bluuebunny/crossref_metadata_2025_split huggingface dataset:
CALCIUM EFFLUX AND SECRETION OF α‐AMYLASE FROM RAT PANCREAS
Authors: HEISLER S. 
Published: July 2012

The efflux of 45Ca from rat pancreas was investigated in relation to the secretion of α‐amylase.
The 45Ca space in the pancreas was increased 1.6 times when pancreatic tissue was incubated in media in which the extracellular calcium concentration was reduced from 1.0 to 0.05 Mm.
Carbachol increased the rate of 45Ca efflux from the tissue and this effect was associated with an increase in the release of α‐amylase. Dibutyryl cyclic adenosine monophosphate (AMP) also evoked a secretory response, but did not alter the rate of 45Ca efflux. In combination with carbachol, the dibutyryl analogue of cyclic AMP reduced the carbachol‐stimulated increase in 45Ca efflux while enhancing the release of secretory protein.
The stimulatory effect of carbachol on 45Ca efflux was observed when pancreatic tissues were incubated in media containing a high concentration of ethyléneglycolbis (β‐aminoethyl)‐N,N′‐tetraacetic acid (EGTA).
Atropine blocked the effects of carbachol on both 45Ca efflux and secretion of α‐amylase.
It was concluded that intracellular calcium can and may sustain stimulus‐secretion coupling in the rat exocrine pancreas.
EFFECTS OF PROSTAGLANDIN INHIBITORS ON ANGIOTENSIN, OXYTOCIN AND PROSTAGLANDIN F2α CONTRACTILE EFFECTS ON THE RAT UTERUS DURING THE OESTROUS CYCLE
Authors: BAUDOUIN‐LEGROS MARYVONNE , MEYER P. , WORCEL M. 
Published: July 2012

In the rat isolated uterus maximal spontaneous contractions and maximal sensitivity to angiotensin II, oxytocin and prostaglandin F2α were observed in di‐ and proestrus. Minimal sensitivity to the three agonists was observed in metoestrus. Maximal contractile effects of angiotensin II, oxytocin and prostaglandin F2α were thus observed when the ratio oestrogen/ progesterone levels was high.
The oestrogen‐dependent sensitivity of the rat uterus is partially mediated by endogenous prostaglandins. Indomethacin suppressed the increased sensitivity to angiotensin and oxytocin present in dioestrus and proestrus but did not affect that to prostaglandin F2α. Polyphloretin phosphate at a concentration of 10μg/ml resulted in complete identity of dioestrus and metoestrus dose‐response curves to angiotensin and oxytocin.
Spontaneous uterine contractions observed when oestrogen levels are high are also dependent on intramural prostaglandins as they were inhibited by indomethacin and polyphloretin phosphate. In the metoestrus uterus, prostaglandin F2α induced the reappearance of spontaneous contractions.
Prostaglandin F2α had a potentiating effect on angiotensin‐elicited contractions which persisted after washing out prostaglandin F2α.
FURTHER STUDIES ON THE MODE OF ACTION OF PSYCHOTOMIMETIC DRUGS: ANTAGONISM OF THE EXCITATORY ACTIONS OF 5‐HYDROXYTRYPTAMINE BY METHYLATED DERIVATIVES OF TRYPTAMINE
Authors: BRADLEY P.B. , BRIGGS I. 
Published: July 2012

The actions of 5‐methoxytryptamine (5‐MeOT), N,N‐dimethyltryptamine (DMT), 5‐hydroxy‐N,N‐dimethyltryptamine (bufotenine, 5‐HODMT) and 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeODMT), and their interactions with 5‐hydroxytryptamine (5‐HT), acetylcholine, (–)‐noradrenaline, and glutamate were studied by microiontophoresis on single neurones in the brain stem of rats anaesthetized with urethane or decerebrate cats.
Like d‐lysergic acid diethylamide (LSD 25) the three psychotomimetic derivatives (DMT, 5‐HODMT, 5‐MeODMT) specifically antagonized 5‐HT excitations of single neurones, but the non‐psychotomimetic 5‐MeOT had no antagonistic effects.
In contrast to LSD 25, the psychotomimetic tryptamines only rarely antagonized glutamate effects, indicating that the excitatory 5‐HT receptors and the glutamate receptors on the same neurones may be closely related spatially, but are separate.
The methylated tryptamine derivatives were able to mimic the actions of 5‐HT on neurones. The non‐psychotomimetic 5‐MeOT was most potent in this respect, while the other three derivatives which are psychotomimetic, were less active.
The 5‐HT mimicking actions of 5‐MeOT were the same in rats pretreated with p‐chlorophenylalanine or reserpine as in untreated rats. It therefore seems that the 5‐HT mimicking actions are unlikely to be due to release of 5‐HT, but are due to direct actions on 5‐HT receptors.
The evidence presented supports the hypothesis that LSD‐like psychotomimetics act by an antagonism of 5‐HT in the lower brain stem, and is not compatible with the suggestion that the psychotomimetic action of these drugs is related to 5‐HT receptor stimulation.
BIOASSAY OF OXYTOCIN ON THE SUPERFUSED MAMMARY GLAND OF THE MOUSE, USING AN AUTOMATIC APPARATUS
Authors: ROBINSON I.C.A.F. , WALKER J.M. 
Published: July 2012

A sensitive method of assaying oxytocin using the superfused mouse mammary gland is described. The method is shown to be reliable, accurate and precise. Assays are performed automatically and the preparation is stable for at least 18 hours.
The preparation is relatively insensitive to bradykinin, histamine, 5‐hydroxytryptamine, angiotensin, prostaglandin F2α, adrenaline and noradrenaline. The contractions produced by acetylcholine can be abolished by atropine without the sensitivity to oxytocin being affected.
Vasopressin has a variable activity on the preparation; its potency can be as high as one‐fifth that of oxytocin.
It is concluded that this method compares favourably with other published methods.
THE HAEMODYNAMIC EFFECTS OF PROLONGED ORAL ADMINISTRATION OF OXYFEDRINE, A PARTIAL AGONIST AT β‐ADRENOCEPTORS: COMPARISON WITH PROPRANOLOL
Authors: PARRATT J.R. 
Published: July 2012

Haemodynamic changes have been studied in cats after the chronic oral administration of oxyfedrine (14 mg/kg for 3–4 weeks) or of placebo (lactose). The initial part of the study was carried out under double‐blind conditions. The arterial blood pressure was between 19 mmHg (diastolic) and 27 mmHg (systolic) higher in the oxyfedrine treated animals, but there were no differences between the two groups with regard to cardiac output, left ventricular dP/dt max, heart rate or systolic ejection time.In cats similarly treated with propranolol (4 mg/kg) there was a slight (12%), but significant, reduction in cardiac output.Isoprenaline dose‐response curves were shifted to the right in the cats administered oxyfedrine as well as in those administered propranolol. The degree of shift was five‐fold (positive chronotropic response) and 20‐fold (decrease in diastolic blood pressure) in the oxyfedrine group and 10‐ and 80‐fold, respectively, in the propranolol group.In contrast to the partial blockade of the effects of isoprenaline, the haemodynamic response to oxyfedrine was largely unaltered, both in the cats pretreated with propranolol and in those pretreated with oxyfedrine. The pressor response to noradrenaline was potentiated in the cats pretreated with oxyfedrine.These results provide an explanation for the anti‐anginal action of oxyfedrine. Some degree of β‐adrenoceptor blockade is achieved without a reduction in cardiac output or left ventricular dP/dt max. The relevance of these findings to the haemodynamic situation in angina is discussed.
THE EFFECTS OF A NEW β‐ADRENOCEPTOR BLOCKING COMPOUND, TOLAMOLOL, ON HAEMODYNAMICS AND MYOCARDIAL FUNCTION IN MAN
Authors: HILLIS W.S. , HUTTON I. , LAWRIE T.D.V. , LORIMER A.R. , REID J.M. 
Published: July 2012

The effects of tolamolol on haemodynamics and myocardial contractility were investigated in two groups of six patients undergoing diagnostic cardiac catheterization.
The intravenous administration of tolamolol (0.15 mg/kg) produced a significant fall in heart rate from a control value (87 ± 7 to 62 ± 3 beats/min) 5 min after administration and a concomitant fall in cardiac output from 4.7 ± 0.9 to 3.5 ± 0.8 litres/minute. There was no significant change in systemic blood pressure, pulmonary artery blood pressure or stroke volume.
There was no change in left ventricular end diastolic pressure after tolamolol. There was a fall in the maximum rate of rise of the left ventricular pressure (LV dp/dtmax) and the derived index of the left ventricular contractile state (Vmax).
These results suggest that tolamolol has a predominantly negative chronotropic but also a lesser negative inotropic action on the heart.
THE ACTION OF 5‐HYDROXYTRYPTAMINE AND RELATED COMPOUNDS ON THE ACTIVITY OF RETZIUS CELLS OF THE LEECH Hirudo medicinalis
Authors: SMITH P.A. , WALKER R.J. 
Published: July 2012

The equipotent molar ratios of a range of tryptamine analogues, as compared with 5‐hydroxytryptamine (5‐HT), have been determined on the basis of their ability to hyperpolarize the membrane potential of the Retzius cell of the leech, Hirudo medicinalis.
The substitution of methyl, fluoro, chloro, methoxy or acetyl groups onto the 5‐HT molecule progressively reduced the potency.
5‐Methoxylation or terminal N‐methylation of tryptamine considerably increased the potency of tryptamine but these compounds tended to depolarize cells rather than cause hyperpolarization. In some experiments they were ineffective on preparations pretreated with 5‐HT.
It is suggested that these compounds may act by a different mechanism from the 5‐hydroxylated indoles, perhaps involving a different receptor.
ROLE OF ENDOGENOUS CATECHOLAMINES IN THE ANTI‐INFLAMMATORY ACTIVITY OF α‐ADRENOCEPTOR BLOCKING AGENTS
Authors: GREEN K.L. 
Published: July 2012

Drugs which release or modify the response to catecholamines were examined for their effect on the permeability of the mouse peritoneal vascular bed to circulating plasma albumin, labelled with Evans blue.
Phenoxybenzamine, phentolamine, piperoxane, yohimbine or cocaine reduced the extravasation of Evans blue into the peritoneum, an effect which was antagonized by β‐adrenoceptor blocking drugs. The inhibitory effect of desipramine on the extravasation of Evans blue was less completely antagonized by β‐adrenoceptor blockade.
Inhibition of catecholamine biosynthesis, ganglion blockade or adrenergic neurone blockade antagonized the reduction in dye extravasation by α‐adrenoceptor blocking agents and cocaine, but had no significant effect on the response to desipramine. The inhibitory effects of α‐adrenoceptor blocking agents on dye extravasation were not prevented by bilateral adrenalectomy.
Mice subjected to the procedure for estimation of vascular permeability excreted increased amounts of adrenaline and noradrenaline. Pretreatment with phenoxybenzamine, piperoxane or cocaine further increased catecholamine excretion, but desipramine caused only a small increase in catecholamine excretion which did not correlate with its effect on dye extravasation.
It is suggested that phenoxybenzamine, phentolamine, piperoxane and cocaine reduce vascular permeability in the mouse peritoneum by releasing and/or potentiating the effects of endogenous catecholamines on β‐adrenoceptors. Endogenous catecholamines do not appear to be involved in the anti‐inflammatory activity of desipramine.
THE PHARMACOKINETICS OF [14C]‐EDROPHONIUM IN NORMAL WISTAR RATS AND HOMOZYGOUS GUNN RATS WITH LIGATED RENAL PEDICLES
Authors: BACK D.J. , CALVEY T.N. 
Published: July 2012

The distribution kinetics of [14C]‐edrophonium were studied in both normal Wistar and homozygous Gunn rats with ligated renal pedicles.
After intravenous injection the plasma concentration‐time curve of [14C]‐edrophonium was adequately fitted by a triexponential function in both species of rat and interpreted in terms of a three compartment model.
The influence of the route of administration (i.e., systemic venous versus hepatic portal) of [14C]‐edrophonium on its concentration in plasma was studied in normal Wistar rats with ligated renal pedicles. There was a marked difference in the area under the plasma concentration‐time curve depending on the route of administration.
The parameters of the model were determined and compared.
The value of the metabolism rate constant was approximately the same in both species of rat. This suggests that the rate of conjugation of [14C]‐edrophonium is unaltered in the homozygous Gunn rat despite the genetic lesion in UDP‐glucuronyltransferase.
THE EFFECTS OF MICROIONTOPHORETICALLY APPLIED MORPHINE AND TRANSMITTER SUBSTANCES IN RATS DURING CHRONIC TREATMENT AND AFTER WITHDRAWAL FROM MORPHINE
Authors: BRADLEY P.B. , DRAY A. 
Published: July 2012

The effects of microiontophoretically applied acetylcholine, noradrenaline, 5‐hydroxytryptamine and morphine were studied on single brain stem neurones of rats during chronic morphine pretreatment and 24 h after its withdrawal. No significant changes were observed in the initial spontaneous neuronal firing rate or in the qualitative or quantitative effects of acetylcholine, noradrenaline or 5‐hydroxytryptamine. However, in chronically treated animals there was a significant decrease in the number of neurones excited by morphine or showing tachyphylaxis to morphine on repeated microiontophoretic applications.We suggest that some of the cellular central nervous system changes which occur during chronic morphine treatment are reflected by the decrease in sensitivity of neurones to morphine excitation.
STUDIES ON THE METABOLISM OF CATECHOLAMINES IN THE CENTRAL NERVOUS SYSTEM OF THE MOUSE
Authors: CEASAR P.M. , HAGUE P. , SHARMAN D.F. , WERDINIUS B. 
Published: July 2012

The distribution of the metabolites of noradrenaline, 1‐(3,4‐dihydroxyphenyl)ethane‐1,2‐diol (DOPEG) and 1‐(4‐hydroxy‐3‐methoxyphenyl)ethane‐1,2‐diol (MOPEG), in the brain of the mouse has been investigated.
The rate of disappearance of the metabolites after inhibition of the enzyme monoamine oxidase has been used to estimate their turnover rates in the mouse hypothalamus. It was concluded that the turnover of DOPEG was much faster than that of MOPEG.
When mice were treated with reserpine dissolved in 5% ascorbic acid solution there was an increase in the hypothalamic concentration of both MOPEG and DOPEG. However, similar increases in the concentrations of the two metabolites were seen when the animals were treated with 5% ascorbic acid solution alone.
The administration of tropolone, an inhibitor of the enzyme catechol‐O‐methyl transferase, resulted in an increase in the concentration of DOPEG.
Mice, exposed to a temperature of −15° C showed increased hypothalamic concentrations of both DOPEG and MOPEG.
The rates of formation in the mouse striatum of 3,4‐dihydroxyphenylacetic acid (DOPAC) and 4‐hydroxy‐3‐methoxyphenylacetic acid (HVA), acidic metabolites of dopamine, were compared with the turnover rate of dopamine, estimated from the rate at which this catecholamine disappears after treatment with α‐methyl‐p‐tyrosine. It was concluded that the estimate of dopamine turnover obtained by this method is likely to be too large because of the compensatory feedback mechanism which is thought to play a role in the metabolism of dopamine in the brain.
THE RELATION BETWEEN THE ADRENERGIC NEURONE‐BLOCKING AND NORADRENALINE‐DEPLETING ACTIONS OF SOME GUANIDINE DERIVATIVES
Authors: ABBS E.T. , DODD M.G. 
Published: July 2012

The effects of some guanidine derivatives, (—)‐N‐(1‐phenylethyl) guanidine (PEG), guanethidine and debrisoquine have been investigated on the content and subcellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline from this organ during stimulation of the splenic nerve.
PEG and guanethidine, at a dose of 5 mg/kg, produced adrenergic neurone blockade within 15 min and the same dose of debrisoquine produced blockade within 30 minutes.
All three compounds produced a decrease of similar magnitude in the noradrenaline content of the high‐speed particulate (P2) and supernatant (S) fractions of splenic homogenates; these actions were temporally correlated with the adrenergic neurone‐blocking action of the compounds.
PEG did not produce any further decrease in the noradrenaline content of the subcellular fractions at times up to 18 h after its administration; adrenergic neurone blockade was maintained throughout this period but had disappeared after 7 days when the noradrenaline content of the subcellular fractions was restored to control levels.
Guanethidine, in contrast, caused a marked progressive loss of the transmitter from all subcellular fractions‐an effect which was maximal 18 h after its administration but continued, as did the adrenergic neurone‐blocking action, for at least 72 hours. This additional loss of noradrenaline, over and above that seen after 15 min, is unlikely to be connected with the adrenergic neurone‐blocking action of the drug.
Dexamphetamine both prevented and antagonized the neurone blockade and the subcellular noradrenaline‐depleting action of PEG and guanethidine. The restoration of nerve function after administration of dexamphetamine to animals pretreated with 5 mg/kg of either of these compounds was temporally correlated with a selective repletion of the noradrenaline content of the supernatant fraction of the spleen.
Larger doses (15 mg/kg) of PEG or guanethidine produced a selective depletion of noradrenaline in only the supernatant fraction of the spleen. This depletion was temporally correlated with the adrenergic neurone‐blocking action of these compounds. The lack of effect of the compounds at this dose level on the noradrenaline contained in the P2 fraction may be due to ‘stabilization’ of the store of noradrenaline in vivo which gives rise to this fraction on homogenization.
It is suggested that the guanidine‐type adrenergic neurone‐blocking agents displace the noradrenaline which is readily available for release by nerve impulses, and that it is this action that may account for their sympathomimetic properties.
The ability of these guanidines to impair the release of noradrenaline by nerve impulses could occur because whilst they are present within the neurone the ‘nerve‐releasable store’, which may in these experiments appear in the supernatant fraction after homogenization, may be unable to refill with transmitter.
LACK OF COPULATORY BEHAVIOUR IN MALE CASTRATED RATS AFTER p‐CHLOROPHENYLALANINE
Authors: DEL FIACCO M. , FRATTA W. , GESSA G.L. , TAGLIAMONTE A. 
Published: July 2012

The effect of p‐chlorophenylalanine (PCPA) on the copulatory behaviour of normal and castrated male rats with females in oestrus was studied.
Castration 2 months before the experiment completely prevented the increased copulatory behaviour produced by PCPA in normal rats.
The administration of testosterone restored the copulatory behaviour in the castrated rats indicating that testosterone is essential for this behaviour.
ON THE SIMULTANEOUS ACTION OF TWO COMPETITIVE ANTAGONISTS
Authors: GINSBORG B.L. , STEPHENSON R.P. 
Published: July 2012

A hypothesis is outlined predicting the conditions in which the addition of a second competitive antagonist will increase rather than reduce the response to an agonist.
Experiments were performed with the guinea‐pig ileum as the test tissue, hexyltrimethyl ammonium as the agonist, benzilyltropine methiodide as the ‘slow’ antagonist and pentyltriethyl ammonium as the ‘fast’ antagonist.
The results are consistent with the hypothesis, if the affinity constant for hexyltrimethyl ammonium is between 2.7 and 3.7 × 104 m−1, if the dissociation time constant for the slow antagonist is greater than 10 min and if that for the fast antagonist is less than 10 seconds.
THE LONG‐TERM REGULATION OF TYROSINE HYDROXYLASE ACTIVITY IN CULTURED SYMPATHETIC GANGLIA: ROLE OF GANGLIONIC NORADRENALINE CONTENT
Authors: MACKAY A.V.P. 
Published: July 2012

An organ culture system is described for the in vitro maintenance of superior cervical sympathetic ganglia taken from mice of any age. The relation of tyrosine hydroxylase (T‐OH) activity to ganglionic noradrenaline (NA) content has been investigated under various culture conditions.
Depolarizing stimuli such as raised extracellular potassium and ouabain evoked increases of approximately 70% in the T‐OH activity of cultured ganglia over a 48 h period. Exposure to a high concentration of potassium (high K+) for 30 min at the start of a 48 h culture was sufficient to elicit significant increases in T‐OH activity.
Depolarization‐induced rises in T‐OH activity were observed after culture in the presence or absence of nerve growth factor.
The NA content of ganglia, cultured for 48 h in the presence of high K+, ouabain, reserpine, clorgyline and α‐methyl‐p‐tyrosine, showed no constant relation to their T‐OH activity.
Dibutyryl cyclic adenosine 3′‐5′‐monophosphate (dibutyryl cyclic AMP) mimicked high K+ in its effect on ganglionic T‐OH activity and NA content. Theophylline enhanced the potassium effects.
Rises in the T‐OH activity of ganglia cultured in the presence of high K+ and dibutyryl cyclic AMP were abolished if the protein synthesis inhibitors cycloheximide or actinomycin D were present in the culture medium.
It is concluded that the link between prolonged depolarization and rises in T‐OH activity does not seem to depend upon changes in ganglionic NA content. In the intact animals, trans‐synaptic modulation may take the form of a depolarization‐induced rise in the cyclic AMP content of sympathetic ganglionic neurones leading to nuclear mediated synthesis of T‐OH.
EFFECT OF PREGANGLIONIC NERVE STIMULATION ON SENSITIVITY OF THE SUPERIOR CERVICAL GANGLION TO NICOTINIC BLOCKING AGENTS
Authors: ALKADHI K.A. , McISAAC R.J. 
Published: July 2012

Periodic stimulation (every 10 min) of the cervical sympathetic nerve increased the ganglionic block by low concentrations of chlorisondamine (CHL) in the superior cervical ganglion of the cat when compared to the contralateral unstimulated side.
Periodic stimulation of the postganglionic nerve was ineffective in increasing the block.
Ganglionic block by low concentrations of mecamylamine had the same stimulus dependency, but ganglionic block by any dose of hexamethonium was not influenced by nerve stimulation.
Physostigmine infused together with CHL increased the rate of onset of block produced by CHL. Atropine had no apparent effect on the development of ganglionic block by CHL.
Repeated intra‐arterial injections of 1,1‐dimethyl‐4‐phenylpiperazinium into the circulation of the superior cervical ganglion increased the magnitude of block produced by CHL. Similar injections of methacholine had no effect on ganglionic block produced by CHL.
The results are interpreted to indicate that activation of ganglionic nicotinic receptors increased the affinity of receptors for CHL and mecamylamine.
THE ROLE OF BRAIN 5‐HYDROXYTRYPTAMINE IN THE HYPERACTIVITY PRODUCED IN RATS BY LITHIUM AND MONOAMINE OXIDASE INHIBITION
Authors: GRAHAME‐SMITH D.G. , GREEN A.R. 
Published: July 2012

Administration to rats of LiCl (3 mEq/kg) subcutaneously twice daily for 3 days followed by monoamine oxidase inhibition with either tranylcypromine (TCP; 20 mg/kg) or pargyline (75 mg/kg) on the fourth day produces a syndrome of hyperactivity indistinguishable from that produced by monoamine oxidase inhibition and l‐tryptophan administration.
At least 3 injections of LiCl (3 mEq/kg) are necessary before hyperactivity is seen but one dose of LiCl (10 mEq/kg) 5 h before TCP also caused hyperactivity. The hyperactivity is blocked by prior administration of p‐chlorophenylalanine, a tryptophan hydroxylase inhibitor.
LiCl pretreatment does not alter the concentration of l‐tryptophan in the brain. However after monoamine oxidase inhibition the 5‐hydroxytryptamine (5‐HT) accumulation was significantly greater in animals given lithium indicating an increase in 5‐HT synthesis of 70%. This was confirmed by measuring 5‐hydroxyindoleacetic acid accumulation after probenecid (200 mg/kg).
The hyperactivity produced by the 5‐HT analogue, 5‐methoxy N,N‐dimethyltryptamine was not potentiated by lithium pretreatment but one injection of LiCl (3 mEq/kg) which did not alter the rate of 5‐HT synthesis, did potentiate the hyperactivity following TCP (20 mg/kg) and l‐tryptophan (50 mg/kg).
These results suggest that lithium administration may cause an initial alteration of the 5‐HT available for release at the nerve ending, which is followed after subsequent treatment by an increase in the rate of 5‐HT synthesis. The possible clinical significance of these findings is discussed.