bluuebunny/crossref_metadata_2025_split huggingface dataset:
SEPARATE 5‐HYDROXYTRYPTAMINE RECEPTORS ON THE SALIVARY GLAND OF THE BLOWFLY ARE LINKED TO THE GENERATION OF EITHER CYCLIC ADENOSINE 3‘,5’‐MONOPHOSPHATE OR CALCIUM SIGNALS
Authors: BERRIDGE MICHAEL J. , HESLOP JOHN P. 
Published: July 2012

5 ‐Hydroxytryptamine (5 ‐HT) stimulates the formation of two separate second messengers in the salivary gland of the blowfly. Activation of adenylate cyclase raises cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) whereas the hydrolysis of phosphatidylinositol (PI) is associated with an increase in calcium permeability. The possibility that these two signal pathways might be controlled by separate 5‐HT receptors was studied by testing the specificity of 5‐HT analogues and antagonists.
The parent compound 5‐HT was found to stimulate both cyclic AMP formation and the related parameters of PI hydrolysis and calcium transport with similar dose‐response relationships.
Certain analogues such as 4‐ and 5‐fluoro‐α‐methyltryptamine were capable of raising cyclic AMP levels and stimulating fluid secretion but did not stimulate the hydrolysis of PI or the entry of calcium.
Other analogues, which had chloro or methyl substituents at the 5‐position, were found to stimulate the hydrolysis of PI and the transport of calcium at much lower doses than those required to stimulate the formation of cyclic AMP.
Antagonists were also found to exert selective effects. Methysergide was a potent inhibitor of PI hydrolysis whereas cinanserin was far more selective in blocking the stimulatory effect of 5‐HT on cyclic AMP formation.
It is concluded that 5‐HT acts on two separate receptors, a 5‐HT1 receptor acting through calcium and a 5‐HT2 receptor which mediates its effects through cyclic AMP.
DISTINCTION BETWEEN THE EFFECTS OF BARBITURATES, BENZODIAZEPINES AND PHENYTOIN ON RESPONSES TO γ‐AMINOBUTYRIC ACID RECEPTOR ACTIVATION AND ANTAGONISM BY BICUCULLINE AND PICROTOXIN
Authors: SIMMONDS M.A. 
Published: July 2012

Interactions of depressant and anticonvulsant drugs with the neuronal γ‐aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism.
Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol.
Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone.
The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties.
VASCULAR AND SENSORY RESPONSES OF HUMAN SKIN TO MILD INJURY AFTER TOPICAL TREATMENT WITH CAPSAICIN
Authors: CARPENTER SANDRA E. , LYNN BRUCE 
Published: July 2012

Immediately after several topical applications of capsaicin at 2‐hourly intervals, human forearm skin would no longer develop flare (vasodilatation) around a small injury. At the same time heat pain thresholds were reduced on average by 3.5°C. These results are consistent with block by capsaicin of the effector side of the axon reflex, perhaps by depleting nerve terminals of substance P.
Over a period from several days to several weeks after treatment, flare was diminished and heat pain thresholds were slightly elevated. These changes may be due to long‐lasting damage of cutaneous nerve terminals by capsaicin.
THE EFFECTS OF 4‐AMINOPYRIDINE ON THE ISOLATED VAS DEFERENS AND ITS EFFECTS ON THE INHIBITORY PROPERTIES OF ADENOSINE, MORPHINE, NORADRENALINE AND γ‐AMINOBUTYRIC ACID
Authors: STONE T.W. 
Published: July 2012

Adenosine, adenosine 5′‐triphosphate (ATP), morphine, noradrenaline, γ‐aminobutyric acid (GABA) phentolamine and amyl nitrite were used to inhibit electrically‐evoked contractions of the isolated superfused vas deferens of the mouse.
The inhibitory effects of adenosine ATP, morphine, noradrenaline and GABA, which are thought to be due to presynaptic action, were reduced by perfusion with media containing 4‐aminopyridine (4AP) or tetraethylaminonium (TEA) ions. The inhibitory effects of phentolamine and amyl nitrite were unaffected by 4AP or TEA.
Quinidine, which like 4AP and TEA produced some increase of twitch height, did not reduce responses to the various agonists, indicating that an increased muscle contraction was not itself responsible for the reduced responses.
It is concluded that antagonism between 4AP and adenosine is not a specific interaction, as had been suggested, but probably reflects an interaction with Ca2+ requiring processes in the presynaptic terminal.
EFFECTS OF CAFFEINE, THEOPHYLLINE AND THEOBROMINE ON SCHEDULED CONTROLLED RESPONDING IN RATS
Authors: CARNEY JOHN M. 
Published: July 2012

Rats were trained to respond under a variable interval 30 s (VI 30) schedule of food reinforcement.
Caffeine (0.32–32 mg/kg), theophylline (1.0–56 mg/kg) and theobromine (10–320 mg/kg) in general produced dose‐related decreases in operant responding. At relatively low doses, caffeine (1.0 mg/kg) and theophylline (3.2 mg/kg) produced slight but nonsignificant increases in VI 30 responding.
The rank order of potency for producing decreases in responding was caffeine > theophylline > theobromine.
Daily caffeine injections (32 mg/kg, i.p.) resulted in the development of caffeine tolerance. This tolerance was characterized by a 6 fold shift to the right in the caffeine dose‐effect curve Saline substitution for the 32.0 mg/kg caffeine maintenance dose resulted in a substantial decrease in responding.
PRODUCTION OF TOLERANCE AND PHYSICAL DEPENDENCE IN THE RAT BY SIMPLE ADMINISTRATION OF MORPHINE IN DRINKING WATER
Authors: BADAWY A.A.‐B. , EVANS C.M. , EVANS M. 
Published: July 2012

Rats are capable of consuming solutions of morphine sulphate in drinking water ad libitum in the absence of taste‐masking chemicals and without the need for scheduled provision or prior parenteral administration of the drug.
The success of this method depends on the initial provision of a 0.1 mg/ml solution of morphine sulphate.
When the drug concentration is increased to 0.4 mg/ml, the rats achieve an average daily intake of 50 mg/kg body wt. each.
Daily intake of morphine may be increased by at least about three fold by increasing the drug concentration to 1.2 mg/ml.
Oral morphine administration causes only a moderate loss in body weight.
Rats whose daily intake of the drug is 50 mg/kg exhibit tolerance to the analgesic action of morphine and show a drastic loss in body weight at 24 h after withdrawal and most of the behavioural symptoms of the naloxone‐precipitated withdrawal syndrome.
It is suggested that this simple method of morphine administration is suitable for further biochemical and behavioural studies of the actions of the drug.
THE EFFECTS OF PRAZOSIN, PHENTOLAMINE AND PHENOXYBENZAMINE ON INHIBITORY α‐ADRENOCEPTORS IN THE GUINEA‐PIG ISOLATED ILEUM
Authors: FAGBEMI S.O. , SALAKO L.A. 
Published: July 2012

The relaxant effect of noradrenaline on strips of guinea‐pig isolated terminal ileum was blocked by pretreatement with prazosin, phentolamine, yohimbine and phenoxybenzamine.
The presence of a very high concentration of noradrenaline (50 μm) during exposure to the blocking agent protected against the blocking effect of the drugs.
Yohimbine, prazosin and phentolamine partially protected against irreversible blockade by phenoxybenzamine.
Spontaneous release of acetylcholine in the unstimulated ileum was blocked by noradrenaline (0.059–5.9 μm). This effect of noradrenaline was antagonized by phentolamine (0.13–2.6 μm) and yohimbine (0.051–0.51 μm) but not by prazosin (0.53–5.3 μm) or phenoxybenzamine (4.2–42 μm). All four antagonists reversed the noradrenaline‐induced relaxation of the ileum.
Acetylcholine output in the transmurally stimulated ileum was inhibited by noradrenaline. This effect of noradrenaline was antagonized by phentolamine and yohimbine but not by prazosin or phenoxybenzamine. The first two antagonists blocked the noradrenaline‐induced inhibition of evoked twitches of the ileum while the last two had no effect.
The results show (a) that prazosin has no effect on presynaptic α‐adrenoceptors located on cholinergic nerve endings in the guinea‐pig ileum and (b) that prazosin, phentolamine and phenoxybenzamine act on the same subgroup of postsynaptic α‐adrenoceptors on the smooth muscle of the guinea‐pig ileum.
THE EFFECTS OF SUBSTANCE P ON SMOOTH MUSCLE CELLS AND ON NEURO‐EFFECTOR TRANSMISSION IN THE GUINEA‐PIG ILEUM
Authors: FUJISAWA KAZUAKI , ITO YUSHI 
Published: July 2012

The effects of substance P (SP) on the membrane and contractile properties of the smooth muscle cell, or on neuro‐effector transmission in the guinea‐pig ileum were observed by means of microelectrodes, double sucrose gap and tension recording.
SP (10−13‐10−10 M) induced a phasic contraction of longitudinal muscle strips, but did not change the muscle tone of circular muscle strips, in concentrations up to 10−8 M.
SP (1010‐10‐8M) evoked three different membrane responses in longitudinal muscle cells: (i) bursts of spike discharges with no significant change in the membrane potential and input membrane resistance; (ii) bursts of spike discharges with a small but clear depolarization of the membrane and increase in the input membrane resistance; (iii) slow waves with no change in the membrane potential.
In the circular muscle cells, low concentrations of SP (< 10−8M) did not affect the membrane potential or the spikes, but SP (10−7M) increased the spike discharges with no significant change in the membrane potential.
SP (10−10M) reduced the threshold depolarization required for the generation of action potentials with no change in membrane potential of the longitudinal muscle cells.
Pretreatment with atropine (5 × 10−6M), tetrodotoxin (TTX 10−6M) or baclofen (4.7 × 10−6M) had no effect on the excitatory actions of SP on the smooth muscle cells of longitudinal and circular muscle strips.
Excitatory actions of SP on the membrane potential or spike activities of longitudinal muscle cells were preserved in NaCl but not in Ca‐deficient solution.
SP (10−10‐10−9M) enhanced the amplitude of the excitatory junction potentials (e.j.ps) evoked by electrical field stimulation in longitudinal muscle cells with no change in the membrane potential and input resistance. SP (10−10‐10−9M), however, did not change the amplitude of inhibitory junction potentials (i.j.ps) recorded from the circular muscle cells.
These results indicate that SP in relatively low concentrations acts on both smooth muscle cells and on excitatory neuro‐effector transmission in the longitudinal muscle; the main site of the action of SP is probably the muscle membrane.
PROTECTIVE EFFECTS OF GLUCAGON DURING THE ANAPHYLACTIC RESPONSE IN GUINEA‐PIG ISOLATED HEART
Authors: ANDJELKOVIC IVAN , ZLOKOVIC BERISLAV 
Published: July 2012

Cardiac anaphylaxis and the effects of glucagon pretreatment were studied in guinea‐pig isolated hearts actively sensitized to ovalbumin.
Antigen challenge of the sensitized hearts markedly increased creatine Phosphokinase (CPK) activity in the coronary venous effluent. Control values of CPK release from the hearts before challenge were 3.56 ± 0.15 mu min−1 mg−1. In the first 10 min following challenge, CPK release remained stable at increased levels which ranged between 4.88 ± 0.20 to 5.39 ± 0.38 mu min−1 mg−1. There was no correlation between immunologically released histamine and CPK release.
Pretreatment of the hearts with glucagon (0.15 μmol l−1) exerted a pronounced anti‐arrhythmic activity, reducing the conduction arrhythmias and completely preventing automaticity arrhythmias which normally occurred following ovalbumin challenge.
Anaphylactic histamine release was reduced significantly in the presence of glucagon. The percentage inhibition of histamine release from glucagon pretreated hearts, during the first 10 min after challenge, ranged between 58% and 94% of that from hearts similarly challenged in the absence of glucagon.
Glucagon significantly elevated sinoatrial nodal automaticity, enhanced atrioventricular conduction, improved coronary flow and reduced contractile force during anaphylaxis. It appears that these effects are caused both by modulating anaphylactic histamine release and by influencing the effects of the released histamine.
CPK release from the anaphylactic hearts was significantly inhibited in the presence of glucagon. The average percentage inhibition of CPK activity during the first 10 min after challenge ranged between 42% and 98%.
The findings from this study provide experimental evidence for protective effects of glucagon pretreatment during cardiac anaphylaxis.
EFFECT OF TMB‐8 ON THE PULMONARY VASOCONSTRICTOR ACTION OF PROSTAGLANDIN F2α AND THE THROMBOXANE MIMIC, U46619
Authors: ANGERIO ALLAN D. , FITZPATRICK THOMAS M. , KOT PETER A. , RAMWELL PETER W. , ROSE JOHN C. , SANTOIAN EDWARD C. 
Published: July 2012

TMB‐8 (8–(N,N‐diethylamino)octyl‐3, 4, 5 trimethoxybenzoate HCl), an intracellular calcium antagonist, had no direct action on the pulmonary vasculature of the perfused canine lung lobe preparation.
The pulmonary pressor response to the thromboxane mimic, U46619, was not affected by TMB‐8.
The vasopressor response to prostaglandin F2α (PGF2α>) was significantly attenuated but not completely blocked by TMB‐8.
We conclude that the pulmonary pressor response to PGF2α is dependent on both intracellular and extracellular calcium pools for contraction and that U46619 facilitates either solely extracellular calcium influx or mobilizes an intracellular calcium pool not inhibited by TMB‐8.
ELIMINATION OF GLYCERYL TRINITRATE: EFFECTS OF SEX, AGE, SPECIES AND ROUTE OF ADMINISTRATION
Authors: IOANNIDES C. , PARKE D.V. , TAYLOR I.W. 
Published: July 2012

Orally administered glyceryl trinitrate to rats undergoes extensive first pass metabolism leading to low bioavailability.
Sex differences in the plasma elimination of glyceryl trinitrate were seen in the rat, the female exhibiting the longer plasma half‐life. No sex differences in this respect were detected in the rabbit.
The plasma half‐life of glyceryl trinitrate was longer and the volume of distribution larger, in older animals.
The plasma elimination of glyceryl trinitrate was different in various animal species. There was a good correlation between plasma half‐life and animal bodyweight.
DESENSITIZATION OF PROSTACYCLIN RECEPTORS IN A NEURONAL HYBRID CELL LINE
Authors: BLAIR I.A. , LEIGH P.J. , MacDERMOT J. 
Published: July 2012

Prostacyclin and its stable analogue, carbacyclin, bind competitively to a single population of receptors, and activate adenylate cyclase of the NCB‐20 neuronal somatic cell hybrid (Kact = 40.1 nM and 96.1 nM respectively).
Culture of NCB‐20 cells in the presence of 1 μm carbacyclin for 4 to 16 h results in a progressive decrease in the prostacyclin‐dependent activation of adenylate cyclase in cell homogenates with an increase at 16 h of the Kact from 64.1 nm to 174.0 nm and decrease in the maximum adenylate cyclase activation from 41.2 to 15.1 pmol cyclic AMP min−1 mg−1 protein.
The prediction that the apparent decrease in affinity in the prostacyclin‐dependent activation of adenylate cyclase was secondary to a reduction in receptor numbers was tested directly by measuring binding of [3H]‐prostacyclin to membranes of cells exposed to carbacyclin for 16 h. This showed an actual decrease in affinity of the prostacyclin‐receptor interaction, as well as a decrease in the total receptor numbers. Thus prolonged exposure of NCB‐20 cells to carbacyclin caused reductions in both receptor numbers and affinity, reflected by measurements both of binding and adenylate cyclase activation.
EVIDENCE FOR CARRIAGE OF SILVER BY SULPHADIMIDINE: HAEMOLYSIS OF HUMAN ERYTHROCYTES
Authors: BALLINGER P.M. , BROWN B.S. , GRIFFIN M.M. , STEVEN F.S. 
Published: July 2012

Human erythrocytes suspended in isotonic saline haemolyse in the presence of both Ag+ ions and sulphadimidine.
Neither Ag+ ions nor sulphadimidine on their own will haemolyse erythrocytes suspended in isotonic saline.
At constant Ag+ ion concentration the degree of haemolysis of saline‐suspended erythrocytes depends upon the concentration of sulphadimidine.
Human erythrocytes suspended in isotonic sucrose (chloride‐free) haemolyse in the presence of Ag+ ions.
Sulphadimidine in chloride‐free sucrose competes with erythrocytes for Ag+ ions resulting in stoichiometric protection of the erythrocytes from the haemolytic action of Ag+ ions.
Haemolysis occurs when each erythrocyte receives approximately 1.2 × 109 Ag+ ions whether suspended in saline or sucrose.
Sulphadimidine acts as a carrier for Ag+ ions and so prevents their precipitation as AgCl when erythrocytes are suspended in saline.
RECEPTOR INTERACTIONS OF IMIDAZOLINES: α‐ADRENOCEPTORS OF RAT AND RABBIT AORTAE DIFFERENTIATED BY RELATIVE POTENCIES, AFFINITIES AND EFFICACIES OF IMIDAZOLINE AGONISTS
Authors: RUFFOLO ROBERT R. , WADDELL JAMES E. 
Published: July 2012

Noradrenaline and a series of imidazolines were used to characterize and differentiate the postsynaptic α‐adrenoceptors of rat and rabbit aortae.
Dose‐response curves in each tissue revealed marked differences in the profile of agonist activity among the compounds. Based on the ED50 values for each compound, a rank order of potency of oxymetazoline > noradrenaline > tramazoline > tetrahydrozoline > clonidine was obtained in rabbit aorta and an order of noradrenaline > clonidine > tramazoline > oxymetazoline was obtained in rat aorta. Tetrahydrozoline had no agonist activity in rat aorta.
Dissociation constants were determined for each agonist in rat and rabbit aortae. Again, differences between the tissues were observed to the extent that the rank order of affinities for the imidazolines were exactly opposite for the two tissues. In rabbit aorta the order was, oxymetazoline > tramazoline > tetrahydrozoline > clonidine, whereas in rat aorta it was, clonidine > tetrahydrozoline > tramazoline > oxymetazoline. The extremes in tissue selectivity were observed with clonidine, which had approximately 125 fold higher affinity in rat aorta, and oxymetazoline, which had approximately 4 times higher affinity in rabbit aorta.
The absolute values of relative efficacies of the imidazolines studied, and their rank order, also differed between the two tissues. The relative efficacies of oxymetazoline and tramazoline were more than 15 fold greater in rabbit aorta than in rat aorta. Furthermore, tetrahydrozoline had a greater relative efficacy than clonidine in rabbit aorta while the converse was true in rat aorta.
Differences in the rank order of potency, affinity and relative efficacy of noradrenaline and a series of imidazolines in rat and rabbit aortae indicate that the postsynaptic α‐adrenoceptors in these tissues are different. While the postsynaptic α‐adrenoceptor of rabbit aorta is clearly of the α1‐subtype, the exact nature of the postsynaptic α‐receptor of rat aorta is not clear. The unique α‐receptor of rat aorta has properties of both α1‐ and α2‐adrenoceptors.
The influence of substance P on the response of guinea‐pig isolated ileum to periarterial nerve stimulation
Authors: Grbović Leposava , Radmanoviě B.Ž. 
Published: July 2012

The effects of substance P (SP) on the responses of the guinea‐pig isolated ileum to periarterial nerve stimulation were studied. Electrical stimulation (2–50 Hz) of mesenteric periarterial nerves resulted in contraction of preparations pre treated with guanethidine. The responses were abolished by atropine and morphine, but unaffected by hexamethonium.
SP in a high concentration (0.65 μmol) inhibited reversibly, by about 40%, the responses of the guinea‐pig isolated ileum to periarterial nerve stimulation.
SP in a very low concentration (0.18 pmol) potentiated (by about 20%) the responses of the guinea‐pig isolated ileum to periarterial nerve stimulation.
In the presence of low concentrations (0.06–0.32 pmol) of SP, morphine (2.65 μmol) produced less inhibition of the responses to periarterial nerve stimulation, and recovery from morphine inhibition of contraction was accelerated.
These results indicate that SP may act as a modulator on prejunctional acetylcholine release in the guinea‐pig ileum.
Pharmacological characterization of the opioid receptor in the submucous plexus of the guinea‐pig oesophagus
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: July 2012

The cholinergically mediated electrically‐induced contractions of the submucous plexus‐longitudinal muscularis mucosae preparation of the guinea‐pig oesophagus were used to study the actions of opioid peptides and morphine.
The twitch contractions of the tissue (0.1 Hz, 0.5 ms, supramaximal voltage) were inhibited by all the opioid peptides and morphine in a concentration‐dependent manner. The order of potency was dynorphin‐(1–13) > α‐neo‐endorphin > β‐endorphin > [d‐Ala2]‐methionine‐enkephalin ≪≪ α‐endorphin, methionine‐enkephalin, leucine‐enkephalin and morphine.
The inhibitory actions of dynorphin‐(1–13) (20 nm), α‐neo‐endorphin (100 nm) and β‐endorphin (3 μm) were completely reversed either by naloxone (1 μm) or by morphine (100 μm). The Ke values of naloxone against dynorphin‐(1–13) and α‐neo‐endorphin were 30 and 25 nm, respectively.
Increasing the concentration of calcium from 1.8 to 3.6 mm in Tyrode solution decreased the sensitivity of the tissue to dynorphin‐(1–13) 7.4 times and to α‐neo‐endorphin 462 times.
The inhibitory actions of dynorphin‐(1–13) (100 nm) and α‐neo‐endorphin (300 nm) were inversely related to stimulus frequency, being most active at low frequencies (0.1–1 Hz), and least active at high (30 Hz).
Exogenously applied acetylcholine produced concentration‐dependent contractions of the isolated muscularis mucosae, with an EC50 of 72.6 ± 4.5 nm. The contractile response of the oesophagus to acetylcholine was not affected by the pretreatment of the tissue with dynorphin‐(1–13) (100 nm), α‐neo‐endorphin (300 nm) or β‐endorphin (3 μm).
It is concluded that the submucous plexus‐longitudinal muscularis mucosae of the guinea‐pig oesophagus is inhibited by opioid peptides acting at prejunctional opioid receptors, probably of the κ‐subtype.