bluuebunny/crossref_metadata_2025_split huggingface dataset:
HYPERPOLARIZATION OF RABBIT SUPERIOR CERVICAL GANGLION CELLS DUE TO ACTIVITY OF AN ELECTROGENIC SODIUM PUMP
Authors: LEES G.M. , WALLIS D.I. 
Published: July 2012

The mechanisms underlying the hyperpolarization which follows depolarization of rabbit superior cervical ganglion cells by acetylcholine, have been investigated and compared with the mechanisms responsible for the hyperpolarizations induced by orthodromic stimulation of the ganglion.
The amplitude of the drug‐induced hyperpolarization (after‐hyperpolarization) was diminished when [Na+]o and the duration of the preceding depolarization were reduced.
In K+‐free solutions, the amplitude of the after‐hyperpolarization was often diminished and its rate of development was reduced. In 12.5 mm K=+‐Krebs solutions, the amplitude and rate of development of the after‐hyperpolarization were increased; the potential was still present when the resting potential was at or close to EK.
Ouabain (10 μm) prevented or greatly diminished the after‐hyperpolarization. The rates of onset and decay of the after‐hyperpolarization were reduced in glucose‐free solutions.
It is, therefore, concluded that the after‐hypolarization is due to the activity of an electrogenic sodium pump.
The positive after‐potential associated with the ganglionic action potential was increased in K+‐free solutions and diminished when the resting potential approached EK, indicating that it is due to a period of increased K+ conductance. In the presence of high concentrations of hexamethonium (276 μm), the P wave was not selectively depressed by ouabain and has been shown by other workers to be due to a mechanism not involving an increased potassium conductance. It is concluded, therefore, that the positive after‐potential, the P wave and the after‐hyperpolarization are due to different mechanisms.
HYPERGLYCAEMIA PRODUCED BY THE POLYAMINES SPERMINE AND SPERMIDINE
Authors: ANDERSON D.J. , SHAW G.G. 
Published: July 2012

Intravenous injection of rabbits with the polyamines spermine (10–30 mg/kg) and spermidine (50–90 mg/kg) produced hyperglycaemia.
Given by intraventricular injection, spermine and spermidine gave rise to hyperglycaemia in doses 250–500 times smaller than those effective intravenously.
Intraventricular injections of the polyamines also produced hyperglycaemia in rats. Adrenal demedullation abolished the response.
In the rabbit, the hyperglycaemia resulting from intraventricular injection of polyamines was abolished in reserpine‐treated animals. Anaesthesia had no effect on the response unless accompanied by anoxia, when the response was potentiated.
Intracisternal injections of the polyamines in rabbits were less effective than intraventricular injections in that doses about four times larger were required to elicit an equivalent response.
EFFECT OF SELECTIVE PROTEOLYSIS ON THE ACCUMULATION OF 5‐HYDROXYTRYPTAMINE BY INTACT RAT BLOOD PLATELETS
Authors: SNEDDON J.M. , WILLIAMS K.I. 
Published: July 2012

The effect of perturbation of intact blood platelets with proteolytic enzymes was studied with respect to 5‐hydroxytryptamine (5‐HT) transport, adenine transport and intracellular Na+ and K+ levels.
Leucine aminopeptidase and thrombin reduced 5‐HT transport, released 5‐HT from pre‐labelled platelets and disturbed the gradient to monovalent cations. Leucine aminopeptidase, but not thrombin, inhibited adenine transport.
α‐Chymotrypsin and carboxypeptidases A and B were without effect on the parameters studied.
Trypsin selectively reduced 5‐HT transport. It did not release 5‐HT from blood platelets or inhibit adenine transport.
The action of proteolytic enzymes is discussed in terms of proteins localized in the external membrane that may function in part as membrane carriers.
FAILURE OF CHRONIC DENERVATION TO ALTER THE SENSITIVITY OF THE RAT DIAPHRAGM TO LOCAL ANAESTHETICS OR QUINIDINE
Authors: HARVEY S.C. , RANG H.P. 
Published: July 2012

The actions of procaine, nupercaine and quinidine on the membrane resting and action potentials of the normal and chronically denervated rat diaphragm were studied in vitro.
The degree of suppression of the rate of rise of the action potential by any of the drugs was the same in denervated as in normal muscle.
The degree of suppression of the rate of rise of the action potential by procaine in denervated muscle was about the same in the presence and absence of tetrodotoxin.
Three possible interpretations of the lack of effect of denervation on the response to these drugs are discussed:

In the sodium channel, the structural alteration that confers resistance to tetrodotoxin is quite limited and does not affect groups which interact with local anaesthetics.
Local anaesthetics are non‐selective in their binding so that alteration in membrane structure around the channel has little influence on the efficiency of the local anaesthetic.
Denervation may affect the outer surface of the membrane, where acetylcholine and tetrodotoxin act, more than the intracellular surface, where local anaesthetics appear to act.

The slope of the log concentration‐effect line for quinidine was steeper than that for procaine or nupercaine.
MORPHINE ANALGESIA AND THE BULBOSPINAL NORADRENERGIC SYSTEM: INCREASE IN THE CONCENTRATION OF NORMETANEPHRINE IN THE SPINAL CORD OF THE RAT CAUSED BY ANALGESICS
Authors: SHIOMI H. , TAKAGI H. 
Published: July 2012

Administration of an analgesic dose (10 mg/kg, s.c.) of morphine increased the concentration of a noradrenaline metabolite, normetanephrine (NM) in the spinal cord of normal rats. The time course of the change in the NM concentration corresponded approximately to that of the morphine analgesia. The concentration of noradrenaline was not affected.
A similar effect on the NM concentration was also observed after the administration of pentazocine (30 mg/kg, s.c.) and nalorphine (20 mg/kg, s.c.).
The NM increasing effect of morphine, pentazocine and nalorphine was found in the dorsal half of the spinal cord but not in the ventral half.
The increase in the concentration of NM induced by morphine, pentazocine or nalorphine was completely suppressed by naloxone (1 mg/kg, s.c.) given 5 min before the administration of these drugs.
When the spinal cord was transected at C1, the NM increasing effect of morphine disappeared, yet when the brain stem was transected at the inter‐collicular level, the effect remained.
In morphine‐tolerant rats, the concentration of NM in the spinal cord was almost the same as that observed in normal rats, but the increase in the concentration of NM in the spinal cord after the acute administration of morphine did not take place.
The NM concentration in the spinal cord of normal rats was not modified by aminopyrine (75 mg/kg, s.c.), chlorpromazine (10 mg/kg, s.c.), mephenesin (100 mg/kg, i.p.) or naloxone (25 mg/kg, s.c.).
The possible relation between morphine analgesia and the descending noradrenergic neurones in the spinal cord of rats is discussed.
THE EFFECT OF ETHACRYNIC ACID ON THE GUINEA‐PIG AND RAT ISOLATED VAS DEFERENS
Authors: KHOYI M.A. , POUSTI A. , ZARRINDAST M.R. 
Published: July 2012

The effect of ethacrynic acid (EA) was studied on guinea‐pig and rat vas deferens in vitro.
EA contracted the guinea‐pig but not the rat vas deferens in a dose‐dependent manner (50–800 μg/ml). Tyramine caused contraction in 10 out of 18 guinea‐pig vas deferens; EA caused contraction in 17 of the preparations which did not respond to tyramine. Repeated doses of EA produced tachyphylaxis, but there was no cross tachyphylaxis to tyramine.
The contractions produced by EA were prevented by phentolamine or reserpine pretreatment and potentiated by cocaine. A low concentration of desipramine (3 ng/ml) potentiated and higher concentrations (0.6 and 3.0 μg/ml) inhibited the response of vas deferens to EA.
Hexamethonium (100 μg/ml) or atropine (0.1 μg/ml) did not inhibit the effect of EA, excluding the nicotinic and muscarinic receptors as the sites of action.
The effect of noradrenaline (NA) on the guinea‐pig and rat vas deferens was enhanced by EA pretreatment, which may be due to inhibition of NA uptake.
It is concluded that EA releases NA from guinea‐pig vas deferens. The mechanism of release seems to be different from that of tyramine.
EFFECT OF DRUGS ON RAT PAW OEDEMA INDUCED BY MERCURY
Authors: JINDAL M.N. , KELKAR V.V. , VAISHNAV U.H. 
Published: July 2012

Metallic mercury (0.04 ml) injected into the foot pad of rats induced a consistent inflammatory reaction, which at 4 h showed oedema but no cellular infiltration or vascular changes. The lesions exhibited lymphocytic infiltration, vasodilatation and haemorrhages at 24 and 48 h, and often became cystic after 2–3 weeks, before healing. The oedema volume at 4 h was used to test anti‐inflammatory activity of drugs.
Cortisone, phenylbutazone, indomethacin, acetylsalicylic acid, flufenamic acid and propranolol exhibited potent, dose‐related anti‐inflammatory activity. Aminopyrine, chloroquine and chlorpromazine were only moderately effective. Dimercaprol, adrenaline, and to some extent, mepyramine also inhibited mercury‐induced oedema.
This simple model of acute inñammation may be useful for preliminary tests of anti‐inflammatory activity.
THE ACTION OF NITROGLYCERINE AND DIPYRIDAMOLE IN NORMAL AND ISCHAEMIC DOG HEART
Authors: GRAYSON J. , SCOTT C. 
Published: July 2012

Network and post‐network resistances were measured together with heat clearance and heat production in the myocardium.
Nitroglycerine dilated all resistance vessels but was twice as effective on network as compared with post‐network vessels.
Dipyridamole dilated network and post‐network vessels equally.
Nitroglycerine had no effect on heat clearance or heat production in ischaemic myocardium.
Dipyridamole increased heat clearance in normal but not in ischaemic myocardium.
Dipyridamole depressed heat production in normal and ischaemic myocardium.
That the clinical effectiveness of nitroglycerine does not depend entirely on its coronary vasodilator properties is confirmed.
It is suggested that the action of dipyridamole in depressing myocardial heat production may be due to an action on the efficiency of oxygen utilization during cardiac contraction.
THE EFFECT OF VARIOUS AMINE‐DEPLETING DRUGS ON THE FEVER RESPONSE EXHIBITED BY RABBITS TO BACTERIAL OR LEUCOCYTE PYROGEN
Authors: METCALF G. , THOMPSON J.W. 
Published: July 2012

The concentration of noradrenaline, dopamine and 5‐hydroxytryptamine (5‐HT) in the rabbit brainstem was measured during fevers produced by either an injection of bacterial pyrogen (BP) or continuous infusion of leucocyte pyrogen (LP).
Both procedures had little effect on the concentration of noradrenaline in the preoptic/hypothalamic area but significantly (P < 0.001) lowered the concentration of noradrenaline in the midbrain and pons/medulla.
BP significantly (P < 0.01) lowered the concentration of 5‐HT in the preoptic/hypothalamic area but had no effect in the midbrain or pons/medulla, whereas LP significantly (P < 0.01) lowered the concentration of 5‐HT in the midbrain and pons/medulla but had little effect in the hypothalamus.
The concentration of dopamine throughout the brainstem was little affected by either BP or LP fevers. However the concentration in the midbrain was significantly reduced by LP (P < 0.001).
α‐Methyltyrosine (200 mg/kg) pretreatment diminished the pyrogenic response to both BP and LP whilst p ‐chlorophenylalanine (300 mg/kg) slightly enhanced the response to both forms of challenge.
Reserpine (1 mg/kg) diminished both types of fever whilst a combination of α‐methyltyrosine and p ‐chlorophenylalanine slightly enhanced the fevers produced by either BP or LP.
The results obtained are discussed in relation to the mechanisms involved in the production of fever and to the possible function of noradrenaline and 5‐HT as thermoregulatory transmitters.
THE PREVENTION BY SULPHYDRYL COMPOUNDS OF THE TOXICITY IN THE CAT OF 2,6‐DIMETHOXYPHENOL AND ITS MORPHOLINOPROPIONYL ESTER
Authors: LOVELESS A.H. , MAXWELL D.R. 
Published: July 2012

Intravenous (—)‐2,6‐dimethoxyphenyl‐2‐morpholinopropionate hydrochloride (M&B 16,573) produced anaesthesia of short duration in the mouse, rat, rabbit, cat, dog and monkey. In the cat but not in other species, a severe and usually fatal toxic reaction was seen 1‐2 h after administration.
This toxic reaction but not the anaesthetic properties of M&B 16,573 was prevented by the intravenous administration of cysteine or N‐acetylcysteine. Cysteamine or dimercaprol were ineffective.
Intravenous administration of 2,6‐dimethoxyphenol or 2,6‐dimethoxyquinol in the cat produced a response similar to the delayed toxic effects of M&B 16,573 but not preceded by anaesthesia. The toxic effects of these compounds were prevented by cysteine.
Intravenous 4‐allyl‐2,6‐dimethoxyphenyl‐2‐morpholinoprop*ionate hydrochloride produced anaesthesia in the cat without the delayed toxic effects seen after M&B 16,573.
The acute toxicity of 2,6‐dimethoxyquinol in mice was reduced by the administration of cysteine or N‐acetylcysteine.
It is postulated that the delayed effects produced by M&B 16,573 in the cat are due to the formation of 2,6‐dimethoxyquinol and 2,6‐dimethoxybenzoquinone in this species, the toxicity of the latter being reduced by sulphydryl compounds.
EFFECT OF ANTI‐INFLAMMATORY DRUGS ON THE MEMBRANE POTENTIAL OF VASCULAR ENDOTHELIAL CELLS in vitro
Authors: NORTHOVER B.J. 
Published: July 2012

Cells of the aortic endothelium isolated from the guinea‐pig and bathed at 37° C with a calcium‐free superfusion fluid had membrane potentials of −41 ± 7 mV (mean ± s.e. mean).
Depolarization was produced by addition of potassium (50‐200 mM) or certain other monovalent metal cations to the superfusion fluid. Depolarization was rapidly reversed on return to the original superfusate.
Several divalent metal cations, notably calcium (16 mM), caused depolarization which was only slowly and incompletely reversed on return to the original calcium‐free superfusate.
Repolarization after exposure to calcium was accelerated and made more complete by addition of indomethacin (0.25 mM) to the superfusate.
The trivalent cations of lanthanum, aluminium or iron (0.1 mM) inhibited the depolarizing effect of calcium (16 mM).
Exposure to histamine (100 μg/ml) or heating to 45° C for 1 h caused depolarization in the presence but not in the absence of calcium. Subsequent removal of histamine or cooling again to 37° C in the continued presence of calcium permitted only slow and partial repolarization. However, repolarization was more rapid and complete in the presence of indomethacin (0.25 mM).
Heating to 45° C for 5 h in the presence of calcium caused progressive and almost complete depolarization. Lanthanum, cinchocaine, indomethacin, flufenamic, meclofenamic and salicylic acids, phenylbutazone and aminopyrine each reduced the depolarization, but hydrocortisone, chloroquine, benzindamine, isoprenaline and aminophylline did not.
THE EFFECTS OF BURIMAMIDE AND METIAMIDE ON BASAL GASTRIC FUNCTION IN THE CAT
Authors: HARRIS D. W. , SMY J.R. , REED J.D. , VENABLES C.W. 
Published: July 2012

Burimamide injected intravenously in the anaesthetized or conscious cat produced significant increases in gastric acid secretion: in the anaesthetized cat it produced increased gastric mucosal blood flow.
Metiamide, in doses which inhibited pentagastrin‐stimulated acid secretion, produced no increase in gastric acid secretion in conscious animals, or gastric acid secretion or gastric mucosal blood flow in the anaesthetized cat.
Metiamide did not influence the amount of acid which diffused out of the stomach when instilled at pH values between 1.5 and 6.0.
The possible mode of action of burimamide in increasing basal gastric secretion is discussed.
THE FAILURE OF p‐CHLOROPHENYLALANINETO AFFECT VOLUNTARY ALCOHOL CONSUMPTION IN RATS
Authors: HOLMAN R.B. , HOYLAND VALERIE , SHILLITO ELIZABETH E. 
Published: July 2012

The effects of p‐chlorophenylalanine (PCPA) administered orally and intraperitoneally on rat brain 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) content were compared. The depletion of brain 5‐HT and 5‐HIAA following PCPA (316 mg/kg) injected intraperitoneally every third day was not significantly different from that following the administration of PCPA (316 mg/kg) by stomach tube on eight consecutive days.
Rats tested for alcohol preference before, during and after treatment with PCPA on two intraperitoneal dose regimens (either 316 mg/kg then 100 mg/kg four days later or 316 mg/kg three times at intervals of three days) showed no reduction in voluntary alcohol consumption.
The results indicated that depletion of brain 5‐HT and 5‐HIAA is not responsible for the reduction of voluntary alcohol intake which has been reported to follow chronic oral administration of PCPA to the rat (Myers & Veale, 1968). The possibility of a learned aversion to alcohol due to an association with PCPA administration is discussed.
PROSTAGLANDIN RELEASE FROM CAT AND DOG SPLEEN
Authors: BEDWANI J.R. , MILLAR G.C. 
Published: July 2012

The output of prostaglandins from the spleens of cats and dogs was studied. Comparison is made between the results found in the two species.
The release of prostaglandins was investigated in isolated saline‐perfused spleens and in incubates of spleen slices. Release in response to nerve stimulation, and exposure to adrenaline or noradrenaline was compared with resting release.
A resting release of prostaglandins was found in the dog but not in the cat spleen.
Whereas stimulated dog spleens released microgram quantities of prostaglandins E2 and F2α, prostaglandin output from the cat spleen under similar conditions was undetectable or barely detectable.
The identity of the prostaglandins released from the dog spleen (prostaglandins E2 and F2α) was confirmed by mass spectrometry.
The species difference in prostaglandin output from the spleen is discussed in relation to the hypothesis that endogenous prostaglandins modify the responses of this organ to nervous stimuli.
DISPLACEMENT BY METIAMIDE OF THE DOSE‐RESPONSE CURVES TO PENTAGASTRIN AND METHACHOLINE IN THE CONSCIOUS RAT
Authors: LUNDELL L. 
Published: July 2012

The effect of a specific histamine H2‐receptor antagonist, metiamide, on the acid dose‐response curves for pentagastrin or methacholine was studied in rats provided with Heidenhain pouches.
Metiamide induced a shift to the right of the dose‐response curve to pentagastrin and lowered the maximal secretion.
In contrast, metiamide only increased the ED50 for methacholine but did not alter the calculated maximal response.
The effect of metiamide on pentagastrin and methacholine‐induced secretion is in agreement with the previously suggested difference in the part played by mucosal histamine in the mode of action of the two stimulatory agents.
DUAL EFFECT OF α‐ADRENOCEPTOR ANTAGONISTS IN RAT ISOLATED VAS DEFERENS
Authors: JURKIEWICZ A. , JURKIEWICZ N.H. 
Published: July 2012

In rat isolated vas deferens, the isotonic contractile responses to low doses of noradrenaline or adrenaline were antagonized, and those to high doses were potentiated, by yohimbine, piperoxan, phentolamine and tolazoline. Effects due to intermediate doses were not affected, or were potentiated within about 30 min, following an initial inhibition.
The α‐adrenoceptor blockers thus caused a shift to the right and an increase of the maximum height of log dose‐response curves of α‐adrenoceptor stimulants. For a given dose of antagonist, the onset was slower for the potentiating than for the blocking effect.
The shift to the right induced by piperoxan and yohimbine on dose‐response curves of noradrenaline and adrenaline was analysed with the Schild plot, and the slopes obtained, around 0.3, were lower than expected from receptor theory. When cocaine was used to block neuronal uptake, the slopes were close to 1.0.
The increase in maximum response to noradrenaline and adrenaline induced by α‐adrenoceptor blockers was dependent on the time of incubation, on the dose of antagonist, and on the initial height of responses to the agonist. A less pronounced potentiation was also obtained when acetylcholine was used as agonist.
The findings are explained in terms of receptor theory as being due to a dual effect of α‐adrenoceptor antagonists; competitive antagonism proper, which may be disclosed after blockade of neuronal uptake, and an interaction at a different locus, which results in potentiation of the effects of noradrenaline and adrenaline.
A COMPARISON OF THE TIME COURSE OF EXCITATION AND INHIBITION BY IONTOPHORETIC DECAMETHONIUM IN FROG ENDPLATE
Authors: ADAMS P.R. 
Published: July 2012

The depolarization of frog endplate by a brief iontophoretic application of decamethonium was slower in time course than the inhibition of a long carbachol response produced by the same decamethonium pulse, or than the excitation produced by a brief equipotent carbachol pulse.
The delay between the peak inhibition and peak excitation produced by decamethonium, about 50 ms, is too great to be explained by slow receptor activation kinetics, since Katz & Miledi (1973) have shown that the lifetime of decamethonium‐activated receptors is only 0.25 milliseconds.
If doses of carbachol and decamethonium are adjusted to give response amplitudes in the ratio corresponding to the ratio of their presumed maximum responses, then there is little difference in the time courses of the responses.
This observation, together with the finding that increasing the dose applied slows the decamethonium response much more than the carbachol response, suggests that a decamethonium response contains contributions from a much wider area of receptive membrane than does a carbachol response of equal amplitude.
Simulation shows that these geometrical effects are sufficient to account for the rapidity of inhibition compared to excitation without postulating slow receptor kinetics.
It is pointed out that similar effects may account for certain results obtained in iontophoretic studies of desensitization.