bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF OESTRADIOL AND PROGESTERONE ON THE in vitro PRODUCTION OF PROSTAGLANDIN F2α BY THE GUINEA‐PIG UTERUS
Authors: NAYLOR B. , POYSER N.L. 
Published: July 2012

The effects of oestradiol and progesterone on the production of prostaglandin F2α by the guinea‐pig uterus in vitro have been studied.
Ovariectomized guinea‐pigs were treated with oestradiol benzoate, progesterone, or a combination of these hormones. The uteri were homogenized and incubated and the prostaglandin F2α produced was measured by radioimmunoassay or combined gas chromatography‐mass spectrometry (g.c.‐m.s.). Oestradiol treatment or progesterone followed by oestradiol caused a significant increase in prostaglandin F2α synthesis compared with control values, whereas progesterone treatment caused no significant increase.
The uteri from guinea‐pigs on day 7 of the oestrous cycle were split into four parts, and each part homogenized and incubated either alone or in the presence of oestradiol‐17β, progesterone, or a combination of these hormones. Prostaglandin F2α was measured by g.c.‐m.s. Oestradiol was found to increase prostaglandin F2α synthesis by the uterus whereas progesterone had no effect. However, progesterone did inhibit the response to oestradiol.
Oestradiol treatment of the guinea‐pig uterus causes an increase in capacity to produce prostaglandin F2α in vitro. The role of progesterone is difficult to interpret.
PRESSOR EFFECTS OF TRYPTAMINE ANALOGUES
Authors: BOSIN T.R. , HIXSON E. JANE , MAICKEL R.P. 
Published: July 2012

Methylation of tryptamine in the 1‐position had little effect on the potency of the drug as a pressor agent in the intact anaesthetized rat.
In contrast, substitution of a benzo[b]thiophene ring system for the indole ring decreased the pressor activity.
Pretreatment of the animals with reserpine reduced the pressor effect of tryptamine and its benzo[b]thiophene analogue while increasing the effect of the 1‐methylindole analogue.
Pretreatment with phenoxybenzamine reduced the pressor effect of all three compounds.
TOLERANCE TO THE CARDIOVASCULAR EFFECTS OF Δ9‐TETRAHYDROCANNABINOL IN THE RAT
Authors: ADAMS M.D. , CHAIT L.D. , EARNHARDT J.T. 
Published: July 2012

Daily intraperitoneal injections of Δ9‐tetrahydrocannabinol (Δ9‐THC, 10 mg/kg) resulted in tolerance to the effects of the cannabinoid on body weight and body temperature within 1–2 weeks of treatment.
Tolerance failed to develop to the suppression of spontaneous motor activity produced by Δ9‐THC during 28 days of treatment with the cannabinoid (10 mg/kg, i.p. per day).
Following treatment with vehicle for 28 days, intravenous administration of Δ9‐THC in anaesthetized rats produced a transient pressor response followed by a sustained hypotension and bradycardia.
Tolerance to the hypotensive and negative chronotropic responses to intravenous Δ9‐THC was readily apparent in animals which had received daily intraperitoneal injections of Δ9‐THC (10 mg/kg) for 28 days.
Tolerance failed to develop to the pressor actions of intravenous Δ9‐THC after 28 days of pretreatment.
There was no difference in the pressor response to intravenous noradrenaline in vehicle‐treated animals (1.0 ml/kg, i.p., per day for 28 days) and Δ9‐THC‐treated animals (10 mg/kg, i.p., per day for 28 days).
RESPONSES OF NEURONES IN THE CEREBRAL CORTEX AND CAUDATE NUCLEUS TO AMANTADINE, AMPHETAMINE AND DOPAMINE
Authors: STONE T.W. 
Published: July 2012

Dopamine, amantadine and amphetamine have been applied directly by microiontophoresis to single neurones in the caudate nucleus ana cerebral cortex of rats anaesthetized with urethane.
The predominant response to all three agents was a depression of neuronal firing rate. The responses to dopamine and amantadine could be antagonized by the dopamine receptor blocking agent, chlorpromazine.
Amantadine did not cause any potentiation of dopamine responses, suggesting that inhibition of amine uptake was not responsible for its effects.
The responses of pyramidal tract cells in the cerebral cortex to dopamine, amphetamine and amantadine were compared in control groups of rats and rats pretreated with reserpine (10 mg/kg i.p.) or α‐methyl‐p‐tyrosine methyl ester (200 mg/kg i.p.). The reduction of cortical catecholamine concentrations was confirmed by a direct fluorimetric assay method.
Responses to dopamine were unaltered in the amine‐depleted animals compared with controls. Responses to amantadine and amphetamine were reduced but not abolished.
It is concluded that amantadine acts partly by releasing catecholamines from neuronal stores. The residual responses to amantadine and amphetamine may be the result of a direct postsynaptic receptor stimulation.
THE INFLUENCE OF MOTOR NERVE TETANIZATION ON THE EFFECT OF ORGANOPHOSPHORUS CHOLINESTERASE INHIBITORS ON NEUROMUSCULAR TRANSMISSION
Authors: DANILOV A.F. , IVANOV YU.J. , MICHELSON M.J. 
Published: July 2012

The changes in the activity of synaptic cholinesterases (ChE) of the ant. tibial muscle in the anaesthetized cat were detected by recording the changes of the blocking activity of acetylcholine (ACh) and comparing them with the blocking activity of carbaminoylcholine (carbachol) injected intra‐arterially or intravenously. After the administration of organophosphorus inhibitors (OPI) of ChE the ACh blocking dose diminished 500 to 2000‐fold but the carbachol blocking dose did not change. In 4–6 h after the injection of OPI the ACh blocking dose increased again 8 to 15‐fold, but the dose of carbachol still remained unchanged. The transmission of high frequency impulses improved after OPI in parallel with the decrease of the ACh blocking activity. Thus the synaptic ChE is partly restored in a few hours after its irreversible inhibition with OPI.
Tetanization of the motor nerve (50–60 Hz, 10 min), started simultaneously with the intravenous injection of OPI (armine, Gd‐42), diminished the impairment of neuromuscular transmission. On the side of tetanization the ACh blocking action was less pronounced and the transmission of high frequency impulses better than on the control side. Thus the tetanization produced some protection of synaptic ChE against inhibition by OPI. The protective effect of tetanization was absent when the tetanization was performed before the injection of OPI or was started 10–20 min after the injection of OPI.
The protective effect of tetanization was also observed on the isolated phrenic nerve diaphragm preparation of the rat.
The possible mechanisms of the protective effect of tetanization are discussed.
UPTAKE OF 5‐HYDROXYTRYPTAMINE BY RAT BLOOD PLATELETS AND ITS INHIBITION BY ADENOSINE 5‘‐DIPHOSPHATE
Authors: DRUMMOND A.H. , GORDON J.L. 
Published: July 2012

The uptake of 5‐hydroxytryptamine (5‐HT) by rat blood platelets in citrated plasma was linear for at most 10 s and was substantially complete within 3 minutes.
Adenosine 5′‐diphosphate (ADP) was a potent inhibitor of 5‐HT uptake (Ki = 0.38 μm) and kinetic analysis revealed that the inhibition was not competitive.
Inhibition of 5‐HT uptake by ADP was abolished in the presence of prostaglandin E1 and 2‐n‐amylthio‐AMP, which also inhibit the stimulant actions of ADP on blood platelets.
It is concluded that ADP could inhibit 5‐HT uptake by changing the Na+/K+ distribution across the cell membrane, and the biological significance of this is discussed.
THE DISTRIBUTION AND KINETICS OF SULPHACETAMIDE IN LEUKAEMIC MICE
Authors: MARCHAND C. , NADEAU D. 
Published: July 2012

During the first 90 min following oral administration of sulphacetamide, there was a rapid decline in plasma drug concentration in control mice whereas a progressive increase in sulphacetamide concentration was observed in leukaemic mice.
Similar changes in the kinetics of sulphacetamide distribution were observed in the liver, spleen and muscle.
While the concentration of sulphacetamide remained quite constant in the brain and fat tissue of control mice, a progressive increase in drug concentration was observed in the brain and fat tissue of leukaemic mice.
Some of these changes in the kinetics of sulphacetamide tissue distribution are compatible with delay in gastrointestinal absorption of the drug and its accumulation in the ascitic fluid.
EFFECTS OF MAZINDOL, A NON‐PHENYLETHYLAMINE ANOREXIGENIC AGENT, ON BIOGENIC AMINE LEVELS AND TURNOVER RATE
Authors: CARRUBA M.O. , GROPPETTI A. , MANTEGAZZA P. , VICENTINI L. , ZAMBOTTI F. 
Published: July 2012

Mazindol is a new anorexigenic agent which possesses a different chemical structure from that of phenylethylamines, but shows a pharmacological profile similar to that of (+)‐amphetamine.
Mazindol neither altered whole brain monoamine levels (noradrenaline (NA), dopamine, 5‐hydroxytryptamine (5‐HT)) nor changed NA levels in the hypothalamus or dopamine levels in the caudate nucleus.
Mazindol enhanced dopamine turnover rate in the caudate nucleus, as shown by the increased rate of dopamine decline after blockade of catecholamine synthesis by α‐methyl‐p‐tyrosine and decreased the conversion index of [3H]‐tyrosine into brain NA.
Mazindol administration did not modify pargyline‐induced decline of 5‐hydroxyindoleacetic acid suggesting that 5‐HT turnover is not altered by this drug.
UPTAKE OF 5‐HYDROXYTRYPTAMINE IN DIFFERENT PARTS OF THE BRAIN OF THE RABBIT AFTER INTRAVENTRICULAR INJECTION
Authors: DOW R.C. , LASZLO I. 
Published: July 2012

The uptake of 5‐hydroxytryptamine (5‐HT) was investigated in different areas of the rabbit brain (anterior hypothalamus, the raphe, the region of the substantia nigra, several cortical areas and the medulla oblongata) after intraventricular injection in pargyline pretreated animals by the formaldehyde‐induced histochemical fluorescence method.
The distribution of fluorescence showed that the uptake of 5‐HT, after circulation in the cerebrospinal fluid, caused a general increase in intensity of green yellow to yellow background fluorescence. There was an increased fluorescence in the nerve terminals, but no uptake occurred either in the cell bodies of neurones or in the glial cells.
THE RELATIONSHIP BETWEEN CALCIUM AND INCREASED SENSITIVITY OF RABBIT AORTAE FOUR HOURS AFTER RESERPINE
Authors: CARRIER O. , HESTER R.K. 
Published: July 2012

Four hours after reserpine, rabbit aortic strips were supersensitive to acetylcholine, isoprenaline and noradrenaline. The threshold concentration of the drugs necessary to induce a response was less and the maximum tension developed by the tissues was greater than in control strips.
Reserpine‐treatment potentiated the contractile responses to CaCl2.
Reserpine‐treatment resulted in an increase in calcium uptake and an increase in the slow component of 45Ca2+ efflux.
After resperine‐treatment, the rate of relaxation from a potassium‐induced contraction was decreased.
It is concluded that reserpine‐induced supersensitivity is related to an enhanced ability of the tissue to retain and utilize calcium.
COMPARISON OF THE ACTIONS OF ACEBUTOLOL, PRACTOLOL AND PROPRANOLOL ON CALCIUM TRANSPORT BY HEART MICROSOMES AND MITOCHONDRIA
Authors: DHALLA N.S. , LEE S.L. 
Published: July 2012

The effects of acebutolol, practolol and propranolol (0.5‐3 mm) on calcium uptake, calcium binding and ATPase activities of the rabbit and rat heart microsomal and mitochondrial fractions were investigated.
Dose‐response and time course experiments revealed that propranolol greatly inhibited microsomal and mitochondrial calcium uptake whereas both acebutolol and practolol showed slight depressant effects.
The ATPase activities of microsomal and mitochondrial fractions were decreased by acebutolol, practolol and propranolol; however, the latter agent was more effective than the other two.
The inhibitory effects of acebutolol, practolol and propranolol on mitochondria and microsomes were not antagonized by adrenaline.
Propranolol decreased calcium binding by the microsomal fraction only, whereas acebutolol and practolol had no effect on microsomal or mitochondrial calcium binding.
The sensitivity of the rabbit heart subcellular fractions to the β‐adrenoceptor blocking drugs was similar to that of the rat heart; however, the calcium uptake and ATPase activities of microsomes were more sensitive to propranolol than mitochondria in both species.
Perfusion of rat hearts with 0.2‐1 mm propranolol decreased contractile force, and microsomal and mitochondrial fractions obtained from these hearts accumulated less calcium in comparison to the control. On the other hand, acebutolol and practolol (0.2‐1 nm) had no appreciable effects on contractile force or subcellular fractions under similar conditions.
The negative inotropic effect of propranolol may partly be due to its inhibitory actions on calcium transport by subcellular organelles of the myocardium; the depressant action of propranolol on calcium transport is unlikely to be due to its β‐adrenoceptor blocking property.
INDIRECT AND DIRECT INHIBITION OF DOPAMINE β‐HYDROXYLASE BY AMPHETAMINE IN STORAGE VESICLES AND SYNAPTOSOMES
Authors: LAU C. , SLOTKIN T.A. 
Published: July 2012

To elucidate the mechanism by which amphetamine produces a functional inhibition of dopamine β‐hydroxylase (DBH), the actions of amphetamine on amine uptake and β‐hydroxylation were examined in isolated adrenal storage vesicles and in whole brain synaptosomes of the rat.
Amphetamine produces a competitive inhibition of catecholamine incorporation into adrenal vesicles with a Ki of 279 μm; this action of the drug accounted for slightly less than half of the total inhibition of β‐hydroxylation in the vesicles, indicating that the interference by amphetamine of access of substrate to the enzyme compartment plays an important role in functional inhibition of DBH. The remainder of the effect in vesicles probably represents direct inhibition of the enzyme.
In synaptosomes, similar actions on uptake of substrate and on functional enzyme activity were noted, indicating that amphetamine‐induced inhibition of the neuronal amine pump can also affect DBH activity if the substrate is supplied exogenously.
In addition to the effects of amphetamine in vitro, chronic administration of amphetamine to rats produced an increase in total activity of adrenal DBH.
The net effect of amphetamine on DBH activity thus represents the summation of direct inhibition of the enzyme, indirect inhibition via reduced access of substrate and enhancement of activity via trans‐synaptic induction.
ONTOGENESIS OF ENZYME SYSTEMS DEAMINATING DIFFERENT MONOAMINES
Authors: BLATCHFORD D. , HOLZBAUER MARGARETHE , GRAHAME‐SMITH D.G. , YOUDIM M.B.H. 
Published: July 2012

A detailed investigation into the postnatal development of the activity of the enzyme monoamine oxidase (MAO) in the rat and domestic pig was carried out.
MAO activity was measured in littermate male rats aged between 3 and 122 days belonging to six breeding colonies. The tissues studied were three brain regions in which monoamines may play a role in neuronal transmission (septum, hypothalamus, corpus striatum) and, for comparison, in the cerebellum. Liver, heart and adrenal glands were the peripheral organs studied. The following substrates were used to measure MAO activity in each tissue homogenate: kynuramine, tyramine, dopamine, tryptamine and 5‐hydroxytryptamine (5‐HT).
MAO activity towards kynuramine, tyramine and dopamine increased after birth in all brain regions and also in the liver, to reach maximal values between days 40 and 80. In the heart and the adrenal glands enzyme activity remained low up to 30–40 days and then increased steeply. This was the case in all litters examined.
All tissues deaminated more tyramine than dopamine. In the liver, the ratio of the quantities of tyramine deaminated/dopamine deaminated was approx. 2 at all ages. In the homogenates of whole brains (including or excluding the hypothalamus and striatum) this ratio was also 2 at all ages. In contrast in the isolated striatum and hypothalamus it was first much higher and reached a value of 2 only at an age of about 20 days. This may indicate an independent development of a dopamine and a tyramine deaminating enzyme system in discrete brain regions. It was suggested, that the low ability to deaminate dopamine in discrete brain regions may be due to the local presence of an enzyme inhibitor which becomes too diluted to be active in homogenates of whole brain.
Deamination of tryptamine in the striatum decreased between day 5 and 20 in 3 out of 4 colonies tested. There was a large fall in the deamination of 5‐HT in all tissues of one group of rats, but in another 4 groups the tissues of the 5 day old rats deaminated smaller amounts of 5‐HT than those of the older rats.
Purified hypothalamic mitochondria from 40 day old rats deaminated more tyramine and dopamine but not tryptamine per mg protein than those from 5 day old rats.
In the domestic pig there was a significant rise in the values in hippocampal MAO activity towards dopamine and tyramine from the foetus (55 day gestation) to the 1 week old piglet. A further steady rise up to week 6 was indicated, but this rise was not statistically significant. The difference between rat and pig probably reflected the much higher degree of maturity of the latter at birth.
In the hippocampus of the pig the ratio between the amount of tyramine deaminated/dopamine deaminated decreased from > 10 (foetus) to 4.8 in the 6 week old pig and 2 in the adult.
UTERINE RECEPTORS FOR OXYTOCIN: CORRELATION BETWEEN ANTAGONIST POTENCY AND RECEPTOR BINDING
Authors: SOLOFF M.S. 
Published: July 2012

The apparent dissociation constants (Kd) of four competitive antagonists of oxytocin were estimated from their ability to compete with [3H]‐oxytocin for binding sites in particulate fractions from rat uterine homogenates.
These apparent Kd values were not significantly different from the Kd values calculated from the published potency of each compound as an antagonist of oxytocin‐induced uterine contractions.
These results support the conclusion that the binding sites for oxytocin are part of the receptor complex. Furthermore, ‘spare receptors' for oxytocin do not appear to be present in significant quantities, and the relative potency of each antagonist appears to depend upon its affinity for the receptor site rather than its intrinsic activity.
The antagonists used in these studies were [N‐acetyl, 2‐O‐methyltyrosine]oxytocin, [1‐(β‐mercapto‐β,β‐diethylpropionic acid)]oxytocin, [1‐(β‐mercapto‐β,β‐pentamethylenepropionic acid)]‐oxytocin, and [1‐(deaminopenicillamine), 4‐threonine]oxytocin.
THE USE OF DIFFERENT AGONISTS IN ANTAGONIST AFFINITY CONSTANT ESTIMATIONS
Authors: ROBERTS F. , STEPHENSON R.P. 
Published: July 2012

The affinities of 4 muscarinic antagonists were estimated on intact pieces of guinea‐pig ileum using the agonists carbachol and pentyl trimethylammonium both in separate experiments and in the same experiment.
The apparent affinities were slightly but consistently higher when estimated from the responses produced by pentyl trimethylammonium than when estimated from the responses produced by carbachol.
This difference was greatly reduced or abolished if totally denervated logitudinal muscle strips were used rather than intact pieces of ileum. It is therefore suggested that the difference is due to the presence of receptors in the ganglionic layer.
To explain the difference in apparent affinity of the antagonists these receptors can not be identical to the muscarinic receptors on the smooth muscle.
In addition they can not be nicotinic ganglionic receptors as the difference did not appear to be affected by the presence or absence of hexamethonium.
EFFECTS OF DRUGS AFFECTING ENDOGENOUS AMINES OR CYCLIC NUCLEOTIDES ON ETHANOL WITHDRAWAL HEAD TWITCHES IN MICE
Authors: COLLIER H.O.J. , HAMMOND M.D. , SCHNEIDER C. 
Published: July 2012

Twenty‐four hours after ethanol withdrawal, dependent mice exhibited frequent head twitching. Naive mice exhibited similar twitching 15 min after treatment with 5‐hydroxytryptophan (5‐HTP) or 6 h after α‐methyl‐p‐tyrosine (AMPT). Ethanol lessened the incidence of head twitches induced by any of these treatments. 5‐HTP and AMPT each increased the incidence of head twitches induced by withdrawal of ethanol from dependent mice.
Drugs that affect the amount or activity of endogenous amines or cyclic nucleotides modified the incidence of head twitches. Nearly all drugs acted in the same direction on twitching elicited by any of these three treatments.
The incidence was lessened by: (a) methysergide, methergoline, MA 1420, p‐chlorophenylalanine and p‐chloroamphetamine; (b) dopamine, noradrenaline, l‐DOPA, amphetamine and apomorphine; (c) hyoscine and nicotine; and (d) adenosine triphosphate, dibutyryl cyclic adenosine‐3′,5′‐monophosphate (db cyclic AMP) and prostaglandins E1 and E2.
The incidence was increased by: (a) acetylcholine, carbachol and physostigmine; and (b) guanosine triphosphate, dibutyryl cyclic guanosine monophosphate (db cyclic GMP), theophylline and 3‐isobutyl‐1‐methyl‐xanthine.
These findings suggest that head twitching induced by these three treatments arises from a common biochemical mechanism, which may ultimately be a change in favour of cyclic GMP of the balance between this nucleotide and cyclic AMP within appropriate neurones. This imbalance appears to be elicited or increased by 5‐hydroxytryptamine and acetylcholine and to be decreased by dopamine, noradrenaline and E prostaglandins.
Neither actinomycin D nor cycloheximide, given during the induction of ethanol dependence, altered the incidence of head twitches after ethanol withdrawal.
FURTHER STUDIES ON THE MODE OF ACTION OF ISOPRENALINE ON GASTRIC SECRETION IN THE CONSCIOUS RAT
Authors: LUNDELL L. , SVENSSON S.E. , NILSSON G. 
Published: July 2012

The effect of isoprenaline on gastric secretion evoked by various means has been studied in conscious rats provided with Pavlov and Heidenhain pouches.
Interdigestive acid secretion in the Pavlov pouch was reduced by isoprenaline, whereas pepsin secretion was unaltered.
Central vagal stimulation effected by 2‐deoxy‐d‐glucose injection evoked a gastric secretory response that was substantially reduced by isoprenaline.
2‐Deoxy‐d‐glucose increased the mobilization of gastric mucosal histamine, an effect that was prevented by isoprenaline.
Isoprenaline infusion alone induced a slight increase in histamine mobilization and also a considerable elevation of immunoreactive serum gastrin concentration.
The secretory response to food in the Pavlov pouch was almost abolished by isoprenaline.
Although the acid response to histamine in the Heidenhain pouch was susceptible to isoprenaline inhibition, that to methacholine was not.
Pepsin secretion in the Heidenhain pouch preparation stimulated by histamine or methacholine seemed to be enhanced by isoprenaline.