bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CYTOCHEMICAL BIOASSAY METHOD FOR THE DETERMINATION OF LUTEINIZING HORMONE IN BIOLOGICAL FLUIDS AND TISSUES
Authors: BUCKINGHAM JULIA C. , HODGES J.R. 
Published: July 2012

The ability of luteinizing hormone (LH) to alter the reducing activity of corpora lutea in rat ovarian sections has been exploited to develop a new cytochemical bioassay for the hormone.
Sections of ovaries, removed from mature rats during the second day of dioestrus, were incubated with either standard LH or samples diluted for assay, stained immediately for reducing potential and the intensity of the stain measured by scanning and integrating microdensitometry.
An inverse linear relationship existed between the density of the stain and the logarithm of the concentration of standard LH (68/40) and the dose‐response lines of serial dilutions of rat or human plasma were parallel with those of the standard.
The method was found to be accurate, specific, sensitive, precise and suitable for the determination of LH in the rat and in man.
CHARACTERISTICS OF (±)‐[14C]‐OXPRENOLOL AND (±)‐[14C]‐PROPRANOLOL INCORPORATION BY RAT LUNG SLICES
Authors: HEMSWORTH BRIAN A. , STREET JAMES A. 
Published: July 2012

The uptake of (±)‐[14C]‐oxprenolol and (±)‐[14C]‐propranolol has been studied in rat lung slices. The loss of these two radiolabelled β‐adrenoceptor antagonists from pre‐loaded lung slices has also been studied.
Over the concentration range studied (3.3 × 10−7m to 1.7 × 10−3m) a biphasic uptake of both compounds was observed. At concentrations below 1.5 × 10−4m approximately, there was some evidence of saturability, but at higher concentrations uptake appeared to be a linear function of drug concentration.
At concentrations of 6.6 × 10−7m and 1.7 × 10−6m respectively, the uptake of oxprenolol and propranolol was significantly reduced by low temperature, anaerobic conditions, incubation in Na+‐free medium, and by the metabolic inhibitors potassium cyanide and 2, 4‐dinitrophenol. Ouabain had little or no effect.
At the same concentration, oxprenolol uptake was also inhibited in a concentration‐dependent manner by propranolol, amphetamine, chlorpromazine and imipramine. Noradrenaline was without effect.
The loss of oxprenolol and propranolol from lung slices preloaded with the two compounds was fairly slow, with 60 to 70% of the drug originally taken up still remaining in the tissue after 30 min in fresh medium.
Possible mechanisms underlying the pulmonary accumulation of oxprenolol and propranolol are discussed.
A TEST OF THE NULL EQUATION FOR FUNCTIONAL ANTAGONISM
Authors: EMMERSON JANE , MACKAY DENNIS 
Published: July 2012

The quantitative model for functional antagonism and synergism has been tested by studying its ability to fit data obtained from the functional antagonism of (−)‐isoprenaline by muscarinic agonists on guinea‐pig isolated atria.
The general form of the null equation has been shown to fit the experimental curves satisfactorily.
Functional interaction between (–)‐soprenaline and muscarinic agonists on atria has been shown to be type I although there does seem to be a discrepancy between values of the functional affinity constants. KA1F and KA2F estimated in two different ways.
The affinity constants, KA. of the muscarinic agonists for their receptors have been estimated by use of the selective irreversible antagonist propylbenzilylcholine mustard. The discrepancy between KAF (i.e. both KA1F and KA2F) and KA is small for pentyltrimethylammonium which is an agonist of low intrinsic efficacy. By contrast the discrepancy between KAF and KA is much greater for methyl‐furmethide and oxotremorine both of which have much higher intrinsic efficacies. These results are as predicted by the model.
It is suggested that the discrepancy between KA1F and KA2F may be due to the limited ability of the equation
to describe quantitatively the relation between sequential stimuli. However, it is concluded that this complication need not interfere with the use of the model to study mechanisms and possible sites of functional interaction.
THE SPONTANEOUS AND EVOKED RELEASE OF SPERMINE FROM RAT BRAIN in vitro
Authors: HARMAN R.J. , SHAW G.G. 
Published: July 2012

The efflux of previously accumulated [3H]‐spermine from brain slices was measured using a continuous perfusion system. The spontaneous efflux was biphasic, consisting of an initial rapid efflux followed by a much slower release.
The slices were depolarized by the addition to the medium of high potassium concentrations, ouabain or veratrine.
At concentrations greater than 30 mM, potassium evoked a striking increase in the release of [3H]‐spermine. Following uptake in the presence of 5.7 × 10−9M[3H]‐spermine, K+‐evoked release was dependent on the presence of calcium ions. Release of spermine after uptake at 5.6 × 10−8m or 5.0 × 10−7m was not calcium‐dependent.
The calcium‐dependent, K+‐stimulated release of spermine was inhibited in the presence of diphenylhydantoin (5 × 10−3m) or ruthenium red (10−3 m).
Following uptake of 5.7 × 10−9m [3H]‐spermine in a sodium‐free medium, the calcium‐dependent, K+‐stimulated release was significantly inhibited.
Ouabain (10−4m) caused a large but calcium‐independent increase in the efflux of [3H]‐spermine.
Veratrine‐induced release was less substantial but was increased in a calcium‐free medium. Release evoked by veratrine was abolished in the absence of sodium.
These results are discussed with respect to a possible ‘neurotransmitter’ or ‘neuromodulator’ role for spermine.
A COMPARISON OF THE CARDIOVASCULAR AND SEDATIVE ACTIONS OF THE α‐ADRENOCEPTOR AGONISTS, FLA‐136 AND CLONIDINE, IN THE RAT
Authors: HAMILTON T.C. , LONGMAN SUSAN D. 
Published: July 2012

The cardiovascular and sedative effects of FLA‐136 have been compared with those of clonidine after intracerebroventricular (i.c.v.) administration in the rat. The effects of both drugs on pre‐ and postsynaptic α‐adrenoceptors in the periphery have been investigated after intravenous (i.v.) administration in the pithed rat.
In the anaesthetized rat, i.c.v. FLA‐136 and clonidine produced dose‐related hypotension, FLA‐136 having three to 30 times less activity than clonidine; both drugs caused concomitant bradycardia. In the conscious rat i.c.v. FLA‐136 had less sedative potential than clonidine, in terms of overt sedation assessed visually.
Yohimbine reduced the hypotension and bradycardia produced by i.c.v. FLA‐136 and clonidine; prazosin and mianserin also antagonized the cardiovascular responses to clonidine, but not those to FLA‐136.
Chemical sympathectomy by 6‐hydroxydopamine (6‐OHDA) markedly reduced the cardiovascular effects of FLA‐136 but only slightly reduced those of clonidine.
Naloxone antagonized the cardiovascular responses to clonidine, but not FLA‐136, suggesting a direct or indirect involvement of central opiate receptors in the responses induced by clonidine.
Metiamide attenuated the cardiovascular responses to FLA‐136 and clonidine, implying a direct or indirect involvement of central histamine (H2)‐receptors in such responses.
FLA‐136, unlike clonidine, did not stimulate peripheral pre‐ or postsynaptic α‐adrenoceptors in the pithed rat.
FLA‐136 is a novel centrally‐acting hypotensive compound which, unlike clonidine, selectively stimulates central α‐autoreceptors (yohimbine‐sensitive) in the rat; these autoreceptors may be different from peripheral pre‐ and postsynaptic α‐adrenoceptors. The results suggest that clonidine lowers blood pressure by stimulation of two types of central postsynaptic α‐adrenoceptors in the rat, ‐one type being sensitive to yohimbine and the other to prazosin.
DIFFERENTIAL ACTIONS ON RABBIT NODAL, ATRIAL, PURKINJE CELL AND VENTRICULAR POTENTIALS OF MELPERONE, A BRADYCARDIC AGENT DELAYING REPOLARIZATION: EFFECTS OF HYPOXIA
Authors: MILLAR J.S. , WILLIAMS E.M. VAUGHAN 
Published: July 2012

Melperone, a butyrophenone tranquillizer, caused bradycardia in vivo and in vitro.
Although Melperone had α‐adrenoceptor antagonist activity in the pithed rat, it was not a β‐adrenoceptor antagonist, nor was it a cholinoceptor agonist.
The bradycardic action could be attributed almost entirely to a prolongation by Melperone of action potential duration (APD) in sinus node cells, with little effect on the slow diastolic depolarization.
APD was prolonged by Melperone in atrial and ventricular muscle, and most of all in the bundle of His, but only moderately in the terminal Purkinje cells.
In all cardiac tissues depolarized by fast inward current, Melperone caused a dose‐related reduction in the maximum rate of depolarization and conduction velocity. On desheathed frog nerve Melperone had a local anaesthetic potency equal to that of procaine.
There was no negative inotropic effect in cardiac muscle, nor interference with A‐V nodal conduction, from which it was inferred that Melperone did not restrict slow inward current.
Melperone did not reduce hypoxic shortening of APD relative to the initial value at the start of hypoxia, but because APD was already lengthened by Melperone in normoxic conditions, APD90 during hypoxia remained close to normal values. There was no protection against hypoxic depression of contractions.
It was concluded that Melperone had class 1 and class 3 antiarrythmic actions and merited trial as an antiarrhythmic drug.
ANALYSIS OF HISTAMINE RECEPTORS IN THE CENTRAL THERMOREGULATORY MECHANISM OF Mastomys natalensis
Authors: DHAWAN B.N. , SHUKLA R. , SRIMAL R.C. 
Published: July 2012

The effect of intracerebroventricular (i.c.v.) injection of histamine on the rectal temperature of Mastomys natalensis at ambient temperatures of 10, 24 and 33°C has been studied.
Low doses (0.1–1.0 μg) of histamine produced hypothermia while larger doses (5–20 μg) produced dose‐dependent hyperthermia. The hypothermic effect was significantly antagonized by mepyramine while the hyperthermia was blocked by cimetidine.
Histamine H1‐receptor agonists, 2‐methyl‐histamine and 2‐pyridyl‐ethylamine, also produced hypothermia which could be blocked by mepyramine.
Histamine H2‐receptor agonists, impromidine and dimaprit, produced hyperthermia which was antagonized by cimetidine.
Pretreatment of the animals with a β‐adrenoceptor antagonist, MJ1999, did not affect the response to histamine.
The hyperthermic effect of histamine (10 μg) was most marked at 10°C and was attenuated at 33°C.
It is concluded that both H1‐ and H2‐histamine receptors are present in the brain of Mastomys. The H1‐receptors mediate hypothermia and H2‐receptors hyperthermia.
TWO ACTIONS OF γ‐AMINOBUTYRIC ACID ON THE RESPONSES OF THE ISOLATED BASILAR ARTERY FROM THE RABBIT
Authors: ANWAR N. , MASON D.F.J. 
Published: July 2012

In the isolated basilar artery of the rabbit, γ‐aminobutyric acid (GABA) (ED50±s.e.mean, 2.4 ± 1.1 × 10−5 m) produced a relaxation, if the tone had been increased with 5‐hydroxytryptamine (5‐HT).
3‐Aminoproprane sulphonic acid (3‐APS) produced a similar, but smaller relaxation, while baclofen had no effect. The relaxation produced by GABA was inhibited by bicuculline.
Transmural electrical stimulation produced a reproducible contraction of the isolated basilar artery. In 9 out of 14 preparations GABA (ED50± s.e.mean, 5.6 ± 2.1 × 10−7 m) caused a reduction of the response, with a maximum of 49.2 ±4.3%. Bicuculline did not inhibit these responses to GABA.
Baclofen (ED50±s.e.mean, 6.8± 1.4 × 10−7 m) produced a similar inhibition (47.4±3.2% maximum) but 3‐APS had no effect.
GABA (10−4 m) had no effect on the tone of isolated mesenteric or internal carotid arteries from the rabbit, whether or not the tone was increased with 5‐HT. Similarly, GABA (10−4 m) did not produce any change in the responses to transmural stimulation in isolated mesenteric or internal carotid arteries.
These findings are consistent with the presence of two types of GABA receptor on the rabbit basilar artery.
THE EFFECT OF ETHANOL ON INHIBITORY AND MOTOR RESPONSES IN THE RAT AND RABBIT ANOCOCCYGEUS AND THE BOVINE RETRACTOR PENIS MUSCLES
Authors: GILLESPIE J.S. , HUNTER J.C. , McKNIGHT A.T. 
Published: July 2012

Ethanol (200 mm) reduced the response to inhibitory nerve stimulation in the rat and rabbit anococcygeus and the bovine retractor penis (BRP) muscles. Ethanol also reduced the response to the inhibitory extract from the BRP consistent with the inhibitory factor in these extracts playing some part in the response to inhibitory nerve stimulation.
Ethanol's effect on the response to other inhibitory stimuli was examined in the rabbit anococcygeus and the BRP. In the anococcygeus the response to carbachol was reduced, to bradykinin and isobutylmethylxanthine (IBMX) unaltered, and to isoprenaline and adenosine 5′‐triphosphate (ATP) potentiated. In the BRP responses to IBMX and sodium nitroprusside were unaltered but in this tissue the response to isoprenaline was reduced. Ethanol's ability to reduce inhibitory responses is, therefore, selective and confined to inhibitory nerve stimulation, inhibitory extract, carbachol and, in the BRP, isoprenaline.
Ethanol reduced the rate of development of inhibition even where the magnitude of the inhibitory response was unaltered.
In the rat anococcygeus, ethanol (200 mm) potentiated the response to motor nerve stimulation and to noradrenaline (NA) at low frequencies and low concentrations respectively. Higher ethanol concentrations (400 mm) reduced the response to both motor nerve stimulation and NA. The motor response to carbachol was also reduced.
Ethanol (200 mm) itself caused an easily reversible contraction in all three tissues. This was not due to the release of NA but was highly sensitive to the removal of external calcium from the medium.
A unified explanation of these varied effects of ethanol based on a reduction in membrane binding of calcium and a reduced efficiency of receptor coupling is suggested.
EFFECTS OF OPIOIDS ON NONCHOLINERGIC EXCITATORY RESPONSES OF THE GUINEA‐PIG ISOLATED ILEUM: INHIBITION OF RELEASE OF ENTERIC SUBSTANCE P
Authors: GINTZLER ALAN R. , SCALISI JENNIE A. 
Published: July 2012

Experiments were carried out to determine whether opiates and opioid peptides could affect noncholinergic excitatory responses of the isolated guinea‐pig ileum.
Transmural field stimulation (10–20 Hz) of an atropine pretreated, intact segment of gut produced a contracture that could be elicited repeatedly without significant variation in magnitude.
This noncholinergic contracture was significantly reduced 75.3 ±8.3% (mean±s.e.mean) by tetrodotoxin (TTX; 1 μg/ml) and by desensitizing the preparation to substance P (76.3 ± 10.1%).
Morphine (5 × 10−6 m) as well as the opioid peptides d‐Ala2, N‐Phe4, Met‐(0)‐01 (FK 33–824; 9 × 10−7 m), d‐Met2‐Pro5 enkephalin (3 × 10−7 m) and d‐Ala2‐d‐Leu5‐enkephalin (5 × 10−6 m) inhibited the magnitude of the noncholinergic contracture but did not alter contractile responses to exogenous substance P (4 × 10−11 m‐4 × 10−10 m).
Pretreatment with the nicotinic receptor blocker, hexamethonium (10−5‐10−4 m) reduced by about 35% the magnitude of the atropine‐resistant contracture but did not affect inhibitory responses to morphine or opioid peptides. Thus the inhibition produced by morphine on the 20 Hz contracture does not involve a nicotinic cholinergic mechanism.
Naloxone pretreatment (10−6 m) in the presence of hexamethonium (10−5‐10−4 m) enhanced the magnitude of the noncholinergic contracture without affecting responses to exogenous substance P (4 × 10−11‐4 × 10−10 m).
These data suggest that substance P is the main, if not the sole, mediator of the atropine‐resistant 20 Hz contracture and indicate further that exogenous as well as endogenous opioids can modulate the release of this enteric peptide.
EFFECTS OF HARMALA ALKALOIDS ON TRANSMEMBRANE POTENTIALS OF GUINEA‐PIG PAPILLARY MUSCLES
Authors: CARPENTIER ROBERT G. 
Published: July 2012

The significance of the presence of a methoxy group in the 7 position of the indole nucleus of harmala alkaloids in terms of their effects on the action potential of cardiac muscle was analysed. Guinea‐pig papillary muscles were superfused with Tyrode solution at 30°C and exposed to harmine or its analogue harmane, in which the methoxy group has been removed from the molecule.
Harmine 2 × 10−5 m enhanced the amplitude of the action potential (AAP) of normal fibres and of slow responses elicited by noradrenaline in fibres depolarized by 21.6 mm K+‐Tyrode. The effect of harmine on AAP occurred in the absence of any change in membrane resting potential or maximum velocity of the upstroke and it was abolished by propranol. Harmane 2 × 10−5 m did not have any effect on normal action potentials and slow responses.
Higher concentrations of the two analogues depressed both AAP and the maximum velocity of the upstroke of the action potential, without affecting the duration of the action potential.
It is concluded that: (a) removal of the methoxy group from harmine (1) abolishes the catechol‐mediated stimulatory effect of a low concentration of the drug on the slow component of the upstroke of the action potential, and (2) does not modify the depressant effect of a high concentration of the drug. (b) The two analogues, harmine and harmane, do not affect the duration of the action potential of ventricular muscle.
SYNTHESIS OF NEW HALOPERIDOL ANALOGUES AND CHARACTERIZATION OF THEIR INTERACTIONS WITH α‐ADRENOCEPTORS IN RAT PAROTID SLICES AND HUMAN PLATELET MEMBRANES
Authors: ATLAS DAPHNE , FRIEDMAN ZEEV , LITVIN YAIR , STEER MICHAEL L. 
Published: July 2012

The synthesis of several butyrophenone analogues of haloperidol is described.
The effects of these compounds on α‐adrenoceptors were evaluated by examining their ability to reduce α1‐stimulated K+ release from rat parotid slices and to displace [3H]‐phentolamine from human platelet membrane α2‐adrenoceptors.
The affinity of haloperidol and its analogues for α1‐receptors was found to be 1 to 2 orders of magnitude greater than that for α2‐adrenoceptors. These observations suggest that most of the α‐adrenoceptor activity of butyrophenones results from their interaction with α1‐adrenoceptors.
The relatively high affinity of the butyrophenones for α1‐adrenoceptors suggests that they may be useful as probes in studies of α1‐adrenoceptors in these and other tissues.
THE EFFECTS OF ANAESTHETICS ON THE UPTAKE AND RELEASE OF AMINO ACID NEUROTRANSMITTERS IN THALAMIC SLICES
Authors: KENDALL T.J.G. , MINCHIN M.C.W. 
Published: July 2012

The effect of thiopentone, methohexitone, urethane and ketamine on the uptake and release of Y‐aminobutyric acid (GABA) and d‐aspartate by rat thalamic slices has been investigated.
A high, supra‐anaesthetic concentration of methohexitone increased the uptake of both d‐aspartate and GABA.
None of the anaesthetics used had any detectable effect upon the spontaneous release of either amino acid.
Urethane and ketamine had no effect upon the K+‐stimulated release of either amino acid.
Methohexitone and thiopentone produced a biphasic dose‐response on the K+‐stimulated release of both amino acids; low concentrations enhanced release, high concentrations depressed release.
Bicuculline hydrochloride and picrotoxin both significantly reduced the barbiturate‐induced enhancement of K+‐stimulated amino acid release, but did not significantly alter the depression of K+‐stimulated release at higher barbiturate concentrations.
Baclofen, either alone (1 μm to 1 mm), or tested against the barbiturates, had no detectable effect.
ACTIONS OF PROSTAGLANDIN F2αAND NORADRENALINE ON CALCIUM EXCHANGE AND CONTRACTION IN RAT MESENTERIC ARTERIES AND THEIR SENSITIVITY TO CALCIUM ENTRY BLOCKERS
Authors: GODFRAIND T. , MILLER R.C. 
Published: July 2012

The actions of prostaglandin F2α(PGF2α) and noradrenaline on contraction and45Ca exchange have been studied in rat mesenteric arteries.PGF2αand noradrenaline contracted rat isolated mesenteric artery preparations to about the same extent. The PGF2α‐stimulated contractions, unlike those produced by noradrenaline, were completely inhibited in calcium‐free physiological solution.The calcium entry blocking drugs, cinnarizine and flunarizine, had little effect on the resting exchange of calcium in the arterial smooth muscle, but inhibited PGF2α‐stimulated contractions and45Ca uptake to a similar extent.Flunarizine was about 7 fold more potent as an inhibitor of noradrenaline‐ than of PGF2α‐mediated contraction and45Ca uptake and this ratio was about 50 for cinnarizine.EGTA (1.25 mm) produced a relaxation of noradrenaline and PGF2α‐induced maximal contractions. Measured over the first 2 min of EGTA contact, the rate of relaxation was much faster in noradrenaline than in PGF2α‐stimulated preparations.Turnover of cellular calcium (influx plus efflux) during the first 2 min of noradrenaline contact was much greater than that produced by PGF2α, largely due to a greater effect of noradrenaline on calcium efflux.The results suggest that PGF2α‐ but not noradrenaline‐induced contractions are entirely dependent on the influx of extracellular calcium and that the agonists may stimulate calcium gating mechanisms differently.
PROSTACYCLIN CAN EITHER INCREASE OR DECREASE HEART RATE DEPENDING ON THE BASAL STATE
Authors: CHIAVARELLI M. , MONCADA S. , MULLANE K.M. 
Published: July 2012

The influence of the basal heart rate on the change in rate induced by prostacyclin (PGI2) was investigated in beagles anaesthetized with chloralose.
In male dogs with a low basal heart rate (<100 beats/min) PGI2, in doses up to 0.5 μg/kg intravenously, induced hypotension and tachycardia.
In contrast, PGI2‐induced hypotension was accompanied by bradycardia when either the basal heart rate was increased (> 130 beats/min) with isoprenaline or nitroprusside, or the dose of PGI2 was increased.
Female beagles were less sensitive than males to the stimulation of a reflex bradycardia by PGI2.
The influence of prostaglandin E2 (PGE2) and bradykinin on heart rate was also found to depend upon the basal state in some dogs.
Bilateral vagotomy reversed the bradycardia provoked by PGI2, PGE2 and bradykinin.
Thus, PGI2‐induced bradycardia is dependent on both the dose and the basal heart rate. Similarly the effects of PGE2 and bradykinin on heart rate also depend upon the basal state in some dogs. Moreover, there is a correlation between the ability of all three agonists to induce bradycardia, suggesting a common mechanism of action.
DIFFERENTIAL INHIBITION BY ADENOSINE OR BY PROSTAGLANDIN E1 OF HUMAN PLATELET AGGREGATION INDUCED BY ADENOSINE 5′‐O‐(1‐THIODIPHOSPHATE) AND ADENOSINE 5′‐O‐(2‐THIODIPHOSPHATE)
Authors: CUSACK N.J. , HOURANI S.M.O. 
Published: July 2012

Adenosine 5′‐diphosphate (ADP) induces human platelet aggregation and inhibits stimulated adenylate cyclase. Adenosine 5′‐O‐(1‐thiodiphosphate) (ADP‐α‐S) and adenosine 5′‐O‐(2‐thiodiphosphate) (ADP‐β‐S) act at the ADP receptor and achieve the same maximal rate of human platelet aggregation as each other. Adenosine and prostaglandin E1, which noncompetitively inhibit ADP‐induced aggregation by stimulating adenylate cyclase, inhibit aggregation induced by ADP‐α‐S more than aggregation induced by ADP‐β‐S. ADP‐α‐S, unlike ADP‐β‐S and ADP itself, does not inhibit stimulated adenylate cyclase. This suggests that the inhibition of stimulated adenylate cyclase by ADP, although not a cause of aggregation, may be of physiological importance in reducing the effects of endogenous agents such as adenosine and prostaglandins (for example, prostacyclin) to which the platelet may be exposed.Although the inhibition by ADP of adenylate cyclase cannot be the cause of aggregation, it could limit the inhibitory effects of agents such as PGE1 and adenosine which activate adenylate cyclase. The observation that PGE1 and adenosine are more powerful inhibitors of aggregation induced by vasopressin than by ADP (Haslam & Rosson, 1972), is consistent with this suggestion, although ADP and vasopressin do not act at the same receptor (Macfarlane & Mills, 1975). The differential effects on adenylate cyclase of ADP‐α‐S and ADP‐β‐S, which both act at the ADP receptor (Cusack & Hourani, 1981a,b), provides the first opportunity to investigate whether inhibition of adenylate cyclase by ADP receptor agonists can limit the effects on aggregation of inhibitors such as adenosine and PGE1.