bluuebunny/crossref_metadata_2025 huggingface dataset:
ANAPHYLACTIC CONTRACTION OF PULMONARY BLOOD VESSELS OF CHICKEN
Authors: CHAND N. , EYRE P.
Published: July 2012

Isolated pulmonary arterial and vein strips from sensitized or non‐sensitized chickens exhibited dose‐dependent contractions to adrenaline>, noradrenaline>, 5‐hydroxytryptamine>, histamine>, dopamine. Individual variability in the responsiveness of the vessels to agonists was marked. In general veins were 2 to 25 times more sensitive to agonists than arterial strips.

Isoprenaline (a relatively specific β‐adrenoceptor agonist) induced relaxations of the submaximally contracted pulmonary vein and arteries at low doses and contractions at high concentrations.

Contractile responses to acetylcholine or carbachol were not regularly recorded; only 50% of the vessels reacted to cholinoceptor agonists over a wide threshold dose range.

Chicken pulmonary vessels were found relatively insensitive to bradykinin.

Effects of prostaglandins were variable. Prostaglandin induced dose‐related contractions of the vein and arterial strips; prostaglandins E1 and E2 at low doses relaxed partially contracted pulmonary artery irrespective of the spasmogen used and further increase in doses induced either no effect or contractions. Prostaglandin E1 induced marked and rapid contractions of the vein. Prostaglandin E2 induced relaxations of the prostaglandin F2α‐contracted vein only, but produced no effect or slight contractions of the veins partially contracted to other spasmogens.

Pulmonary arterial and vein strips obtained from chickens sensitized to horse plasma exhibited Schultz‐Dale contractions of variable magnitude and duration to specific antigenic challenge only. In many vessels, antigen‐induced contractions were associated with marked increase in spontaneous activity.

The importance of the Schultz‐Dale reaction in avian pulmonary vessels is discussed in relation to the right heart dilatation associated with anaphylaxis in the chicken.
THE EFFECTS OF METIAMIDE ON CELL‐MEDIATED IMMUNE REACTIONS IN THE GUINEA‐PIG
Authors: DALE M. MAUREEN
Published: July 2012

1 The effects of the H2‐receptor antagonist, metiamide, on two types of cell‐mediated immune response in vivo was investigated in the guinea‐pig, in a test of the hypothesis that H2‐receptor antagonists would result in ‘runaway’ unregulated hypersensitivity reactions.

2 Metiamide in doses of 5 mg‐125 mg/kg given by 6‐hourly injection during sensitization and challenge did not modify the delayed hypersensitivity reaction to tuberculin.

3 Metiamide in doses of 25‐125 mg/kg given by injection, 6‐hourly throughout sensitization to dinitrofluorobenzene (DNFB) and subsequent challenge six days later, did not modify the contact sensitivity reaction to DNFB.

4 It is concluded that metiamide, given during these cell‐mediated immune reactions in the guinea‐pig, does not enhance cell‐mediated hypersensitivity responses.
EFFECTS OF N‐METHYLAMINO ACIDS AND CONVULSANTS ON SPONTANEOUS ACTION POTENTIALS IN GUINEA‐PIG CEREBELLAR SLICES
Authors: OKAMOTO K. , QUASTEL J.H.
Published: July 2012

N‐methyl‐γ‐aminobutyrate (N‐methylGABA), N‐methylglycine, N‐methyltaurine and N‐methylβ‐alanine diminished the frequency of spontaneous spike discharges in guinea‐pig cerebellar slices. Usually a weak excitatory effect preceded the inhibition.

The inhibitory effects of N‐methylGABA and N‐methylβ‐alanine were competitively antagonized by both picrotoxin and strychnine.

The inhibitory action of N‐methyltaurine was competitively suppressed by strychnine and by low concentrations of picrotoxin.

The inhibitory action of N‐methylglycine was suppressed by strychnine but not by picrotoxin. The suppression was competitive at low concentrations of strychnine.

N‐methyldl‐glutamate brought about a strong inhibition followed by a strong excitation of the neurones. The inhibitory effects were competitively suppressed by both picrotoxin and strychnine. Neither convulsant affected the excitation.

Whereas l‐ or D‐glutamate caused only excitation in the majority of cells examined, a small proportion of the cells exhibited inhibition preceding the excitation by l‐ or D‐glutamate. Such inhibitory effects were suppressed by picrotoxin but not by strychnine.

Kinetic analyses of the dose‐response curves for the N‐methylamino acid in the presence or absence of the convulsant indicated that the number of molecules of the amino acid combining with the receptor site to produce a response was 3 for N‐methylGABA, 2 for N‐methylglycine, 3 for N‐methyltaurine, 3 for N‐methylβ‐alanine. The corresponding value was 1 for N‐methyldl‐glutamate (inhibition). The number of molecules of convulsant combining with the receptor site was calculated to be 2 for picrotoxin with N‐methylGABA, N‐methylβ‐alanine and N‐methyldl‐glutamate and 1 for strychnine with all N‐methylamino acids examined.
THE FATE OF BIOGENIC MONOAMINES IN PERFUSED RABBIT LUNG
Authors: GILLIS C.N. , ROTH J.A.
Published: July 2012

Inactivation of β‐phenylethylamine and several of its derivatives was studied in a preparation of rabbit lung perfused with Krebs physiological medium at 37°C. Inactivation or removal of these compounds was calculated as the difference between the concentration of each amine in the perfusion medium and the effluent, collected separately from each lung. The extent of amine metabolic degradation was also measured, by column chromatography, in lung effluent.

With this technique the magnitude of amine removal as a function of concentration was determined and an apparent Km and Vmax of removal were calculated for each amine.

Percentage removal was highest with phenylethylamine (95%), and decreased, apparently in relation to increasing phenyl‐ and side chain‐hydroxylation (and therefore likely increased hydrophilicity), with 5‐hydroxytryptamine (64%), tyramine (53%), octopamine (35%), dopamine (32%) and noradrenaline (23%).

Inactivation of each amine could be accounted for by metabolic degradation to deaminated products, which appeared in lung effluent within 90 s of beginning amine perfusion.

When intrapulmonary metabolism of phenylethylamine was inhibited by simultaneous perfusion with semicarbazide (10 mM) and pargyline (10 μM), the removal rate was unaltered, establishing that uptake of the amine from the vascular space is not dependent on metabolism at least for 4 min infusions.
THE PHARMACOLOGY OF ADRENERGIC NEURONAL RESPONSES IN THE CEREBRAL CORTEX: EVIDENCE FOR EXCITATORY α‐ AND INHIBITORY β‐RECEPTORS
Authors: BEVAN P. , BRADSHAW C.M. , SZABADI E.
Published: July 2012

The technique of microelectrophoresis was used to compare the actions of a range of adrenoceptor agonists on single cortical neurones in the rat anaesthetized with halothane.

Phenylephrine and methoxamine were exclusively excitatory, whereas salbutamol was entirely depressant. Noradrenaline and isoprenaline could evoke both excitatory and depressant responses. Lower doses of isoprenaline usually evoked depressions, whereas higher doses, on the same cell, evoked excitatory responses.

The α‐adrenoceptor blocking agents, phentolamine and phenoxybenzamine, reversibly antagonized excitatory responses to adrenoceptor agonists, without affecting depressant responses to adrenoceptor agonists or excitatory responses to acetylcholine.

The β‐adrenoceptor blocking agents, propranolol and sotalol, reversibly antagonized both depressant and excitatory responses to adrenoceptor agonists, without affecting responses to acetylcholine. When the effect of sotalol on excitatory and depressant responses to adrenoceptor agonists was compared on the same cell, the depressant responses could be selectively antagonized, without affecting the excitatory responses.

It is concluded that (a) responses of cortical neurones to adrenoceptor agonists are mediated by both α‐ and β‐receptors; (b) these α‐ and β‐receptors give rise to opposite effects: the α‐receptors being excitatory and the β‐receptors being inhibitory; and (c) responses of many neurones reflect the presence of both types of receptor.
ASPIRIN AT THERAPEUTIC CONCENTRATIONS DOES NOT AFFECT 5‐HYDROXYTRYPTAMINE UPTAKE BY PLATELETS
Authors: DRUMMOND A.H. , MacINTYRE D.E. , OLVERMAN H.J. , GORDON J.L.
Published: July 2012

Aspirin at therapeutic concentrations does not inhibit the uptake of 5‐hydroxytryptamine (5‐HT) by blood platelets nor induce release of 5‐HT from platelets, although platelet aggregation responses to collagen and arachidonic acid (which are dependent on platelet prostaglandin synthesis) are abolished. This does not support an earlier claim that aspirin's effects on platelet function include inhibition of 5‐HT transport.
THE EFFECTS OF NON‐STEROIDAL ANTI‐INFLAMMATORY DRUGS ON CHOLINERGIC AND HISTAMINE‐INDUCED CONTRACTIONS OF GUINEA‐PIG ISOLATED ILEUM
Authors: FAMAEY J.P. , FONTAINE J. , REUSE J.
Published: July 2012

Eleven non‐steroidal anti‐inflammatory drugs (NSAID) reversibly inhibited contractions of the longitudinal muscle of the guinea‐pig isolated ileum induced by acetylcholine, histamine, electrical transmural stimulation and nicotine in this order of increasing potency.

After the addition of prostaglandins E1, E2 or F2α, with partially effective concentrations of NSAID (but not with higher concentrations which almost totally prevented the responses) the inhibitory effects of NSAID were reversibly lost, except for electrically induced contractions and prostaglandin F2α.

The effects of NSAID may be due to actions on biological membranes or on distribution of ions in addition to their inhibitory effect on prostaglandin synthesis. Prostaglandins may reverse the inhibition by non‐selective sensitization of smooth muscle to various agonists.
DISSIMILARITY BETWEEN THE RESPONSES TO ADENOSINE TRIPHOSPHATE OR ITS RELATED COMPOUNDS AND NON‐ADRENERGIC INHIBITORY NERVE STIMULATION IN THE LONGITUDINAL SMOOTH MUSCLE OF PIG STOMACH
Authors: OHGA A. , TANEIKE T.
Published: July 2012

Transmural electrical stimulation (TMS) of longitudinal smooth muscle strips taken from the cardiac portion of the pig stomach produced biphasic responses consisting of initial contractions followed by relaxations. The excitatory component was enhanced by neostigmine and abolished by atropine. After atropine treatment, TMS and nicotine or 1,1‐dimethyl‐4‐phenyl‐piperazinium, caused a relaxation or a relaxation followed by an after‐contraction. All of these responses were abolished or reduced reversibly with tetrodotoxin and cocaine, while hexamethonium only abolished the response to ganglion‐stimulating agents.

The relaxation caused by TMS reached a maximum amplitude at 5–10 Hz, and was entirely resistant to the effects of α‐ and β‐adrenoceptor blocking agents, or a combination of them, and also to guanethidine. These results strongly suggested that the relaxation was elicited by stimulation of intramural non‐adrenergic inhibitory neurones.

In the presence of atropine and guanethidine, adenosine triphosphate (ATP, 5–20 μM) caused only a tonic contraction, and ATP (25–200 μM) or adenosine diphosphate (25–200 μM) produced a contractile response or a biphasic one (tonic contraction preceded by a slight relaxation). Adenosine monophosphate and adenosine caused only the tonic contraction over the range of concentrations (25–200 μM).

Stimulation of the intramural inhibitory neurones of the tissue consistently evoked an inhibitory junction potential, which showed a summation during repetitive stimulation. One the other hand, ATP elicited mainly a small depolarization of a few mV.

When the desensitization to ATP of the muscle was achieved in the presence of atropine and guanethidine, the relaxation induced by stimulation of the non‐adrenergic inhibitory neurones could be evoked without any modification.

Dipyridamole neither potentiated the inhibitory responses due to stimulation of the intramural inhibitory neurones nor showed any consistent effect on the ATP‐induced response.

From these results, it is unlikely that ATP, or any related compound, is the transmitter substance of the intramural inhibitory neurones in the longitudinal smooth muscle of the pig stomach.
MECHANISM OF NICOTINE‐INDUCED RELEASE OF NORADRENALINE FROM ADRENERGIC NERVE ENDINGS
Authors: JAYASUNDAR S. , VOHRA M.M.
Published: July 2012

A study of the mechanism of release of [3H]‐noradrenaline ([3H]‐NA) by nicotine from isolated vas deferens of the rat was made using incubation media of different ionic composition.

Nicotine (20 μg/ml)‐induced release of [3H]‐NA was significantly potentiated in K+‐free Krebs solution as compared to that in normal Krebs‐Ringer solution.

Nicotine‐induced release of [3H]‐NA was significantly reduced in Na+‐deficient Krebs solution (containing only 11 mM Na+) and was abolished in Na+‐free Krebs solution.

In totally depolarized tissues, nicotine failed to cause an outflow of [3H]‐NA but Ca2+ (5 mM) did so.

Nicotine required the presence of Ca2+ in the incubation medium to cause release of [3H]‐NA from adrenergic nerve terminals, the magnitude of release being dependent upon the concentration of Ca2+.

Nicotine‐induced release of [3H]‐NA was demonstrated in high Ca2+, Na+‐free Krebs solution in which all Na+ had been replaced with Ca2+.

It is concluded that nicotine increases the membrane permeability to both Na+ and Ca2+. It is also suggested that the increase in permeability to Ca2+ alone is not sufficient but a local depolarizing action of nicotine is necessary to cause release of noradrenaline from adrenergic nerve endings.
THE EFFECTS OF INTRAVENOUS ANAESTHETICS ON THE CARDIOVASCULAR SYSTEM OF THE RABBIT
Authors: McGRATH J.C. , MacKENZIE J.E.
Published: July 2012

A pithed rabbit preparation is described that allows selective stimulation of the vertebral outflows.

The responses to stimulation of sympathetic vasopressor fibres were blocked by hexamethonium and phentolamine but potentiated by cocaine, whereas the responses to stimulation of cardio‐accelerator fibres were blocked by propranolol.

Ketamine, althesin and pentobarbitone enhanced the effects of noradrenaline and attenuated the effects of sympathetic nerve stimulation. Thiopentone enhanced the effects of both noradrenaline and sympathetic nerve stimulation.

In pithed rabbits a transient, dose‐related cardiovascular depression was produced by each agent irrespective of whether vasomotor tone was present whereas in decerebrate rabbits the corresponding cardiovascular depression was longer lasting.

It is concluded that the cardiovascular depression produced by intravenous anaesthetics in intact rabbits is due to a combination of central and peripheral effects.
CENTRAL AND PERIPHERAL NORADRENALINE IN THE TWO KIDNEY MODEL OF RENOVASCULAR HYPERTENSION IN THE RAT
Authors: DARGIE H.J. , FRANKLIN S.S. , REID J.L.
Published: July 2012

Plasma noradrenaline concentrations were similar in rats following unilateral renal arterial constriction (two kidney Goldblatt model) and in sham‐operated control rats.

The development of hypertension was not affected by pretreatment with intracisternal injections of 6‐hydroxydopamine.

These data suggest that sympathetic mechanisms do not contribute to the development of hypertension in this model.
THE RELATIONSHIP BETWEEN ENERGY METABOLISM AND THE ACTION OF INHIBITORS OF HISTAMINE RELEASE
Authors: GARLAND L.G. , JOHANSEN T.
Published: July 2012

Dextran‐induced release of histamine from rat mast cells was inhibited equally in complete and glucose‐free Tyrode solution by doxantrazole (0.03‐3 μmol/l), theophylline (0.1–3 mmol/l) and dicumarol (0.01–10 μmol/litre).

Doxantrazole (3 μmol/l), theophylline (3 mmol/l) and dicumarol (10 μmol/l) did not reduce the adenosine 5′‐triphosphate (ATP) content of mast cells in glucose‐free medium. Higher concentrations of dicumarol (56–100 μmol/l) markedly reduced the cellular ATP content. This reduction was reversed by glucose.

Papaverine was a more potent inhibitor of histamine release from mast cells incubated in glucose‐free solution than in complete Tyrode solution (dose‐ratio = 20). Like antimycin A (1 μmol/l), papaverine (3 μmol/l) caused a depletion of mast cell ATP that was greater in the absence (85%) than in the presence (25%) of extracellular glucose.

These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism. In contrast, papaverine probably inhibits release by depleting ATP that is required for exocytosis.

Inhibition of histamine release by dibutyryl cyclic adenosine 3,5′‐monophosphate (1–3 mmol/l) was significantly greater when cells were incubated in complete rather than in glucose‐free medium.
THE ANTIDYSRHYTHMIC AMINOSTEROID, ORG 6001, REDUCES THE ST‐SEGMENT ELEVATION PRODUCED BY CORONARY OCCLUSION IN THE DOG
Authors: MARSHALL R.J. , PARRATT J.R.
Published: July 2012

ST‐segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open‐chest anaesthetized dogs. This was greatly reduced by the prior administration of the antidysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the extent and degree of myocardial ischaemia or to prevention of K+ egress from ischaemic cells.
RESPONSES OF MOTONEURONES TO ELECTROPHORETICALLY APPLIED DOPAMINE
Authors: BARASI S. , ROBERTS M.H.T.
Published: July 2012

The effect of electrophoretically applied dopamine upon motoneurone excitability has been investigated. Field potentials originating from antidromically activated motoneurones were recorded from the ventral horn of the rat lumbar spinal cord.

Field potentials showed an increase in amplitude following electrophoretic application of dopamine. Dopamine was shown to be less potent than noradrenaline and 5‐hydroxytryptamine in producing these changes.

Measurement of the transport number of dopamine suggests that the relatively low potency of dopamine cannot be attributed to differences in ionic mobilities between the amines.

Electrophoretic application of α‐flupenthixol was shown to discriminate between dopamine and 5‐hydroxytryptamine responses. Dopamine responses were profoundly reduced.

Electrophoretically applied α‐flupenthixol also discriminated between dopamine and noradrenaline. Noradrenaline responses were consistently potentiated by α‐flupenthixol. The possibility is discussed that dopamine may not merely be a precursor for noradrenaline in the rat spinal cord.
THE GENERATION OF NERVE AND MUSCLE REPETITIVE ACTIVITY IN THE RAT PHRENIC NERVE‐DIAPHRAGM PREPARATION FOLLOWING INHIBITION OF CHOLINESTERASE BY ECOTHIOPATE
Authors: MORRISON J.D.
Published: July 2012

Simultaneous extracellular recordings were made from two end‐plate zones of the isolated diaphragm and from the phrenic nerve of the rat in response to stimulation of the nerve. The contractions of the diaphragm were also recorded.

In the curarized diaphragm, the introduction of ecothiopate, a non‐competitive inhibitor of cholinesterase, caused a threefold increase in the amplitude of the end‐plate current and an eightfold increase in the duration at half the peak amplitude.

In the non‐curarized diaphragm, the introduction of ecothiopate caused the generation of repetitive activity (RA) in first the phrenic nerve: this was then followed by RA in the diaphragm. At that stage, nerve RA possessed a shorter latency than muscle RA. The generation time for nerve RA was 1.6 ms and for mRA, it was 2.7 milliseconds.

Nerve RA was more labile than muscle RA; it was readily abolished by increasing the frequency of stimulation, by magnesium, by tubocurarine or by high concentrations of ecothiopate, whereas muscle RA was still generated. Steady exposure to acetylcholine abolished both forms of RA.

Two competitive inhibitors of cholinesterase, neostigmine and ambenonium, were also shown to evoke RA in nerve and muscle. The generation times for nerve RA and muscle RA were similar to those following ecothiopate.

It was concluded that nerve RA and muscle RA were generated after the inhibition of cholinesterase by ecothiopate as a result of the prolonged action of acetylcholine upon cholinoceptive sites on the nerve terminal and motor endplate respectively. A direct excitatory action of ecothiopate upon the phrenic nerve terminals was excluded.
THE EFFECT OF Δ9‐TETRA‐HYDROCANNABINOL ON BODY TEMPERATURE AND BRAIN AMINE CONCENTRATIONS IN THE RAT AT DIFFERENT AMBIENT TEMPERATURES
Authors: FENNESSY M.R. , TAYLOR D.A.
Published: July 2012

Rats were injected intravenously with 2 mg/kg (–)‐trans‐Δ9‐tetrahydrocannabinol (Δ9‐THC) at ambient temperatures of 4°, 21°, 31° and 37°C.

The general behaviour exhibited by rats treated with Δ9‐THC was similar at all four ambient temperatures.

Body temperatures were recorded continuously before and after drug administration. At 4° and 21°C, Δ9‐THC caused hypothermia whereas no change in body temperature occurred at 31° and 37°C.

The concentrations in the whole brain of noradrenaline (NA), dopamine, 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) were determined spectrophotofluorimetrically 1 h after drug administration. At 4°C Δ9‐THC caused an increase of 5‐HT, at 21°C an increase of 5‐HIAA, at 31°C an increase of 5‐HIAA and a decrease of NA, and at 37°C an increase of 5‐HT and 5‐HIAA.

At all ambient temperatures, Δ9‐THC increased the brain levels of 5‐HT and/or 5‐HIAA. A correlation between the Δ9‐THC‐induced hypothermic response and the possible alteration of brain 5‐HT metabolism cannot be excluded.
THE EFFECTS OF ADENINE NUCLEOTIDES ON CUTANEOUS AFFERENT NERVE ACTIVITY
Authors: BLEEHEN TIRZA
Published: July 2012

The activity produced by the adenine nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) and by potassium, acetylcholine (ACh), 5‐hydroxytryptamine (5‐HT) and bradykinin when applied to an exposed blister base on the ear of anaesthetized rabbits or intra‐arterially to anaesthetized cats was investigated in multiple strands dissected from the auricular‐temporal and saphenous nerves of rabbits and cats, respectively.

In the rabbit preparation potassium and the adenine nucleotides produced activity in the nerve fibres. The effects of these substances were produced in comparable dose ranges; threshold effects being produced by potassium at a concentration of 13 mm and by ADP at a concentration of 4 mm. ACh, 5‐HT and bradykinin were inactive at similar or higher concentrations.

In the cat preparation all the substances tested produced activity in the nerve fibres. The adenine nucleotides were comparatively less potent than ACh, 5‐HT or bradykinin, but had greater potency than potassium.

It was concluded that the adenine nucleotides do possess effects on afferent nerve terminals or fibres and thus resemble other known algogenic substances such as potassium, ACh, 5‐HT and bradykinin.
A 5‐HYDROXYTRYPTAMINE‐LIKE MODE OF ANORECTIC ACTION FOR 6‐CHLORO‐2‐[1‐PIPERAZINYL]‐PYRAZINE (MK‐212)
Authors: CLINESCHMIDT BRADLEY V. , McGUFFIN JODIE C. , PFLUEGER A. BARBARA , TOTARO JAMES A.
Published: July 2012

The mechanism of the reduction in food consumption elicited by 6‐chloro‐2‐[1‐piperazinyl]‐pyrazine (MK‐212) administered systemically was investigated in the rat. (+)‐Fenfluramine and (+)‐amphetamine were included in some studies for comparative purposes.

Pretreatment with methergoline, a 5‐hydroxytryptamine (5‐HT) antagonist, reduced the magnitude of the anorectic effect of 1.5 and 3 mg/kg of MK‐212, while the anti‐5‐HT agents, cyproheptadine and cinanserin, were likewise effective against the 3 mg/kg dose.

Xylamidine, an antagonist of 5‐HT that penetrates poorly into the central nervous system, completely blocked the decrease in food intake caused by 5‐HT administered peripherally, while not antagonizing an equianorectic dose of MK‐212.

Reduction of brain 5‐HT by intraventricular injection of 5,6‐dihydroxytryptamine, intraperitoneal administration of p‐chloroamphetamine or placement of a lesion in the region of the median raphe nucleus diminished the anorectic response to 3 mg/kg of MK‐212. The anorectic effect of amphetamine was reduced by p‐chloroamphetamine or lesion in the raphe, but not by 5,6‐dihydroxytryptamine. The decrease in food consumption produced by 1.5 mg/kg of MK‐212 was antagonized by prior treatment with p‐chloroamphetamine, but not by 5,6‐dihydroxytryptamine.

Haloperidol, which blocks receptors for dopamine, antagonized the anorexigenic effect of amphetamine, but was ineffective in offsetting the action of MK‐212, 3 mg/kg.

Pretreatment with chlorimipramine to inhibit the 5‐hydroxytryptaminergic uptake mechanism did not affect the anorectic response to 3 mg/kg of MK‐212, whereas the response to fenfluramine was diminished.

The results indicate that the anorectic action of MK‐212 involves a 5‐HT‐like component which is more evident at the higher dose level of the compound. The anorexigenic property of MK‐212 may depend, at least partly, upon the integrity of 5‐HT‐containing neurones in the central nervous system.
SPECIES DIFFERENCES IN POSTGANGLIONIC MOTOR TRANSMISSION TO THE RETRACTOR PENIS MUSCLE
Authors: AMBACHE N. , KILLICK S.W.
Published: July 2012

Graded motor responses were elicited in isolated, desheathed, thin strips of dog, horse, pig and sheep retractor penis (RP) muscles by field stimulation with trains of 0.2 ms pulses at 10 hertz. These twitches were shown to be neurogenic in all four species, by their prompt extinction in tetrodotoxin.

α‐Adrenoceptor blocking drugs abolished the contractile response to noradrenaline and to tyramine in all four species.

Motor transmission was wholly adrenergic in the horse as in the dog RP because phentolamine rapidly abolished the electrically induced twitches in both these species; but in the pig and in the sheep RP a large proportion of the motor transmission was unaffected by phentolamine given in many times the concentration required to abolish matching noradrenaline‐induced contractions.

Because of the occurrence of periodic spasms in sheep preparations, further investigation of the phentolamine‐resistant transmission was confined to the pig RP. Its responses were shown to be entirely postganglionic in origin because they were unaffected by pentolinium.

In the pig RP a considerable proportion of the phentolamine‐resistant motor transmission persisted after combined blockade of α‐ and β‐adrenoceptors by phenoxybenzamine plus propranolol and was more resistant to guanethidine and bretylium than the motor transmission to the dog RP; it was not extinguished after reserpine treatment.

The pig RP is contracted by histamine but is rather insensitive to acetylcholine, 5‐HYDROXYTRYPTAMINE and adenosines‐triphosphate. The motor transmission remained unaffected after responses to these substances were blocked by the following antagonists, given alone or in combination: mepyramine, burimamide, atropine, (+)‐tubocurarine, methysergide and 2–2′‐pyridylisatogen tosylate.
ROLE OF PLATELETS IN ASPIRIN‐SENSITIVE BRONCHOCONSTRICTION IN THE GUINEA‐PIG; INTERACTIONS WITH SALICYLIC ACID
Authors: LEFORT JEAN , VARGAFTIG BERNARDO B.
Published: July 2012

The bronchoconstriction caused in the guinea‐pig by arachidonic acid (AA), bradykinin, adenosine diphosphate (ADP) and adenosine triphosphate (ATP) was correlated with effects on platelets. ATP and ADP produced a brief thrombocytopenia and AA a more prolonged one. Bradykinin had no effect on platelets.

Aspirin inhibited bronchoconstriction and thrombocytopenia produced by AA and part of the bronchoconstriction produced by ATP, but had no effect against ADP. Thrombocytopenia produced by ADP and ATP was not affected by aspirin or indomethacin.

Platelet depletion by antiserum prevented bronchoconstriction in response to ADP and to ATP, but not in response to bradykinin or to AA, showing that platelets are not involved in aspirin‐sensitive bronchoconstriction. Infusions of ADP reduced bronchoconstriction and thrombocytopenia in response to ADP itself and to ATP, but not to AA. Bronchoconstriction by ADP or ATP involves an action on platelets. Only that due to ATP is partially dependent on the activity of prostaglandin synthetase.

ATP induced aggregation in vitro in guinea‐pig platelet‐rich plasma (PRP). Rabbit PRP responded only when ATP was first incubated with guinea‐pig plasma. The aggregating compound formed was probably ADP, since it was destroyed by apyrase. Its formation was not inhibited by aspirin or indomethacin, indicating that aspirin inhibits ATP‐induced bronchoconstriction by a different mechanism.

The aggregating effect of ATP on guinea‐pig platelets was inhibited by concentrations of apyrase that block ADP‐induced aggregation, and potentiated by lower concentrations of apyrase.

Adenosine 5′‐tetraphosphate did not aggregate platelets in vivo or in vitro. In vitro aggregation occurred when apyrase was added, suggesting transformation into ADP. Adenosine 5′‐tetraphosphate and apyrase inhibited aggregation due to ADP, but failed to affect that due to AA. This suggests that aggregation involving products of prostaglandin synthesis does not require ADP.

Salicylic acid did not interfere with bronchoconstriction or aggregation due to AA, but prevented inhibition by aspirin when the weight ratio, salicylic acid:aspirin was 4:1. Salicylic acid may be useful in studies of potential inhibitors of thromboxane A2 synthesis and of thromboxane A2‐depen‐dent processes in vivo and in vitro.
HYPERTHERMIC RESPONSES TO CENTRAL AND PERIPHERAL INJECTIONS OF MORPHINE SULPHATE IN THE CAT
Authors: CLARK WESLEY G. , CUMBY H. RICK
Published: July 2012

The effect of morphine on body temperature was studied in conscious, unrestrained cats provided with implanted third or lateral cerebral ventricular cannulae, jugular venous catheters and retroperitoneal thermocouples.

Intraventricular injections of 2.5–50 μg and intravenous injections of 1–10 mg/kg morphine sulphate produced dose‐related hyperthermic responses. Similar mean increases in body temperature after administration of a given dose were elicited in cats which had not previously received morphine and, provided that tolerance was avoided by spacing injections at least 72 h apart, in cats which received a series of injections of morphine. Morphine was at least 850 times more potent when injected into the third ventricle than when given intravenously. Increasing the dose of morphine sulphate injected into the third ventricle to 1250 μg only prolonged the hyperthermia. Morphine did not produce hypothermia at any dose tested.

Injection of 10 μg morphine sulphate into the third ventricle produced similar hyperthermias at ambient temperatures (tas) of 4–6, 21–23 and 33–36°C. The increase in body temperature was associated with shivering at the lower tas. At the highest ta, shivering was not evoked, but respiratory rate decreased after morphine if it was initially elevated. These results suggest that morphine increased the level at which body temperature was regulated.

Neither metiamide nor indomethacin antagonized morphine so histamine and prostaglandins were apparently not required for the hyperthermic effect.
THE NEURONAL ORIGIN OF PROSTAGLANDIN RELEASED FROM THE RABBIT PORTAL VEIN IN RESPONSE TO ELECTRICAL STIMULATION
Authors: GREENBERG R.
Published: July 2012

Transmural electrical stimulation of the isolated portal vein of the rabbit was accompanied by the release of a prostaglandin‐like substance (PLS). Thin layer chromatography coupled with bioassay indicated that this substance was probably prostaglandin E2 (PGE2).

Indomethacin potentiated the response of the portal vein to electrical stimulation at 2 Hz and abolished the release of the PLS.

There was no significant change in the amount of PLS released from the portal vein in response to electrical stimulation at 2 Hz when the contractile response of the portal vein was prevented by pretreatment with phentolamine or guanethidine.

In vitro denervation of the portal vein with 6‐hydroxydopamine or the omission of Ca2+ from the bathing solution caused a significant reduction in the amount of PLS released from the portal vein in response to electrical stimulation at 2 hertz.

It is concluded that electrical stimulation of the isolated portal vein of the rabbit is accompanied by the release of a PLS, probably PGE2, from a neuronal source. The synthesis and release of the PLS is Ca2+‐dependent.
PURINERGIC INNERVATION OF THE GUINEA‐PIG URINARY BLADDER
Authors: BURNSTOCK G. , COCKS T. , CROWE R. , KASAKOV L.
Published: July 2012

A number of criteria for considering adenosine 5′‐triphosphate (ATP) as a neurotransmitter in the guinea‐pig urinary bladder have been examined. In addition, the effect of tachyphylaxis to ATP on the response to non‐adrenergic, non‐cholinergic nerve stimulation has been re‐examined.

Quinacrine fluorescence histochemistry revealed a population of nerve fibres, ganglion cells, and nerve bundles in the bladder which were not seen in either the iris or vas deferens, where adrenergic and cholinergic nerves predominate. The distribution and morphology of the quinacrine‐positive nerves in the bladder were different from those observed with catecholamine fluorescence and cholinesterase histochemistry, and were unaffected by chemical sympathectomy.

Release of ATP from the bladder during stimulation of intramural excitatory nerves, in the presence of atropine and guanethidine increased to 3–12 times prestimulation levels. Tetrodotoxin abolished both the contractile response and the increase in ATP release resulting from intramural nerve stimulation. There was no increase in ATP release during contraction resulting from direct muscle stimulation following nerve paralysis with tetrodotoxin.

Sympathectomy with 6‐hydroxydopamine did not affect release of ATP in response to intramural nerve stimulation.

Release of ATP was dependent on the concentration of calcium ion in the medium.

Contractions in response to non‐adrenergic, non‐cholinergic intramural nerve stimulation were closely mimicked by ATP, but not by acetylcholine or histamine.

Adenosine and dipyridamole reduced the contractions to both ATP and non‐cholinergic nerve stimulation.

2–2′‐Pyridylisatogen was not a specific blocker of either ATP or intramural nerve stimulation in the guinea‐pig bladder. 2‐Substituted imidazolines initiated spontaneous activity making it impossible to assess any blocking action that they may have had.

Prostaglandins (E1 E2 and F2a) gave weak, slow contractions and an increase in spontaneous activity. Both the response to ATP and non‐adrenergic, non‐cholinergic nerve stimulation were greatly potentiated in the presence of prostaglandins.

In the presence of indomethacin the response to non‐adrenergic, non‐cholinergic nerve stimulation was virtually abolished following desensitization to ATP.
EFFECT OF MECAMYLAMINE ON THE FATE OF DOPAMINE IN STRIATAL AND MESOLIMBIC AREAS OF RAT BRAIN; INTERACTION WITH MORPHINE AND HALOPERIDOL
Authors: AHTEE LIISA , KAAKKOLA SEPPO
Published: July 2012

The effects of the nicotinic cholinoceptor blocking drug, mecamylamine (alone or in combination with morphine or haloperidol) were investigated on the striatal homovanillic acid (HVA) concentration and on the α‐methyl‐p‐tyrosine (AMPT)‐induced depletion of striatal or mesolimbic dopamine content in the brain of rats.

Mecamylamine (2 mg/kg) alone did not alter the striatal HVA concentration, but it reduced the probenecid‐induced accumulation of HVA. Mecamylamine pretreatment reduced the morphine‐and haloperidol‐induced elevation of striatal HVA concentration. Hexamethonium did not alter the striatal HVA concentration when given alone or in probenecid‐ or morphine‐treated rats, whereas pempidine (8 mg/kg) clearly reduced the probenecid‐induced accumulation of HVA in the striatum.

Mecamylamine (2 and 8 mg/kg) slowed the rate of AMPT‐induced depletion of dopamine from the striatum and mesolimbic area both in the brain of control rats and of rats treated with morphine or haloperidol.

Mecamylamine slightly prolonged the cataleptic effect of morphine.

The results indicate that mecamylamine inhibits the release of dopamine both from the striatal and mesolimbic dopaminergic neurones.
THE UPTAKE KINETICS AND METABOLISM OF EXTRANEURONAL NORADRENALINE IN GUINEA‐PIG TRACHEA AS STUDIED WITH QUANTITATIVE FLUORESCENCE MICROPHOTOMETRY
Authors: O'DONNELL STELLA R. , SAAR NILI
Published: July 2012

Extraneuronal uptake of noradrenaline and α‐methylnoradrenaline into single cells of guinea‐pig tracheal smooth muscle have been studied by means of quantitative fluorescence microphotometry.

Fluorescence brightness due to accumulation of α‐methylnoradrenaline was dose‐dependent and was increased by the catechol‐O‐methyltransferase inhibitor drugs, tropolone or β‐thujaplicin (200 μM) but not by 3,4‐dimethoxy‐5‐hydroxybenzoic acid (200 μM).

Fluorescence brightness due to accumulation of noradrenaline was increased if animals were pretreated with the monoamine oxidase inhibitor drug, nialamide.

The study suggests that metabolism of amines by catechol‐O‐methyltransferase and monoamine oxidase can occur subsequent to extraneuronal uptake in guinea‐pig tracheal smooth muscle.

The uptake of noradrenaline into tracheal smooth muscle was concentration‐dependent, saturable, and had a Km of 156 μM.
THE ACTIONS OF SOME VASOACTIVE POLYPEPTIDES AND THEIR ANTAGONISTS ON THE ANOCOCCYGEUS MUSCLE
Authors: GILLESPIE J.S. , McKNIGHT A.T.
Published: July 2012

The action of three polypeptides, bradykinin, substance P and eledoisin known to inhibit vascular smooth muscle has been examined on the anococcygeus muscle of the rat, cat and rabbit.

In the atonic rat muscle, bradykinin and substance P had little or no effect on tone but eledoisin produced a sustained dose‐related contraction which could be abolished by phentolamine (1 μM) and is, therefore, probably an indirect sympathomimetic effect. On the motor response to field stimulation of adrenergic nerves, bradykinin had no effect whereas both substance P and eledoisin reduced this response. The mechanism of action was further analysed with eledoisin by examining its effect on the response to noradrenaline. Eledoisin did not alter the dose‐response curve to noradrenaline and its inhibitory action is likely, therefore, to be presynaptic.

In the rat anococcygeus muscle in which the tone was raised by guanethidine or carbachol, bradykinin and substance P reduced this tone whereas eledoisin continued to exert a motor action. Compared with substance P the inhibitory effect of bradykinin appeared at lower concentrations (threshold 0.01 μg/ml), developed more rapidly and the size of the response was greater.

The effect of bradykinin on the tonically contracted cat and rabbit anococcygeus muscles was examined in addition to that of the rat. In all three species bradykinin caused inhibition and the magnitude of the response was equal to the maximum effect of inhibitory nerve stimulation. None of the peptides affected the inhibitory response to nerve stimulation itself.

The effects of three substances, hesperitin, khellin and apiin, reported in other tissues to antagonize the action of bradykinin were examined both on the inhibitory response to bradykinin and to field stimulation. None of them was able to inhibit either response, although they reduced tone when given by themselves. During these experiments it was found that ethanol antagonized the inhibitory response to field stimulation.

The possibility that bradykinin or some related peptide might play a part in the inhibitory response to nerve stimulation in the anococcygeus is discussed.
β‐ADRENOCEPTOR MEDIATED INHIBITION BY TERBUTALINE OF HISTAMINE EFFECTS ON VASCULAR PERMEABILITY
Authors: O'DONNELL STELLA R. , PERSSON C.G.A.
Published: July 2012

In guinea‐pigs, previously given Evans blue dye intravenously, 13 to 18 intradermal injections of histamine, with or without other drugs, were made into the depilated trunk skin. Dye was then quantitatively extracted from each skin area and the measured absorbance values were used as a measure of vascular leakage of macromolecules.

Histamine (0.5 to 12 nmol) produced dose‐related increases in vascular leakage. These were reduced by terbutaline (1 and 10 nmol) which produced a significant shift in the histamine dose‐response lines to lower absorbance values. The effect of 0.1 nmol of terbutaline was significant only against doses of histamine of less than 2 nmol.

Propranolol (1 nmol and 10 nmol) antagonized the effects of terbutaline. Propranolol, at a dose of 10 nmol but not 1 nmol, itself reduced the responses to 1.5 nmol histamine.

We conclude that the inhibition by terbutaline of histamine‐induced dye leakage in guinea‐pig skin is mediated by stimulation of β‐adrenoceptors and it is suggested that this effect of terbutaline occurs directly on β‐receptors at the vascular leakage site.
VASOACTIVE INTESTINAL POLYPEPTIDE PROMOTES CYCLIC ADENOSINE 3‘,5’‐MONO‐PHOSPHATE ACCUMULATION IN GUINEA‐PIG TRACHEA
Authors: FRANDSEN E.K. , KRISHNA G.A. , SAID S.I.
Published: July 2012

Cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) levels in guinea‐pig tracheal rings increased on incubation with the vasoactive intestinal peptide (VIP). The effect was potentiated by the addition of theophylline. The results suggest that the tracheo‐bronchial relaxant action of VIP may be mediated by stimulation of tracheal adenylyl cyclase.
RELEASE OF VASOPRESSIN BY ENKEPHALIN
Authors: BISSET G.W. , CHOWDREY H.S. , FELDBERG W.
Published: July 2012

Leu‐enkephalin, its stable analogue [D‐Ala2‐D‐Leu5]‐enkephalin and the C‐fragment of lipotropin (β endorphin) injected intravenously in the rat produced anti‐diuretic responses which were inhibited reversibly by naloxone. It was shown for Leu‐enkephalin that injection into the cerebral ventricles was at least ten times more effective than intravenous injection and for [D‐Ala2‐D‐Leu5]‐enkephalin that the antidiuretic response was associated with increased excretion of vasopressin in the urine.
PREVENTION BY GUANETHIDINE ANALOGUES OF OUTPUT OF NORADRENALINE INDUCED BY SODIUM REDUCTION IN RABBIT VENTRICULAR SLICES
Authors: HOSOTANI T. , MISU Y.
Published: July 2012

The prevention by guanethidine and related agents of the output of noradrenaline induced by low sodium was investigated in rabbit ventricular slices. When external NaCl was reduced, the output of noradrenaline into the medium collected at 30 min intervals, increased and the endogenous levels decreased. These changes induced by replacing sodium with sucrose or choline were not affected either by the omission of calcium and addition of 0.5 mm ethylene glycol‐bis(aminoethyl‐ether)N,N,N′,N′ tetra‐acetic acid (EGTA) or by an increase in the calcium concentration to 10 mm 30 min before sodium deprivation.

Guanethidine 4 × 10−6 and 4 × 10−5m and 4–7‐exo‐methylene‐hexahydroisoindoline‐ethyl guanidine (No. 865‐123) 4 × 10−5 to 8 × 10−4m inhibited, in a dose‐dependent manner, increases in output of noradrenaline induced by reduction of sodium to 18 mm, while guanethidine 8 × 10−5m and high doses of bretylium produced no inhibition: the latter two released noradrenaline.

The inhibitory actions of guanethidine 4 × 10−5m and No. 865‐123 4 × 10−4m were prevented by tetracaine 3.3 × 10−4m, which per se did not modify the output of noradrenaline induced by 18 mm sodium.

Accumulation of guanethidine and No. 865‐123 in ventricular slices was greater than that noted in striated muscle slices and was dose‐, time‐ and temperature‐dependent. Tetracaine 3.3 × 10−4m did not prevent the accumulation of guanethidine 4 × 10−5m and No. 865‐123 1.1 × 10−6 to 4 × 10−4m.

The guanidine derivatives appear to increase the permeability of adrenergic nerve endings to sodium ions.
THE POSTNATAL DEVELOPMENT OF ADRENOCEPTOR RESPONSES TO AGONISTS AND ELECTRICAL STIMULATION IN RAT ISOLATED ATRIA
Authors: STANDEN N.B.
Published: July 2012

Isolated right and left atria from rats of ages ranging from newborn to adult were used to measure chronotropic and inotropic responses to noradrenaline, isoprenaline, tyramine, and electrical stimulation of intramural nerves.

Right atria from newborn animals showed increases in rate with noradrenaline, isoprenaline, and tyramine which did not differ significantly from those of atria from adults. The ED50 values for the chronotropic actions of noradrenaline and isoprenaline were not significantly different at any age from the values in adult preparations.

Paced left atria from newborn rats showed well developed positive inotropic responses to noradrenaline and isoprenaline. Newborn left atria (and those from 1 and 2 week old animals) were supersensitive to noradrenaline but not to isoprenaline.

Left atria from newborn animals showed very small inotropic responses to both tyramine and field stimulation of intramural nerves. These responses developed progressively with age over the first three weeks of life. The results are discussed with respect to the development of cardiac β‐adrenoceptors and of cardiac sympathetic innervation.
THE INFLUENCE OF L‐TRYPTOPHAN AND MONOAMINE OXIDASE INHIBITORS ON CATECHOLAMINE METABOLISM IN RAT BRAIN
Authors: ECCLESTON D. , NICOLAOU N.
Published: July 2012

L‐Tryptophan (100 mg/kg) was administered to rats with or without pretreatment with a monoamine oxidase inhibitor and the concentration of 5‐hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3‐methoxy 4‐hydroxyphenyl glycol, normetanephrine, noradrenaline and dopamine measured in whole brain one hour later.

L‐Tryptophan increased the concentration of 5‐hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3‐methoxy 4‐hydroxyphenyl glycol and normetanephrine. The concentration of noradrenaline did not change whilst that of dopamine increased significantly.

In animals pretreated chronically with a monoamine oxidase inhibitor, tryptophan increased the concentration of dihydroxyphenylacetic acid and homovanillic acid compared to monoamine oxidase alone.

The results suggest either a release of dopamine and noradrenaline by 5‐hydroxytryptamine, with a compensatory increase in their synthesis, or an increase in the firing of dopaminergic and noradrenergic neurones after L‐tryptophan.
MODELS FOR INVESTIGATING THE AETIOLOGY OF CEREBRAL ARTERIAL SPASM: COMPARATIVE RESPONSES OF THE HUMAN BASILAR ARTERY WITH RAT COLON, ANOCOCCYGEUS, STOMACH FUNDUS, AND AORTA AND GUINEA‐PIG ILEUM AND COLON
Authors: BOULLIN D.J. , HUNT TERESA M. , ROGERS A.T.
Published: July 2012

The pharmacological similarity between human basilar artery and a number of isolated tissues (rat colon, anococcygeus, stomach fundus and aorta and guinea‐pig ileum and colon) has been assessed during investigations of the aetiology of cerebral arterial spasm.

The responses of each of the six tissues to human normal and abnormal cerebrospinal fluid (CSF) and to human serum were compared with those of the human isolated basilar artery.

These studies revealed the presence of a vasodilator factor in CSF from subarachnoid haemorrhage patients and several tissues may be of use for further work in identifying the vasoactive substances in CSF.

No tissue displayed exactly the same spectrum of biological reactivity as the human basilar artery. The rat stomach fundus showed the closest similarity and was further studied for similarities in drug‐induced responses.

The rat stomach fundus, like the human basilar artery, was contracted by 5‐hydroxytryptamine, prostaglandin F2a and histamine and relaxed by dopamine. However, noradrenaline relaxed the fundus but contracted the basilar artery.