 
Published: July 2012

The role of histamine H1‐ and H2‐receptors in mediating prejunctional inhibition of cardiac sympathetic neurotransmission and histamine‐induced coronary vasodilatation were investigated in perfused dog hearts in situ.
Intra‐arterial injections of histamine into the right coronary artery during the resting state caused slightly positive chronotropic responses in doses larger than 1 μg.
Histamine in doses of 0.1 to 10 μg into the right coronary artery reduced the tachycardia resulting from electrical stimulation of the cardiac sympathetic nerves.
Intra‐coronary infusions of chlorpheniramine (300 μg/min) significantly reduced the histamine‐induced depression of cardiac nerve stimulation. The effects of cimetidine (300 μg/min) and metiamide (300 μg/min) were less pronounced.
Histamine (1 to 10 μg) further increased heart rate resulting from the continuous intra‐coronary infusion of noradrenaline (1 or 3 μg/min).
Intra‐arterial injections of histamine (0.1 to 10 μg) caused an increase in coronary blood flow in a dose‐dependent manner. This was partially inhibited by intra‐coronary infusion of chlorpheniramine (10 to 300 μg/min) and by cimetidine (10 to 300 μg/min). The combination of both drugs (10 to 100 μg/min of each) caused a larger inhibition.
The present results suggest that the histamine‐induced depression of heart rate during cardiac sympathetic nerve stimulation is due to a prejunctional effect mediated mainly by H1‐receptors. Histamine‐induced coronary vasodilatation in the dog is mediated both by H1‐ and H2‐receptors.
Studies on the interaction between cerebral 5‐hydroxytryptamine and γ‐aminobutyric acid in the mode of action of diazepam in the rat
Authors: Collinge J. , Pycock C.J. , Taberner P.V. 
Published: July 2012

The effect of the benzodiazepine, diazepam, administered for 7 days in doses between 1.25 and 5 mg kg−1 was studied on the turnover of 5‐hydroxytryptamine (5‐HT) in rat cerebral cortex. 5‐HT turnover was assessed by calculating the ratio of the concentration of the major metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) to that of 5‐HT (i.e., 5‐HIAA:5‐HT). Diazepam (2.5 and 5 mg kg−1 i.p. daily for 7 days) significantly reduced cerebral cortical 5‐HT turnover.
The effect of manipulating cerebral γ‐aminobutyric acid (GABA) mechanisms on this action of diazepam was studied. Treatment of animals with a subconvulsive dose of Picrotoxin (3 mg kg−1 i.p.) reversed the fall in cortical 5‐HT turnover seen following diazepam. In contrast, however, treatment with the GABA transaminase inhibitors, amino‐oxyacetic acid (25 mg kg−1) or ethanolamine‐O‐sulphate (250 mg kg−1, 7 days) which elevated cerebral GABA concentrations, enhanced the reduction in cortical 5‐HT turnover following diazepam.
Focal injection of picrotoxin (0.1 μg) into the region of the dorsal raphé nucleus reversed the decrease in cortical 5‐HT turnover caused by diazepam.
The hypothesis that doses of diazepam which result in total plasma concentrations comparable to those observed in man produce a reduction in 5‐HT turnover mediated via GABA neurones is discussed.
Interactions of γ‐aminobutyric acid and noradrenaline in the high pressure neurological syndrome
Authors: Angel A. , Halsey M.J. , Wardley‐Smith Bridget 
Published: July 2012

The effects on the high pressure neurological syndrome (HPNS) of reducing brain noradrenaline (NA) levels were studied in adult rats. The onset of tremors and convulsions, which occur as pressure is increased, were used as endpoints for assessing the onset and severity of the HPNS.
Neonatal treatment with 6‐hydroxydopamine (6‐OHDA; 100 mg kg−1 i.p. alternate days from birth for 2 weeks) which depleted brain NA, produced no change in the HPNS as assessed by the appearance of tremors and convulsions.
A second series of NA‐depleted rats and equivalent controls were treated with a GABA agonist, muscimol, 0.1 μg intracerebroventricularly. Subsequently the rats were exposed to pressure and the onset and severity of the HPNS was assessed by observation of tremors and convulsions. A combination of NA depletion and intracerebroventricular injection of muscimol significantly raised the onset pressures for tremors and convulsions, i.e. delayed the appearance of the HPNS.
These results are consistent with the HPNS being associated with a disturbance in the balance of two or more neurotransmitter systems, rather than simply an increase or reduction in levels of a single transmitter.
Conversion of sodium channels to a form sensitive to cyclic AMP by component(s) from red cells
Authors: Cuthbert A.W. , Spayne J. A. 
Published: July 2012

Sodium transport has been measured in the isolated epithelium from colons of male Sprague‐Dawley rats.
Sodium transport in colons was induced by pretreating the animals with dexamethasone (6 mg kg−1) which caused the appearance of an amiloride‐sensitive short circuit current within a few hours.
Forskolin, a diterpene, which activates adenylate cyclase, was found to increase the cyclic adenosine monophosphate (cyclic AMP) content of rat colons and also to increase short circuit current at the same time. However, measurements of chloride and sodium fluxes across the epithelium indicated that forskolin activates chloride secretion but has no effect on sodium transport.
In confirmation of (3) it was found that the amiloride‐sensitive short circuit current was unchanged after the short circuit current had been increased by forskolin under a variety of conditions.
The behaviour of the mammalian colon as indicated in (3) and (4) is unlike that of amphibian sodium transporting epithelia. It is shown that in toad urinary bladder forskolin increases amiloride‐sensitive short circuit current.
Procedures were investigated which might make sodium transport in the mammalian colon sensitive to cyclic AMP. Exposing the apical surface to sonicated suspensions of nucleated red cells (frog, toad and duck), followed by washing, gave preparations with amiloride‐sensitive short circuit currents which were increased by forskolin or dibutyryl cyclic AMP.
It would appear that the sodium channel in the mammalian colon, unlike that of amphibian tissues, has lost the ability to have its properties modified by cyclic AMP. Incubation of colons with sonicated suspensions of nucleated red cells apparently modifies the tissues such that sodium transport across the tissue becomes sensitive to the nucleotide.