bluuebunny/crossref_metadata_2025_split huggingface dataset:
INHIBITION OF LYMPHOCYTE PROLIFERATION BY HISTAMINE AND RELATED COMPOUNDS NOT MEDIATED VIA H1‐ OR H2‐ RECEPTORS
Authors: GORDON D. , LEWIS G.P. , NOURI A.M.E. 
Published: July 2012

The effects of histamine and chemical analogues were examined on mitogen‐stimulated human lymphocyte proliferation
Compounds with selective agonist activity at either H1‐ or H2‐receptors were found to inhibit proliferative responses, although N‐3‐methyl‐histamine which does not act on either receptor was as inhibitory as histamine itself
The H2‐receptor agonist, dimaprit, had a profound inhibitory effect on proliferation, however nordimaprit, which has little or no H2‐agonist activity, was more active on lymphocytes. Impromidine, although a potent H2‐agonist, failed to produce such inhibition
The effects of dimaprit and nordimaprit were not reversed by H2‐receptor antagonists, cimetidine or metiamide
These results do not support the view that the antiproliferative effects of histamine and related compounds are mediated via conventional H1‐ or H2‐receptors
SKF 93390 was found to be the most active of the dimaprit analogues tested, which could represent a novel series of potential immunosuppressive agents.
THE ROLE OF CALCIUM IN THE EFFECTS OF NORADRENALINE AND PHENOXYBENZAMINE ON ADRENERGIC TRANSMITTER RELEASE FROM ATRIA: NO SUPPORT FOR NEGATIVE FEEDBACK OF RELEASE
Authors: KALSNER STANLEY 
Published: July 2012

The relation of calcium ion influx into nerve terminals to presynaptic adrenoceptor function and the possible masking, by desensitization due to intraneuronal calcium accumulation, of the effects of adrenoceptor agonists and antagonists on presynaptic α‐adrenoceptors was investigated in guinea‐pig atria previously incubated with [3H]‐noradrenahne.
Atria were stimulated with 100 pulses at various frequencies (1 to 15 Hz) in standard (2.3 mm), low (0.26 mm) and high (6.9 mm) calcium‐Krebs solution in the absence and then the presence first of noradrenaline and subsequently phenoxybenzamine.
The per pulse overflow of tritium was directly related to the calcium concentration of the Krebs solution, being much reduced and substantially increased in 0.26 and 6.9 mm calcium‐Krebs solutions respectively.
Noradrenaline inhibited the overflow of tritium in low calcium‐Krebs solution, to a relatively constant extent, independently of frequency. In addition, the agonist had a greater maximal inhibitory effect in standard than in reduced calcium‐Krebs. The catecholamine was as effective an inhibitor of overflow at the lowest and highest frequencies in high as it was in standard calcium‐Krebs solution. Phenoxybenzamine invariably increased the tritium overflow but was generally less effective both in low and in high calcium‐Krebs solution. The patterns of inhibition and enhancement of stimulation‐induced tritium overflow by these two agents do not indicate an intimate relationship between calcium influx and adrenoceptor activation; nor does desensitization appear to be an adequate explanation of the relationship between frequency of stimulation and the intensity of agonist and antagonist effect in the three different calcium concentrations.
It is concluded that the perineuronal levels of adrenergic transmitter do not establish the magnitudes of effect of exogenous adrenoceptor agonists and antagonists on tritium overflow and that a negative feedback regulation of release by transmitter is exceedingly unlikely under ordinary conditions of neurotransmission.
IDENTIFICATION OF A PURINE (P2) RECEPTOR LINKED TO ION TRANSPORT IN A CULTURED RENAL (MDCK) EPITHELIUM
Authors: SIMMONS N.L. 
Published: July 2012

Exogenous adenosine triphosphate (ATP) stimulates the short circuit current (SCC) in a cultured renal‐derived epithelium (MDCK). Half‐maximal stimulation is achieved at 1.91 × 10−5m ATP.
It is suggested that ATP interacts with a P2 purine receptor upon the basis of (a) agonist potency (ATP > adenosine diphosphate >> adenosine monophosphate, adenosine; ATP> uridine triphosphate > inosine triphosphate >> cytosine triphosphate, guanosine triphosphate); (b) the inhibition of the ATP response by quinidine (1×10−3m) but not by theophylline (1×10−3m).
Indomethacin (1 × 10−5m) inhibits the response of the cultured epithelium to ATP.
Prostaglandin E1 (PGE1) stimulates SCC but potentiates the effect of ATP on SCC. The divalent cationic ionophore A23187 (1 × 10−6m) transiently stimulates SCC itself and abolishes ATP‐induced stimulation of the SCC.
ON THE CALCIUM RECEPTOR THAT MEDIATES DEPOLARIZATION‐SECRETION COUPLING AT CHOLINERGIC MOTOR NERVE TERMINALS
Authors: SILINSKY E.M. 
Published: July 2012

The behaviour of the divalent cations Ca and Sr as agonists for receptors that mediate the synchronous evoked secretion of acetylcholine (ACh) was studied in the hope of determining whether the relationship between Ca binding and ACh secretion is determined only by the law of mass action or by the mathematical framework of receptor theory. Experiments were designed to evaluate the assumption that maximum effect requires occupation of all receptors by testing for the presence of spare Ca receptors on presynaptic terminals. Frog cutaneous nerve‐muscle preparations were employed in conjunction with conventional electrophysiological methods.
Curves of log [Ca] or log [Sr] against the mean number of ACh quanta released (m) were constructed to saturation. The log [Sr]‐m relationship was shifted to the right and had a smaller maximum than the log [Ca]‐m curve. This suggests that Ca has a higher efficacy than Sr and raises the possibility that spare binding sites are present for Ca.
As a qualitative test for spare Ca receptors, La3+(≤0.5 μm) or 2‐chloroadenosine (25 μm) was employed as an irreversible antagonist of the effects of extracellular Ca on evoked ACh release. Despite the irreversible blockade of a proportion of receptors, increases in the [Ca] overcame this antagonism and produced a parallel shift in the log [Ca]‐m relation to the right. This suggests an apparent receptor reserve for Ca. Antagonism of Sr‐mediated ACh release by either La3+ or 2‐chloroadenosine could not be overcome by increasing the [Sr].
As a quantitative test for spare Ca binding sites, the equilibrium affinity constant for Sr(KSr) as a competitive inhibitor of Ca was determined and compared with values for KSr calculated by two other methods which invoke the spare receptor assumption. All three methods produced comparable results. (KSr = 0.24‐0.27 mm−1).
The equilibrium affinity constant for Ca (KCa) was calculated by comparing reciprocal plots of the concentrations of Ca that produce equal levels of ACh release in the presence and absence of La3+(0.5 μm‐3 μm). KCa was estimated to be between 0.02 and 0.06 mM−1.
Efficacy (e), which is thought to reflect the ability of Ca or Sr once bound to receptors to support ACh release, was determined by the modified occupation theory of Stephenson (1956). The eCa was estimated to be 9–20 and eSr was 0.2‐0.5.
The experimentally determined values for ATCa, KSt, eCa, eSr along with the assumptions that spare Ca binding sites exist and that the non‐linearities in the log [Ca] or log [Sr]‐m curves are introduced beyond the sites of binding and efficacy were used to generate theoretical log [Me]‐m curves. The theoretical relationships were similar to the experimental results.
The results suggest that spare Ca receptors are present at motor nerve endings and that receptor theory provides an accurate quantitative description of the lumped events between Ca binding and ACh secretion. The possible physical correlates of affinity and efficacy are discussed.
THEOPHYLLINE INHIBITION OF RENAL AND CEREBRAL NUCLEOSIDE FORMATION
Authors: JENSEN MOGENS H. 
Published: July 2012

Theophylline inhibits the enzymatic formation of purine nucleosides, among these adenosine (dephosphorylated adenosine 5′‐monophosphate), in kidney and brain of the rat.
Some pharmacological effects of theophylline on regional blood flow and electrophysiological activity of the nervous system may be caused by inhibition of the endogenous formation of adenosine.
THE EFFECTS OF ATROPINE AND OXOTREMORINE ON ACETYLCHOLINE RELEASE IN RAT PHRENIC NERVE‐DIAPHRAGM PREPARATIONS
Authors: ABBS E.T. , JOSEPH D.N. 
Published: July 2012

Atropine (10−5m) enhanced the release of [3H]‐acetylcholine from rat isolated hemidiaphragms, previously incubated with [3H‐methyl]‐choline, stimulated via their phrenic nerves.
Oxotremorine (10−5m) did not affect the stimulated release of [3H]‐acetylcholine but antagonized the facilitatory effects of atropine (10−5m).
It is suggested that there are presynaptic inhibitory muscarinic receptors that modulate the release of acetylcholine in the phrenic nerves of the rat.
INHIBITION OF ARACHIDONIC ACID RELEASE AS THE MECHANISM BY WHICH GLUCOCORTICOIDS INHIBIT ENDOTOXIN‐INDUCED DIARRHOEA
Authors: DOHERTY NIALL S. 
Published: July 2012

Dexamethasone blocked endotoxin‐induced diarrhoea in mice, but not that induced by arachidonic acid or prostaglandin E2.
Indomethacin blocked endotoxin and arachidonic acid‐induced diarrhoea, but not that induced by prostaglandin E2.
Codeine blocked all three forms of diarrhoea.
The above data, when considered in relation to literature reports that endotoxin induces prostaglandin synthesis, suggest that dexamethasone blocks diarrhoea by preventing the release of arachidonic acid, the substrate for prostaglandin biosynthesis.
The activities of indomethacin and dexamethasone in castor oil diarrhoea support the above conclusion and their inactivity in 5‐hydroxytryptophan‐induced diarrhoea confirms the absence of ‘codeine‐like’ direct effects on the gut.
Other glucocorticoids (hydrocortisone, prednisolone) were also able to block endotoxin diarrhoea, but oestradiol, testosterone and progesterone did not.
The inhibitory action of dexamethasone on endotoxin diarrhoea could not be blocked by the protein synthesis inhibitor, cycloheximide, nor by the glucocorticoid receptor antagonist, progesterone. Thus, involvement of glucocorticoid receptor‐mediated gene activation could not be demonstrated.
EVIDENCE FOR AN INHIBITORY PRESYNAPTIC COMPONENT OF NEUROLEPTIC DRUG ACTION
Authors: de BELLEROCHE J.S. , BRADFORD H.F. 
Published: July 2012

The action of five neuroleptic drugs (haloperidol, cis‐flupenthixol, chlorpromazine, fluphenazine and thioridazine) was studied on the synthesis and release of dopamine from rat striatal synaptosomes.
In vitro application of the drugs induced an inhibition of synthesis of [14C]‐dopamine from l‐[U‐14C]‐tyrosine and a decrease in the tissue content of [14C]‐dopamine, with IC50 values for the latter effect ranging from 3.6 × 10−7 to 5.9 × 10− 5 m. The rank order of their potency was similar to the order of their clinical effectiveness: haloperidol>fluphenazine>cis‐flupenthixol>chlorpromazine>thioridazine. Trans flupenthixol was without effect up to a concentration of 10−4 m.
The tissue level and release of GABA were not affected by concentrations of the neuroleptics up to 10−4 m.
When the neuroleptics were administered in vivo, changes were also detected in the synthesis and release of [14C]‐dopamine from subsequently prepared synaptosomes. A marked inhibition of the K+‐induced increase in [14C]‐dopamine synthesis was seen following a dose of 2 mg/kg cis‐flupenthixol and haloperidol. At this concentration, haloperidol also increased the control release of [14C]‐dopamine and reduced the K+‐induced increase in release of [14C]‐dopamine.
Cis‐flupenthixol at a dose of 20 mg/kg reduced the K+‐induced release of [14C]‐dopamine by 48% and to a lesser extent, that of γ‐aminobutyric acid (GABA, 25%).
An inhibitory mode of action is proposed for neuroleptics mediated through a presynaptic mechanism.
ENKEPHALIN RECEPTORS IN THE EMETIC CHEMORECEPTOR TRIGGER ZONE OF THE DOG
Authors: BHARGAVA K.P. , DIXIT K.S. , GUPTA Y.K. 
Published: July 2012

The emetic action of Met‐enkephalin, morphine and naloxone was studied following their administration into the cerebral ventricles of dogs through chronically implanted cannulae and the effect on the responses of ablating the chemoreceptor trigger zone (CTZ) was investigated. The opiate antagonist, naloxone, was used to determine the role of enkephalin receptors in emetic responses.
Administration of Met‐enkephalin (1.0 μg/kg) into the IVth ventricle regularly evoked emesis with an average latency of 35 s. A dose of morphine (2.5 μg/kg) which was five times larger was required for a consistent emetic response when introduced into the lateral cerebral ventricle (i.c.v.) as compared to the dose required by the IVth ventricular route. The latency of emetic responses by the latter route of injection of morphine was shorter. This is in accord with an action of morphine on the emetic CTZ.
After bilateral ablation of the CTZ, intraventricular injections of Met‐enkephalin and morphine failed to produce emesis even when given in doses that were 5 to 10 times the dose which regularly elicited emesis in animals with intact CTZ. The emesis produced in dogs by intraventricular Met‐enkephalin and morphine is thus fully accounted for by an action on the CTZ.
Naloxone (i.c.v.) in doses up to 10.0 μg/kg did not cause emesis. However, higher doses of naloxone elicited dose‐dependent emesis in dogs. The 100% emetic dose of naloxone was found to be 160 μg/kg and the latency of emesis was 180 s. Unlike Met‐enkephalin and morphine, naloxone continued to elicit emesis in CTZ‐ablated animals.
Pretreatment with intraventricular naloxone (1 to 8 μg/kg) blocked the emetic responses induced by intraventricular Met‐enkephalin and morphine but not that to apomorphine. The selective protective action of the opiate antagonist against Met‐enkephalin and morphine supports the presence of enkephalin receptors in the emetic CTZ.
THE EFFECTS OF CHRONIC SECTION OF DORSAL ROOTS ON THE RESPONSIVENESS OF MOTONEURONES TO 5‐HYDROXYTRYPTAMINE AND A SUBSTANCE P ANALOGUE
Authors: ROBERTS M.H.T. , WRIGHT D. M. 
Published: July 2012

Experiments were performed on rats 14–21 days after unilateral dorsal root section in order to determine if the effects on motoneurone excitability of a substance P analogue, 5‐hydroxy‐tryptamine (5‐HT) and noradrenaline were altered by section of primary afferents.
The effects of iontophoretic applications of these agents on motoneurone excitability were quantified by measuring the change in amplitude of the short latency field potentials evoked antidromically, by ventral root stimulation.
Iontophoretic application of the substance P analogue (eledoisin‐related peptide, ERP) always produced an increase in the amplitude of the field potential. These increases in amplitude were 25.9% larger on the sides of the cords with sectioned dorsal roots. This was not a statistically significant difference (P<0.05).
Section of dorsal roots did not alter responses to noradrenaline.
Responses to 5‐HT were significantly larger following section of dorsal roots. There is very little evidence for the release of 5‐HT by primary afferents and denervation supersensitivity is an improbable explanation. It is possible that descending 5‐HT systems directly excite motoneurones and indirectly inhibit primary afferent transmission. Dorsal root section would alter the balance between these actions of 5‐HT in favour of an excitatory effect.
MECHANISM OF ANTI‐INFLAMMATORY ACTION OF GLUCOCORTICOIDS: RE‐EVALUATION OF VASCULAR CONSTRICTION HYPOTHESIS
Authors: SUGIO KAZUO , TSURUFUJI SUSUMU 
Published: July 2012

The question whether constriction of local vessels is essential for the anti‐inflammatory action of glucocorticoids in carrageenin‐induced granulomatous inflammation was studied.
The vasodilator prostaglandin E1 injected into the granuloma pouch fluid increased the exudation of plasma protein into the granuloma tissue.
Noradrenaline significantly reduced plasma exudation, possibly through α‐adrenoceptor stimulation.
Cortisol and dexamethasone in doses sufficient to inhibit vascular permeability were without effect on the blood content in the granuloma tissue.
The results suggest that constriction of local vessels does not play an essential role in the anti‐exudative effect of glucocorticoids in chronic proliferative inflammation.
PHARMACOLOGICAL DATA ON DERMORPHINS, A NEW CLASS OF POTENT OPIOID PEPTIDES FROM AMPHIBIAN SKIN
Authors: BROCCARDO M. , ERSPAMER V. , FALCONIERI G. , IMPROTA G. , LINARI G. , MELCHIORRI P. , MONTECUCCHI PC. 
Published: July 2012

Dermorphin and Hyp6‐dermorphin are the first representatives of a new class of potent opioid peptides occurring in amphibian skin. They present the unique feature of having a D‐Ala residue incorporated in the peptide molecule.
Dermorphin displayed a potent depressive action on electrically stimulated contractions of the guinea‐pig ileum and mouse vas deferens preparations. Dermorphin was respectively 57,294, 18 and 39 times more potent than Met‐enkephalin, Leu‐enkephalin, β‐endorphin, and morphine on the guinea‐pig ileum opiate receptors. On the vas deferens receptors, dermorphin was about as potent as the enkephalins and 40 times more potent than morphine. Naloxone was a powerful antagonist to dermorphin in both preparations.
Dermorphin produced potent and long‐lasting analgesia in mice by intravenous injection, and in rats by intracerebroventricular injection, the ED50 being here of the order of 13–23 pmol/rat. Morphine was 752 and 2170 times less potent, depending on the analgesia test used. At high intracerebroventricular doses analgesia was accompanied by catalepsy.
Intracerebroventricular infusion of dermorphin induced development of tolerance and precipitation of withdrawal symptoms upon administration of naloxone. Both tolerance and physical dependence were consistently less marked with dermorphin than with morphine.
The minimum sequence requirement for full dermorphin activity was represented by the N‐terminal tetrapeptide. The presence of the D‐Ala2 residue was of crucial importance.
EFFECTS OF DIVALENT AND LANTHANIDE IONS ON MOTILITY INITIATION IN RAT CAUDAL EPIDIDYMAL SPERMATOZOA
Authors: LEE W.M. , TSANG A.Y.F. , WONG P.Y.D. 
Published: July 2012

Sperm motility initiation of rat caudal epididymal spermatozoa in vitro has been studied.
Spermatozoa flushed out from the cauda epididymis with a sodium‐free medium exhibited a transient motility which decreased progessively. At 40 min, the forward motility was completely suppressed. However, if they were resuspended in a sodium containing medium their motility was completely restored to normal within 15 min.
This initiation of sperm motility required the presence of extracellular calcium. Maximal stimulation was obtained at a calcium concentration of 10 −3M. Above this concentration, further increase in calcium produced a fall in motility and at 10 −2M, motility initiation was completely suppressed.
The initiation of sperm motility has been shown to depend closely on sodium. Sperm motility initiation alters in a curvilinear fashion with extracellular sodium concentration showing saturation kinetics. High calcium (above 10−3m) was found to depress motility initiation induced by sodium, without affecting the apparent affinity constant for sodium.
The effect of Ca2+ on sperm motility initiation could be mimicked by Sr2+ but not by Mg2+, La3+ or Eu3+.
In the presence of extracellular calcium (1.27 or 2.54 mM), La3+ and Eu3+ exerted a dose‐dependent inhibition of sperm motility initiation. The IC50 values for both ions were about 5 × l0−5M.
The possible mechanism of inhibition by lanthanide ions is discussed.
ON THE MECHANISM BY WHICH VERATRIDINE CAUSES A CALCIUM‐INDEPENDENT RELEASE OF γ‐AMINOBUTYRIC ACID FROM BRAIN SLICES
Authors: CUNNINGHAM JO , NEAL M.J. 
Published: July 2012

The mechanisms by which veratridine increases the release of γ‐aminobutyric acid (GABA) from brain slices have been studied.
Exposure of superfused cerebro‐cortical, nigral or cerebellar slices to veratridine (5 μm) or KC1 (50 mM) caused large increases in the efflux of [3H]‐GABA.
Reduction of the external Ca concentration [Ca]0 to zero had strikingly different effects on the veratridine and K‐evoked release of [3H]‐GABA. The K‐evoked release from all three areas was greatly reduced in Ca‐free medium, but the veratridine‐evoked release from cerebeller slices was not affected, and the release of [3H]‐GABA from cortical and nigral slices was increased three fold. The potentiation of the veratridine evoked release of GABA which occurred in Ca‐free medium was not due to the reduction in divalent ions, because it still occurred in medium in which the Ca was replaced by an equivalent amount of Mg.
The veratridine‐evoked release of [14C]‐glycine from slices of spinal cord was also significantly increased in Ca‐free medium. In contrast, the release of cortical [3H]‐noradrenaline and [14C]‐acetylcholine caused by the alkaloid was greatly diminished in Ca‐free medium.
The veratridine but not the K‐evoked release of [3H]‐GABA was abolished when the external Na concentration [Na]0 was reduced to zero and by tetrodotoxin (TTX) (0.2 μm). Cl‐free medium did not affect the veratridine‐evoked release of [3H]‐GABA or its potentiation by Ca‐free medium.
Exposure of the tissue to depolarizing concentrations of external K ([K]0 = 120 mM) did not abolish the veratridine evoked release of [3H]‐GABA or its potentiation by Ca‐free medium.
Pre‐incubation of cortical slices with L‐2,4, diaminobutyric acid (DABA), or substitution of Na in the superfusion medium with Li, did not affect the veratridine‐evoked release of [3H]‐GABA, indicating that the alkaloid does not stimulate GABA efflux by a carrier‐mediated transport process.
Exposure of the tissue to ruthenium red (10 μm) increased the veratridine evoked release of [3H]‐GABA in both normal and in Ca‐free medium but almost abolished the K‐evoked release.
It is suggested that veratridine causes GABA release by increasing the permeability of the nerve terminals to Na. In normal medium, the resulting influx of Ca2+ ions through voltage‐dependent Ca2+ channels may be involved in triggering the release of GABA. However, a major part of the GABA efflux appears to be triggered by the release of Ca2+ ions from intraterminal mitochondria, which results from the increase in[Na]i. Since Ca2+ ions antagonize the action of veratridine, the potentiation of the drug‐evoked release of GABA that occurs in Ca‐free medium, might be due to the absence of the antagonistic Ca2+ ions. The resulting greater increase in Na entry and [Ca]i caused by Ca release from intracellular stores, must presumably more than balance the contribution normally made by any influx of extracellular Ca2+.
DIVALENT CATIONS INCREASE [3H]‐PROSTACYCLIN BINDING TO MEMBRANES OF NEURONAL SOMATIC HYBRID CELLS
Authors: BLAIR IAN A. , CRESP TERRY M. , MacDERMOT JOHN 
Published: July 2012

[3H]‐prostacyclin binding to membranes of a highly differentiated neuronal somatic hybrid is increased equally in the presence of Ca2+, Ba2+, Mg2+ or Sr2+ ions.
Analysis of the binding of [3H]‐prostacyclin in the presence of low (1 mm) or high (50mm) Mg2+ ion concentrations has revealed a cation‐dependent increase in ligand receptor affinity (Kd− values = 57.4 nM and 21.9 nM).
The increase in [3H]‐prostacyclin binding due to divalent cations is not accompanied by an alteration in the maximum binding capacity of the membranes.