bluuebunny/crossref_metadata_2025_split huggingface dataset:
HYPERTHERMIC EFFECTS OF MORPHINE: SET POINT MANIPULATION BY A DIRECT SPINAL ACTION
Authors: RUDY T.A. , YAKSH T.L. 
Published: July 2012

Rats were implanted with chronic indwelling catheters in the lumbar spinal subarachnoid space in order to study the effects of morphine on body temperature.
Morphine administered intrathecally produced a dose‐dependent rise in body temperature that was antagonized by naloxone.
The rise in body temperature evoked by a given dose of morphine appeared to be independent of the environmental temperature (4°C to 32°C) and was consistently associated with coordinated thermoregulatory responses (i.e. shivering and tail vasoconstriction). The fall in body temperature observed in these hyperthermic animals, following naloxone, was associated with a vasodilatation which coincided with the fall to the premorphine temperature level.
Morphine administered systemically also produced hyperthermia. This was only partially reversed by intrathecal naloxone. In animals made tolerant to the hyperthermic effects of systemic morphine, the intrathecal administration of naloxone produced a fall in body temperature.
Naloxone alone, administered either intrathecally or systemically, had no effect upon body temperature.
We suggest that morphine exerts a direct, pharmacologically specific effect on the spinal cord, which results in an altered thermoregulatory set point in the rat.
SUBCELLULAR DISTRIBUTION OF ETORPHINE IN RAT BRAIN AND EVIDENCE FOR in vivo STEREOSPECIFIC BINDING
Authors: CERLETTI CHIARA , COCCIA P. , MANARA L. , MENNINI TIZIANA , RECCHIA M. 
Published: July 2012

Control experiments were carried out by homogenizing rat brain at 0°C with sucrose containing various concentrations of [3H]‐etorphine. Subcellular fractionation of this homogenate showed that the distribution of the labelled drug amongst the primary fractions was dependent on the concentration of etorphine in the homogenate.
Rats were injected intravenously with 0.2 and 20 μg/kg of [3H]‐etorphine. The brains were homogenized and fractionated in sucrose containing 4.2 times 10−5 M unlabelled etorphine in order to control redistribution artifacts. Different distribution profiles in the subcellular fractions were observed at these two dose levels.
Concurrent administration of either cyprenorphine or naloxone with intravenous etorphine, caused a shift of the labelled drug from the P3 fraction to the supernatant fraction.
The subcellular distribution of intravenously administered [3H]‐etorphine was also studied by homogenizing brains in etorphine‐free sucrose, and sucrose containing either levorphanol or dextrorphan. From these experiments it was concluded that the P3 microsomal fraction is a major site to which in vivo etorphine is stereospecifically bound in the rat brain.
THE EFFECTS OF REPLACING ESTER BY AMIDE ON THE BIOLOGICAL PROPERTIES OF COMPOUNDS RELATED TO ACETYLCHOLINE
Authors: BARLOW R.B. , BREMNER J.B. , SOH K.S. 
Published: July 2012

Replacement of ester by amide in series of derivatives of diphenylacetic acid reduces the affinity for muscarine‐sensitive. acetylcholine receptors of the guinea‐pig ileum from 40‐ to 100‐fold. With similar series of phenylacetic acid the reduction is only 2‐ to 4‐fold. In both series changes in the composition of the onium group produce similar changes in the affinity of amides and esters and it appears that the stiffness of the amide bond reduces the binding of the phenyl groups at the far end of the molecule from the onium atom.
Replacement of ester by amide in similar series of acetyl compounds reduces activity on the guinea‐pig ileum over 1000‐fold and on the frog rectus over 50‐fold. Compounds with larger onium groups are antagonists on both preparations with log affinity constant around 3. The amides have similar affinity for electric eel acetylcholinesterase.
The amides are slightly bigger than the esters in solution and slightly more hydrophilic.
Replacement of ester by amide in acetylcholine reduces the proportion of gauche conformer about the C—C—bond from 100% to 39%.
The ability of acetylcholine to activate receptors is thought to depend on some degree of flexibility in the —CO—O— bond, though the hydration of the bond may also be important.
THE CARDIOVASCULAR EFFECTS OF CYCLOPROPANE IN THE INTACT, DECEREBRATE AND PITHED RABBIT PREPARATIONS
Authors: HUGHES R.L. , MACKENZIE J.E. 
Published: July 2012

The anaesthetic cyclopropane was given to intact, decerebrate and pithed unanaesthetized rabbit preparations to determine the relative importance in vivo of its central and peripheral cardiovascular effects.
Cyclopropane elevated both the heart rate and the mean arterial pressure in the intact rabbit.
In the decerebrate rabbit, cyclopropane elevated the heart rate and efferent cervical preganglionic nerve activity and diminished the magnitude of these components of the aortic baroreceptor reflex, the mean arterial pressure being unaffected.
Apart from slight myocardial depression, cyclopropane was largely without effect in the pithed rabbit.
It is concluded that cyclopropane produces its cardiovascular effects by supra‐collicular activation eliciting an elevation of mean arterial pressure, a central sub‐collicular activation producing an increase in heart rate, and that in vivo the peripheral effects of cyclopropane are of minimal importance in comparison to these central effects.
REVERSAL OF GUANETHIDINE BLOCKADE OF SYMPATHETIC NERVE TERMINALS BY TETRAETHYLAMMONIUM AND 4‐AMINOPYRIDINE
Authors: KIRPEKAR MADHURI , KIRPEKAR S.M. , PRAT J.C. 
Published: July 2012

The effect of tetraethylammonium (TEA) and 4‐aminopyridine (4‐AP) on the inhibitory effect of guanethidine on noradrenaline (NA) release was investigated in the perfused spleen of the cat.
Guanethidine blocked the release of NA evoked by nerve stimulation. TEA and 4‐AP readily reversed this inhibitory effect, and the NA output was nearly doubled after repeated stimulation of the nerves. On subsequent perfusion with Krebs solution without TEA or 4‐AP, the inhibitory effect of guanethidine reappeared
The reversal of guanethidine blockade of sympathetic nerves by TEA and 4‐AP is discussed.
THE EFFECT OF THE IONOPHORES X‐537A AND A23187 ON THE NORADRENALINE OUTPUT FROM PERIPHERAL ADRENERGIC NEURONES IN THE PRESENCE OF VARIOUS DIVALENT CATIONS
Authors: ITO S. , NAKAZATO Y. , OHGA A. 
Published: July 2012

The effects of the ionophores, X‐537A and A23187 on the noradrenaline output from peripheral adrenergic neurones of isolated vas deferens of the guinea‐pig were investigated in the presence of various divalent cations.
X‐537A (17 μM) caused an increase in the noradrenaline output in the presence of barium, calcium and strontium. The effectiveness of the cations was Ba > Ca ≥ Sr.
In the absence of calcium and in the presence of ethyleneglycol‐bis(2‐aminoethylether)‐N, N, N′, N′,‐tetraacetic acid (EGTA, 1 mM), the response was reduced by about 50% of that obtained in the presence of calcium.
Calcium was the most effective cation in stimulating noradrenaline output when reintroduced after pretreatment with A23187 (191 μM). The response increased in an almost linear fashion with the concentration of calcium 1 mM to 10 mM.
Excess magnesium (20 mM) reduced the response induced by X‐537A in the presence of barium. However, it was without effect on the response produced by reintroduction of calcium after pretreatment with A23187.
The response induced by X‐537A in the presence of barium increased with an increase in the concentration of external sodium from 25 mM to 143 mM.
It is suggested that X‐537A may cause an increase in the noradrenaline output by depolarization as well as by transferring cations as an ionophore. On the other hand, A23187 may produce an increase in the noradrenaline output, transferring calcium across the membrane as a specific calcium ionophore.
THE EFFECTS OF GLYCEROL DETUBULATION, OF MANGANESE IONS, OF DANTROLENE AND OF NITRATE IONS ON THE RESPONSES OF ISOLATED CHRONICALLY DENERVATED SOLEUS MUSCLES OF THE MOUSE TO ACETYLCHOLINE
Authors: HALL MOIRA T. , MALEQUE M.A. , WADSWORTH R.M. 
Published: July 2012

In the isolated chronically denervated soleus muscle of the mouse acetylcholine produced a biphasic contraction.
In muscles detubulated by glycerol treatment, the first phase of the acetylcholine contraction was almost abolished, but the second was only slightly reduced or was unaffected.
Manganese ions (10 mM) reduced the first phase of the acetylcholine response, but enhanced the second.
Dantrolene sodium (5.94 times 10−5 M) reduced the first phase of the acetylcholine response, but not the second.
Nitrate ions (118 mM) augmented the first phase but not the second.
It was concluded that the first phase requires the excitation‐contraction‐coupling sequence: membrane depolarization‐T‐tubules‐Ca2+ release from sarcoplasmic reticulum. In contrast, the second phase appears to occur independently of these processes.
EVIDENCE FOR THE ROLE OF ADRENOCORTICAL HORMONES IN THE REGULATION OF NORADRENALINE AND DOPAMINE METABOLISM IN CERTAIN BRAIN AREAS
Authors: RASTOGI R.B. , SINGHAL R.L. 
Published: July 2012

Bilateral adrenalectomy suppressed body growth and increased the activity of tyrosine hydroxylase in rat striatum in a time‐dependent manner. Fifteen days after adrenalectomy, the concentrations of noradrenaline were decreased significantly in hypothalamus and striatum, as were those of dopamine in brain stem and striatum.
Catechol‐O‐methyltransferase failed to change in response to adrenalectomy, but the activity of monoamine oxidase in cortex was significantly increased 7 days after surgery. These changes in various neurochemical parameters were even more pronounced 15 days after adrenal ablation.
Administration of corticosterone (10 mg/kg i.p.) to adrenalectomized rats effectively reversed the observed effects on brain amine metabolism. Corticosterone treatment for 7 days beginning from the 8th day of adrenalectomy virtually restored the concentrations of noradrenaline and dopamine as well as the activities of striatal tyrosine hydroxylase and cerebrocortical monoamine oxidase to the values seen for sham‐operated controls.
Our data suggest that changes seen in brain noradrenaline and dopamine of adrenalectomized rats are specific to adrenocortical steroids and that these hormones play a role in the regulation of catecholamine formation.
EFFECTS OF MINOXIDIL AND NITROPRUSSIDE ON REFLEX INCREASES IN MYOCARDIAL CONTRACTILITY
Authors: ROBIE N.W. 
Published: July 2012

The effects of nitroprusside and minoxidil on increases in myocardial contractility resulting from carotid artery occlusion were investigated in anaesthetized dogs. The results were compared with those produced by intravenous influsion of noradrenaline.
Nitroprusside and minoxidil attenuated the pressor responses produced by carotid artery occlusion.
Nitroprusside, but not minoxidil, attenuated the maximal myocardial contractility resulting from carotid occlusion.
The pressor and contractility responses to noradrenaline infusion were unaffected by either agent.
Nitroprusside failed to alter the myocardial responses produced by dimethylphenylpiperazinium.
These results, in conjunction with those of other investigators who have demonstrated that nitroprusside does not affect the release of noradrenaline from adrenergic neurones, suggest that nitroprusside may inhibit sympathetic nervous system reflex activity via an afferent and/or central component.
EFFECTS OF MONOCROTALINE PRETREATMENT OF RATS ON REMOVAL OF 5‐HYDROXYTRYPTAMINE AND NORADRENALINE BY PERFUSED LUNG
Authors: GILLIS C.N. , HUXTABLE RYAN J. , ROTH ROBERT A. 
Published: July 2012

The alkaloid, monocrotaline, causes significant pulmonary damage in many species, including the rat. We, therefore, determined whether the inactivation of biogenic amines by perfused lungs of rats was modified by prior treatment of the animals with monocrotaline.
Young rats (45 to 50 g) treated for 21 days with monocrotaline (22 μg/ml) in their drinking water developed right ventricular hypertrophy. Treated animals gained weight more slowly and consumed less food and water than control rats that drank tap water. Lungs from monocrotaline‐treated animals were heavier and had a higher protein content than control lungs.
Isolated lungs from treated animals removed and metabolized 50% less perfused 5‐hydroxytryptamine than did controls.
The diminished 5‐hydroxytryptamine metabolism was probably due to impaired delivery of substrate to intrapulmonary monoamine oxidase (MAO) since MAO activity in 600 g supernatant fractions of homogenates of lungs from monocrotaline‐treated rats was not different from control values.
Pulmonary removal of perfused noradrenaline was decreased about 60% by the 21‐day treatment, suggesting that the effects of monocrotaline were somewhat nonspecific.
These effects were not caused by monocrotaline directly, since perfusion of lungs from untreated animals with this drug did not alter removal of co‐perfused 5‐hydroxytryptamine.
Reduced pulmonary removal of circulating biogenic amines following pretreatment with monocrotaline may reflect damage to capillary endothelium, which could also affect other metabolic functions of lung.
THE LOCAL ANAESTHETIC ACTIVITY OF A BENZOTRIAZINIUM SALT
Authors: FRENCH A.M. , KHAN M.T. , SCOTT N.C. 
Published: July 2012

The local anaesthetic properties of 2‐w‐propyl‐4‐p‐tolylamino‐1,2,3‐benzotriazinium iodide (TnPBI) were compared with those of lignocaine hydrochloride on intact and desheathed sciatic nerves of the frog, on the phrenic nerve‐hemidiaphragm preparation of the rat, and by the intradermal wheal test in the guinea‐pig.
Both TnPBI and lignocaine were more potent* on desheathed than on intact sciatic nerves. The potency of TnPBI was affected more than that of lignocaine by the presence of the sheath in intact nerves.
Both drugs inhibited conduction in the rat phrenic nerve, as shown by the reduction in twitch tension of the diaphragm elicited by nerve stimulation. TnPBI also caused an initial augmentation of the twitch tension of the diaphragm when applied directly to the muscle.
TnPBI was shown to be approximately twice as potent as lignocaine by the guinea‐pig intradermal wheal test.
These results are discussed in view of the known effects of TnPBI on intracellular calcium storage.
PRESYNAPTIC ACTIONS OF β‐AMINOBUTYRIC ACID AND SOME ANTAGONISTS IN A SLICE PREPARATION OF CUNEATE NUCLEUS
Authors: SIMMONDS M.A. 
Published: July 2012

A slice preparation of the rat cuneate nucleus is described which is suitable for electrophysiological studies on the presynaptic action of drugs.
Superfusion of a slice with γ‐aminobutyric acid (GABA) depolarized the afferent nerves in a concentration‐related manner. The responses were CI “‐dependent. Depolarizations to high concentrations of GABA often faded. Glycine and l‐glutamate had little effect.
(‐h)‐Bicuculline antagonized GABA in an apparently competitive manner (pA2 = 5.35) at low response levels. Strychnine was 10 times less potent. Responses to high concentrations of GABA were sometimes potentiated by (+)‐biculline and strychnine.
Bemegride and leptazol both antagonized GABA, but with low potency and in a manner which was clearly not competitive.
BRAIN TRYPTOPHAN METABOLISM ON THE 5‐HYDROXYTRYPTAMINE AND KYNURENINE PATHWAYS IN A STRAIN OF RATS WITH A DEFICIENCY IN PLATELET 5‐HT
Authors: JOSEPH MICHAEL H. 
Published: July 2012

Brain 5‐hydroxytryptamine (5‐HT) metabolism has been compared in albino (Sprague‐Dawley; SD) and in Fawn‐Hooded (FH) rats, which have an inherited platelet 5‐HT deficiency.
It was confirmed that blood 5‐HT levels in the FH rats were about one quarter of those in the SD rats.
Brain 5‐HT and 5‐HIAA were however higher in FH rats on a per gram basis; there was no difference between the strains on a per brain basis, because of the smaller brain weights of the FH rats.
Brain and plasma tryptophan were not significantly different in the two strains. Plasma kynur‐enine was higher in the FH rats, and brain kynurenine was also higher either on a per gram or on a per brain basis.
The reserpine‐releasable brain 5‐HT was the same proportion of total brain 5‐HT in the two strains.
Experiments with pargyline suggested that the turnover of 5‐HT was somewhat higher in the FH rats on a per gram basis, but not significantly so on a per brain basis.
It is concluded that although brain tryptophan metabolism may be somewhat accelerated along both the 5‐HT and kynurenine pathways in the FH rats there is no gross deficiency in the binding of 5‐HT in their brains analogous to that found in their platelets.
THE EFFECTS OF ACETYLCHOLINE ON THE MEMBRANE AND CONTRACTILE PROPERTIES OF SMOOTH MUSCLE CELLS OF THE RABBIT SUPERIOR MESENTERIC ARTERY
Authors: KURIYAMA HIROSI , SUZUKI HIKARU 
Published: July 2012

Effects of acetylcholine (ACh) on the membrane potential and mechanical properties of rabbit superior mesenteric artery were investigated by the use of microelectrode and isometric tension recording methods. The membrane potential was −62.5 ± 3.0 mV (s.d.). The maximum slope of the membrane depolarization produced by tenfold increase in [K]0 plotted on a log scale was 48 mV. Excess [K]0 and low [K]0 depolarized the membrane and produced contraction (contracture). The minimum depolarization to produce contraction was 10 mV.
Low concentrations (10 and 100 ng/ml) of ACh hyperpolarized the membrane. Increased concentrations of ACh (1 and 10 μg/ml) hyperpolarized the membrane further in adult rabbit, while increased concentrations of ACh produced a smaller hyperpolarization in young rabbit. These potential changes produced by ACh in immature and adult rabbits were suppressed by treatment with atropine (0.1 μg/ml).
ACh (10 ng to 1 μg/ml) consistently generated contraction in Krebs solution. However, ACh relaxed the contraction induced by either K+ or noradrenaline in the adult rabbit, and it enhanced contraction produced by this treatment in the immature rabbit. In Ca‐free EGTA solution, the action of ACh on the mechanical response was markedly suppressed, although high concentrations of ACh still evoked contraction. However, treatment with atropine (1 μg/ml) completely prevented these actions of ACh.
ACh‐induced relaxation during either K+‐induced or noradrenaline‐induced contraction was not caused by the hyperpolarization of the membrane.
It is concluded that ACh possesses dual actions on smooth muscle cells of the rabbit superior mesenteric artery in Krebs solution, i.e. ACh hyperpolarizes the membrane, while it consistently generates contraction. These ACh actions on the muscle cells were modified by aging.
ANTAGONISTIC EFFECT OF COMPOUND 48/80 ON THE INHIBITORY ACTIONS OF MORPHINE AND METHIONINE‐ENKEPHALIN ON ELECTRICALLY‐INDUCED CONTRACTIONS OF THE GUINEA‐PIG ILEUM
Authors: KAMIKAWA YUICHIRO , SHIMO YASUO 
Published: July 2012

The effect of compound 48/80 was studied on the twitch‐like contractions of the longitudinal muscle of guinea‐pig ileum induced by electrical stimulation of intramural cholinergic nerves.
Compound 48/80 alone, at concentrations up to 30 μg/ml, had no effect on the twitch contractions. The contraction to exogenously applied acetylcholine was slightly depressed by the compound.
At 100 μg/ml, compound 48/80 caused a weak but long‐lasting increase in tone and irregular contractile activity in the ileum, part of which was reduced but not completely abolished by pretreatment with chlorpheniramine (1 μm) or by repeated applications of compound 48/80.
The inhibitory effects of morphine and methionine‐enkephalin on the twitches were antagonized by the presence of compound 48/80 (3 to 30 μg/ml), possibly in a competitive manner. The antagonism was not affected by pretreatment with the antihistaminics, chlorpheniramine and/or metiamide.
The inhibitory effects of noradrenaline and adrenaline on the twitches were slightly but significantly increased by the presence of compound 48/80 (10 or 30 μg/ml), whereas that of ATP was not modified.
These results indicate that compound 48/80 acts as a selective and competitive antagonist at opiate receptors located in the intramural cholinergic nerves of guinea‐pig ileum.
MECHANISMS OF INACTIVATION OF NORADRENALINE IN THE IRIS SPHINCTER, TRACHEAL MUSCLE AND FACIAL ARTERY OF CATTLE: IMPLICATIONS FOR β‐ADRENOCEPTOR‐MEDIATED RESPONSES
Authors: KALSNER STANLEY 
Published: July 2012

The rôle of neuronal and extraneuronal pathways of amine inactivation in regulating the inhibitory actions of noradrenaline was investigated in three bovine smooth muscle preparations in which the primary adrenoceptor is of the j?‐type.
The extraneuronal uptake inhibitor, 17β‐oestradiol, sensitized the inhibitory responses to noradrenaline in the facial artery, the iris sphincter and in tracheal muscle preparations, indicating a major rôle for non‐neuronal processes in agonist‐inactivation in all three preparations. Cocaine also increased responses to noradrenaline, pointing to a rôle for neuronal uptake either as a terminating mechanism or as a process limiting access of exogenous agonist molecules to their site of action.
Cocaine did not enhance significantly responses to isoprenaline, a potent β‐adrenoceptor agonist which is not taken up neuronally. Further, relaxations to metaraminol, a sympathomimetic amine which is taken up extraneuronally, but much less so than noradrenaline, were also less enhanced by 17β‐oestradiol in the three preparations tested. These findings support the specificity of action of cocaine and 17β‐oestradiol as neuronal and extraneuronal uptake inhibitors in the present experiments.
Studies of the uptake of [3H]‐noradrenaline revealed that 17β‐oestradiol reduced the uptake of amine in the presence of cocaine, confirming a cocaine‐resistant site of action for the steroid in all three preparations.
It is concluded that extraneuronal uptake sites are located sufficiently close to the β‐adrenoceptors to modulate the concentration and duration of action of noradrenaline at these sites of action. It is proposed that in smooth muscles which contain a preponderance of β‐receptors, extraneuronal metabolism is a key event in terminating the inhibitory effects produced.
SYMPATHOMIMETIC EFFECTS OF PANCURONIUM BROMIDE ON THE CARDIOVASCULAR SYSTEM OF THE PITHED RAT: A COMPARISON WITH THE EFFECTS OF DRUGS BLOCKING THE NEURONAL UPTAKE OF NORADRENALINE
Authors: DOCHERTY J.R. , McGRATH J.C. 
Published: July 2012

The effects of pancuronium bromide on the cardiovascular system of the pithed rat were examined. Pancuronium had two effects, a short‐lasting cardiovascular stimulation following injection and a longer‐lasting potentiation of responses to sympathetic nerve stimulation.
The initial effect of pancuronium was compared with that of tyramine. The cardioaccelerator but not the pressor responses to both pancuronium and tyramine were significantly reduced following sympathectomy with 6‐hydroxydopamine (6‐OHDA).
The action of pancuronium in potentiating sympathetic nerve responses was compared with that of known blockers of the neuronal uptake of noradrenaline (NA). Pancuronium (1 mg/kg) and cocaine (0.5 mg/kg) potentiated cardioaccelerator and pressor responses to sympathetic stimulation. These effects of pancuronium could be obtained following adrenalectomy and during neuromuscular blockade with gallamine. Pancuronium and uptake blockers potentiated the cardioaccelerator response to NA, reduced the response to tyramine, but did not affect the response to isoprenaline. Pancuronium and uptake blockers potentiated the pressor response to NA, but did not affect the response to tyramine or clonidine.
Following sympathectomy with 6‐OHDA, pancuronium failed to potentiate cardioaccelerator and pressor responses to NA.
These results are discussed in relation to two main cardiovascular effects of pancuronium; an indirect sympathomimetic action and blockade of the neuronal uptake of NA.