bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the mechanism of action of some ganglion‐blocking drugs in the rabbit superior cervical ganglion
Authors: LEES G. M. , NISHI S. 
Published: July 2012

Summary
. Mechanisms of action of hexamethonium, mecamylamine and (+)‐tubocurarine on the rabbit superior cervical ganglion were investigated by intracellular recording techniques.
. In concentrations up to 1 mm, none of these drugs affected the resting membrane potential nor altered the excitability of the postganglionic neurone to direct or antidromic stimulation.
. Post‐tetanic potentiation of the excitatory postsynaptic potential (e.p.s.p.) was inhibited by mecamylamine (10–100 μm) but not affected by either hexamethonium (5–100 μm) or (+)‐tubocurarine (10–50 μm).
. The decline in amplitude of successive e.p.s.ps in a train (40 Hz) was not influenced by hexamethonium or (+)‐tubocurarine but was greatly exaggerated in the presence of mecamylamine; desensitization of the receptors for acetylcholine was excluded as a possible explanation for this latter finding.
. Mecamylamine depressed the quantal content of e.p.s.ps in a train, with the exception of the first e.p.s.p. which had an increased quantal content.
. Reduction in quantal content was attributed to a substantial fall in the size of the store of quanta of transmitter immediately available for release and to a reduction in the rate of mobilization of acetylcholine into that store; mecamylamine also caused a simultaneous increase in the fractional release.
. Hexamethonium and (+)‐tubocurarine had no effect on transmitter release.
. The time‐course of presynaptic effects of mecamylamine was similar to the duration of its postsynaptic blocking action.
. It is concluded that inhibition of ganglionic transmission by mecamylamine is due to both presynaptic and postsynaptic inhibitory actions; in contrast, hexamethonium and (+)‐tubocurarine reduce transmission solely by their postsynaptic actions.
Inhibitory and stimulatory effects of secretin on gastric secretion in conscious rats
Authors: JOHANSSON IRENE , LUNDELL L. , SVENSSON S. E. 
Published: July 2012

Summary
. The effect of pure secretin on gastrin‐induced secretion has been studied in conscious rats with Pavlov or Heidenhain pouches.
. Rapid intravenous injection of secretin did not inhibit a plateau secretion of acid in the Heidenhain pouch, but infusion of the same amount of secretin over two hours inhibited secretion in both Heidenhain and Pavlov pouches.
. A rapid intravenous injection of secretin before the onset of gastrin infusion enhanced the acid secretory response to gastrin in both types of pouches.
. Secretin stimulated pepsin secretion.
Effect of etorphine, morphine and diprenorphine on neurones of the cerebral cortex and spinal cord of the rat
Authors: BISCOE T. J. , DUGGAN A. W. , LODGE D. 
Published: July 2012

Summary
. The actions of etorphine, morphine and diprenorphine were investigated on neurones of the cerebral cortex and spinal cord of rats anaesthetized with pentobarbitone.
. In the cerebral cortex, intravenous etorphine increased the latency of the primary evoked response to a peripheral nerve stimulus and suppressed the rhythmical after‐discharge. Diprenorphine reversed this effect. These actions were demonstrated on both field potentials and unit firing.
. Morphine had no effect on the primary response but the frequency of after‐discharge bursts was reduced and there was an increase in firing between bursts.
. In the cerebral cortex, electrophoretically applied etorphine reduced after‐discharges when applied for long periods but had no effect on the depressant actions of glycine and γ‐aminobutyric acid (GABA) nor on the excitant action of acetylcholine and l‐glutamate. Similarly there was no alteration by etorphine of the effects of glycine, GABA and l‐glutamate on spinal cord neurones.
. It is concluded that etorphine may act pre‐synaptically in the cerebral cortex.
The nature of adrenergic mechanisms involved in anaphylatoxin activity in the guinea‐pig
Authors: HICKS R. , SACKEYFIO A. C. 
Published: July 2012

Summary
. Evidence is presented to elucidate the nature of the adrenergic mechanisms involved in responses of the guinea‐pig to anaphylatoxin (AT).
. Investigation by means of adrenalectomy, adrenergic neurone blockade, α‐ and β‐ adrenoceptor blockade and exclusion of autonomic reflexes, revealed that the adrenergic mechanisms provoked included catecholamine release from the adrenal medulla, sympathetic reflex activity, stimulation of adrenergic neurones and α‐ and β‐adrenoceptor activity.
. The cardiovascular effects of AT, mediated by histamine release, were largely attributable to adrenal medullary and adrenergic neuronal mechanisms. These mechanisms also exerted a restraint on the predominantly histamine mediated bronchoconstrictor effect of AT.
. The cardiovascular effects of AT activity, not attributable to histamine release, were also probably associated with catecholamine release. However, the bronchoconstrictor component of this AT activity was not significantly affected by guanethidine, and it would, therefore, appear that neuronal bronchodilator mechanisms did not exert a restraint upon this aspect of AT activity.
. These findings are generally compatible with previous work showing that adrenergic mechanisms operate during AT‐induced responses. In contrast to previous reports, however, the adrenergic activity was predominantly associated with the effects of released histamine.
Histamine formation from 14C‐l‐histidine in man
Authors: BERG B. , GRANERUS G. , JOHANSSON MAJ‐BRITT , WESTLING H. , WHITE T. 
Published: July 2012

Summary
. 14C‐l‐histidine was given i.v. to one normal subject and two patients with chronic myelocytic leukaemia. Urinary excretion of histamine and two of its metabolites methylhistamine and methylimidazoleacetic acid, total as well as 14C‐labelled, was measured, as well as blood 14C‐histamine. In addition the total urinary and pulmonary elimination of 14C was followed.
. Total 14C elimination was high during the first days, then declined slowly except for a plateau at the 10th–14th day in the two patients. There was a measurable elimination even after some months.
. 14C‐histamine appeared in the blood of the leukaemic patient, whereas in the normal subjects the values were hardly measurable.
. The leukaemic patients excreted much more of the two 14C‐labelled histamine metabolites than the normal subject. The difference in excretion of the 14C‐labelled metabolites was largest around the 12th day after the infusion of 14C‐l‐histidine.
. The results indicate that the leukaemic patients formed at least 20 times more histamine daily than the normal subject.
Effect on reproductive organs of three clomiphene analogues
Authors: BASU J. 
Published: July 2012

Summary
. The oestrogenic properties of four triphenylethylene compounds were compared. They can be listed as follows in order of their oestrogenic potency: 1‐[p‐(β‐diethylaminoethoxy)‐phenyl]‐2‐nitro‐1,2‐diphenylethylene (E.I.P.W. 111) > clomiphene > 1‐[p‐(β‐dimethylaminoethoxy)‐phenyl]‐2‐nitro‐1,2‐diphenylethylene (E.I.P.W. 113)>1‐[p‐(β‐diethylaminoethoxy)‐phenyl]‐1,2‐diphenylethylene (E.I.P.W. 103). The oestrogenic potency of compound E.I.P.W. 111 was found to be about 1/10th of that of oestradiol.
. Compound E.I.P.W. 111 is partially antioestrogenic but not progesteronic in nature. It has no androgenic effect.
The cardiovascular actions of WR‐149,024 (1,18‐diamino‐7,13‐diaza‐9,10‐dithiaoctadecane tetrahydrochloride)
Authors: CALDWELL R. W. , HEIFFER M. H. , HERMAN E. H. 
Published: July 2012

Summary
. The general cardiovascular properties of WR‐149,024 (a straight chain sulphur‐containing aliphatic amine) in dogs and cats are reported.
. Intravenous administration of this compound produced an immediate hypotension and bradycardia in intact anaesthetized dogs. These effects were independent of the parasympathetic nervous system since they were also present in atropinized and bilaterally vagotomized dogs.
. Ascending aortic blood flow increased after administration of WR‐149,024 despite a reduction in blood pressure, contractile force and heart rate. It appears that the initial hypotension is due to a decrease in total peripheral vascular resistance since WR‐149,024 produced relatively little change in force of contraction or heart rate in the isolated, blood‐perfused heart preparation.
. WR‐149,024 reversed the pressor effects of adrenaline within 10 min of injection while at the same time the vasopressor response to angiotensin or the vasodepressor response to isoprenaline was not altered. α‐Adrenoceptor blockade was still evident up to five days after dosing.
. WR‐149,024 did not block phenylephrine inhibition of intestinal motility. These findings suggest that WR‐149,024 initiates a relatively specific and prolonged α‐adrenoceptor blockade.
Effect of chronic drug treatment on intestinal membrane transport of 14C‐l‐DOPA
Authors: RIVERA‐CALIMLIM LEONOR 
Published: July 2012

Summary
. By the use of the everted jejunal sac it was shown that chronic oral treatment of rats with various drugs can either increase or decrease the mucosal transport of 14C‐l‐DOPA or alter its serosal/tissue ratio.
. 14C‐l‐DOPA transport was significantly increased in rats that were chronically treated with l‐DOPA and diminished in those that were treated with chlorpromazine and phenobarbitone.
. Chronic treatment with amantadine and neomycin did not affect 14C‐l‐DOPA intestinal transport, although direct addition of amantadine to the medium, significantly increased 14C‐l‐DOPA transport in everted sacs of non‐treated rats. Addition of neomycin directly to the medium did not affect 14C‐l‐DOPA transport.
. The possible mechanisms of these findings and their clinical significance are discussed.
Effects of gamma‐hydroxybutyrate on chick behaviour, electrocortical activity and crossed extensor reflexes
Authors: OSUIDE GABRIEL 
Published: July 2012

Summary
Convulsant and anticonvulsant effects of gamma‐hydroxybutyrate (GHB) have been studied in chicks.
When administered alone, GHB produced weak myoclonic seizures accompanied by electrocortical synchrony and spikes.
GHB was found to protect chicks against leptazol‐ and picrotoxin‐induced seizures. A slight potentiation of strychnine‐induced seizures was evident.
Central cholinergic and adrenergic mechanisms in the release of antidiuretic hormone
Authors: BHARGAVA K. P. , KULSHRESTHA V. K. , SRIVASTAVA Y. P. 
Published: July 2012

Summary
Studies on the urine outflow, blood ADH concentration and electrolyte excretion were carried out in α‐chloralose anaesthetized hydrated dogs; the agonists and antagonists of specific cholinoceptors and adrenoceptors were injected by the intracerebroventricular technique, to delineate the role of the C.N.S. receptors in the control of ADH secretion.
Central injection of acetylcholine elicited a dose‐dependent antidiuretic response which was associated with an increase in the blood ADH titre. Central atropinization partially blocked the antidiuretic response. The remaining antidiuretic response was reversed to a diuretic one by further pretreatment with phenoxybenzamine. The diuretic response thus obtained could be blocked by propranolol.
The α‐adrenoceptor agonists, phenylephrine and noradrenaline, induced dose‐dependent antidiuretic responses with a concomitant rise in blood ADH concentration. Their effect could be blocked by pretreatment centrally with phenoxybenzamine. Low doses of adrenaline induced a diuretic response and a decrease in blood ADH concentration, higher doses elicited a dose‐dependent antidiuretic response and increase in the titre of ADH in blood. Central phenoxybenzamine pretreatment reversed the antidiuretic effect of high doses of adrenaline to a diuretic effect which could be blocked by propranolol.
Isoprenaline elicited a dose‐dependent diuretic response and a decrease in blood ADH titre and propranolol competitively blocked the effect of isoprenaline.
It is concluded that central muscarinic cholinoceptors and the α‐adrenoceptors are concerned in the release of ADH, whereas the β‐adrenoceptors are concerned with inhibition of ADH release.
The actions of prostaglandins E1 and F2α on the perfused vessels of the isolated rabbit ear
Authors: TAI SUHAILA A. AL , GRAHAM J. D. P. 
Published: July 2012

Summary
In the isolated rabbit ear vascular bed, perfused with Krebs solution, prostaglandins E1 and F2α produce dose‐dependent, phentolamine‐sensitive constrictions.
These are absent if the animal is pre‐treated with reserpine or if the ear is denervated in advance.
If noradrenaline or vasopressin is added to the Krebs solution, vascular resistance is high and PGE1 and PGF2α produce vasodilatation which is unaffected by hyoscine or propranolol.
Perfusion with theophylline, with added ATP, ADP or 3′5′‐AMP, or pre‐treatment of the animal with stilboestrol antagonizes the dilator response to PGE1 in the presence of noradrenaline, which may be reversed. Most of the responses to PGF2α are reversed. These treatments elevate the level of 3′5′‐AMP in tissues.
It is postulated that prostaglandins exert a regulatory action on 3′5′‐AMP levels through inhibition of adenyl cyclase and/or phosphodiesterase and that the resulting rising or falling level of 3′5′‐AMP determines the nature of the response by the smooth muscle to the released noradrenaline.
The effect of 2,4‐dinitrophenol on electrical and mechanical activity, metabolism and ion movements in guinea‐pig ventricular muscle
Authors: McDONALD T. F. , MacLEOD D. P. 
Published: July 2012

Summary
DNP (2,4‐dinitrophenol) reduced the duration of the action potential of guinea‐pig ventricular muscle at a greater rate than did anoxia. The effect was dose‐dependent and was modified by the concentration of glucose in the medium. DNP (0·1 mm) reduced the amplitude of the action potential of muscles incubated with 5 mm glucose; on raising the glucose concentration to 50 mm the effect was reversed.
A large dose‐dependent loss of K+ occurred within 15 min of incubation with DNP and was attributed to increased efflux. K+ loss was not related to Na+ gain during the first 60 min of incubation; during the first 30 min DNP‐treated muscle did not gain any Na+. Although the shortening of the action potential by DNP during aerobic incubation was similar to that of muscles incubated under anaerobic conditions in glucose‐free medium, the anaerobic incubation was not associated with increased 42K efflux.
It was concluded that the reduction in duration of the action potential was not necessarily the result of an increased K+ efflux. The effect of DNP on 42K efflux is considered to result from a direct effect on the cell membrane; the effect on electrical activity may be a combination of the increase in K+ efflux and a reduction in the inward current due to Na+ and Ca++ previously assumed to be dependent on the glycolytic production of ATP.
Electrogenic Na+ pumping may contribute to the maintenance of resting potential in K+‐depleted, DNP‐treated cardiac muscle.
The effect of dehydroemetine on isolated guinea‐pig atria
Authors: DUROTOYE A. O. , SALAKO L. A. 
Published: July 2012

Summary
The mechanism of the inhibitory effect of dehydroemetine on the heart was investigated using spontaneously contracting isolated guinea‐pig atria.
In normal Locke solution, dehydroemetine caused a reduction in the rate and amplitude of contraction of the atria. The effect was antagonized by adrenaline and augmented by acetylcholine.
Increasing the potassium concentration of the bathing medium increased the inhibitory effect of dehydroemetine on the atria, while decreasing the potassium concentration antagonized the effect of dehydroemetine.
The character of the inhibitory effect of dehydroemetine on the atria altered when the sodium concentration of the bathing solution was lowered to 75·6 mmol. In the normal sodium medium arrest of beat by dehydroemetine was gradual; in the low sodium medium, it was abrupt.
In the low, as in the normal sodium medium, the inhibitory effect of dehydroemetine was more marked the higher the potassium concentration of the bathing medium.
In both standard Locke solution and Locke solution containing 75·6 mmol sodium, the effect of dehydroemetine closely mimicked that obtained by adding excess potassium to the solution.
On the basis of the foregoing it was suggested that dehydroemetine acts by increasing the permeability of the myocardial cell membrane to potassium thereby leading to the accumulation of potassium in the extracellular space.
Studies of the interaction of 5‐hydroxytryptamine and the perivascular innervation of the guinea‐pig caecum
Authors: DRAKONTIDES ANNA B. , GERSHON MICHAEL D. 
Published: July 2012

Summary
The action and interaction of noradrenaline (NA), 5‐hydroxytryptamine (5‐HT) and the sympathetic innervation was studied in the isolated taenia of the guinea‐pig caecum.
Addition of 5‐HT led to a contraction of the taenia while addition of NA or perivascular nerve stimulation resulted in relaxation. Responses to 5‐HT or perivascular nerve stimulation were abolished by tetrodotoxin. Tetrodotoxin did not affect responses to applied NA. Hexamethonium and hyoscine converted the 5‐HT response to a relaxation and augmented the relaxation which followed low frequency perivascular nerve stimulation. Hexamethonium and hyoscine did not affect the dose‐response relationship for NA.
Fatigue of mechanical responses of the taenia to perivascular nerve stimulation was accelerated when nerves were stimulated in the presence of 5‐HT or α‐methyl‐p‐tyrosine (α‐MPT). These two agents were additive in this action.
Reserpine, 6‐hydroxydopamine and α‐MPT all reduced the NA content of the taenia. However, only after 6‐hydroxydopamine could adrenergic activity be related to NA content.
Segments of taenia were incubated with either tritiated NA or 5‐HT. An increased rate of release of radioactivity followed perivascular nerve stimulation after incubation with either substance. This release did not occur when tissue was taken from animals given reserpine or 6‐hydroxydopamine.
It is concluded that 5‐HT activates neural elements exclusively while NA has a direct effect on smooth muscle. 5‐HT can apparently be taken up by adrenergic axons, and appears to enter the releasable neurotransmitter pool. Since none of the actions characteristic of 5‐HT are seen when it is released by adrenergic axons as a false neurotransmitter, the released amine probably fails to reach neuronal receptors for 5‐HT.
Effect of glucocorticoids on histamine metabolism in mice
Authors: REILLY MARGARET A. , SCHAYER R. W. 
Published: July 2012

Summary
Histamine formation and catabolism were studied in vivo in standardized experiments; for the former, animals pretreated with inhibitors of histamine catabolism were killed 10 min after intravenous injection of 14C‐L‐histidine; for the latter, no inhibitors were used and animals were killed 2·5 min after intravenous injection of 14C‐histamine. In vitro assays of histidine decarboxylase activity were also made.
Pretreatment of adrenalectomized mice with cortisol for one day caused a major alteration in histamine formation; stomach and intestine were abnormally high in the 14C‐histamine: total 14C ratio, while most other tested tissues were lower. Brain and thymus were unaffected. Cortisol treatment caused a marked increase in urinary excretion of both 14C‐histamine and total 14C.
Following injection of a rapidly absorbed corticoid, significant effects on urine and stomach were demonstrable at 30 min and 4 h, respectively.
In cortisol‐treated adrenalectomized mice histidine decarboxylase activity, relative to controls, was decreased in lung but virtually unaffected in kidney, heart, muscle and liver. In stomach, activity was increased but the statistical significance was low.
In mice injected with 14C‐histamine, cortisol pretreatment caused a small drop in tissue levels of 14C‐histamine, 14C‐methylhistamine and total 14C, but increased levels in urine. In all cases, however, the ratio of the two amines to total 14C was not significantly different from controls.
From the foregoing experiments it was concluded that the results in (2) could be largely attributed to entry into urine of 14C‐histamine and total 14C, thus reducing the availability of these substances in blood for extraction by tissues. In stomach, the cortisol‐induced increase in histamine formation may involve some process other than increased histidine decarboxylase activity.
The activation of histidine decarboxylase in liver and lung of intact mice by Freund's adjuvant, or by endotoxin, was reduced by corticoid treatment.
In a single short experiment on the effect of cortisol on histamine formation in adrenalectomized rats, results from stomach, lung and heart, the only tissues assayed, were similar to those from the mouse experiment.
A comparison of the pharmacological and biochemical properties of substrate‐selective monoamine oxidase inhibitors
Authors: CHRISTMAS A. J. , COULSON C. J. , MAXWELL D. R. , RIDDELL D. 
Published: July 2012

Summary
M&B 9302, E‐250, NSD 2023, and Lilly 51641, substrate‐selective inhibitors of monoamine oxidase (MAO), and two non‐selective inhibitors of MAO (tranylcypromine and phenelzine) have been compared in the rat for activity in (i) inhibiting rat brain monoamine oxidase in vitro and in vivo using tyramine, 5‐hydroxytryptamine (5‐HT) and benzylamine as substrates; (ii) increasing brain levels of noradrenaline (NA) and 5‐HT and (iii) antagonizing tetrabenazine‐induced sedation.
Concentrations of M&B 9302 and Lilly 51641 required to produce 50% inhibition of 5‐HT oxidation by brain mitochondrial MAO were 1·4 × 10−8M and 2·5 × 10−7M respectively. Higher concentrations were required to inhibit tyramine oxidation whilst benzylamine oxidation was inhibited only at concentrations above 10−5M.
E‐250 showed the reverse substrate‐selectivity in inhibiting the oxidation of benzylamine at concentrations below that required to inhibit the oxidation of 5‐HT. NSD 2023 showed little substrate selectivity in vitro.
Qualitatively similar results were obtained in vivo, except that NSD 2023 showed more marked substrate‐selectivity.
All the inhibitors except E‐250 produced a dose‐related rise in brain 5‐HT levels. Only phenelzine and Lilly 51641 showed a linear relationship between NA levels and dose.
All the drugs antagonized, in dose‐related fashion, the effects of tetrabenazine in reducing locomotor activity. E‐250 and NSD 2023 failed to restore locomotor activity to control levels whilst in high doses the other inhibitors, when given before tetrabenazine, produced a considerable increase in locomotor activity.
Antagonism of tetrabenazine sedation appears to be correlated with (a) inhibition of the enzyme species that oxidize 5‐HT and NA but not with inhibition of the enzyme species that oxidize benzylamine; (b) the rise in brain 5‐HT levels rather than NA levels.
A structure‐activity study of sympathomimetic amines on the beta‐adrenoceptors of guinea‐pig trachea
Authors: CHAHL LORIS A. 
Published: July 2012

Summary
The relative activities of a large number of sympathomimetic amines were estimated on the β‐adrenoceptors of the guinea‐pig tracheal chain preparation. Concentrations which produced half‐maximal responses were measured for each drug and the maximum responses were also noted and expressed as a percentage of that produced by isoprenaline.
The relative activities of the amines generally decrease with loss of hydroxyl groups from the structure, and amines with less than two hydroxyl groups produce little or no observable response.
The affinity constants of the partial agonists and antagonists were measured. The hydroxyl group on the β carbon atom of the side chain, N‐alkyl groups and an α carbon methyl group increase affinity, whereas the p‐phenolic group decreases affinity. The m‐phenolic group does not seem to affect affinity.
By comparing the effects of groups on affinity with their effects on activity, it was deduced that N‐alkyl groups, m‐ and p‐phenolic groups and probably also the β carbon hydroxyl group increase efficacy. Alpha carbon methylation appears to reduce efficacy.