bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Withdrawal from Chronic Ethanol Ingestion on the cAMP Response of Cerebral Cortical Slices Using the Agonists Histamine, Serotonin, and Other Neurotransmitters
Authors: French Samuel W. , Palmer Douglas S. , Narod Mary E.
Published: April 2011

The effect of ethanol withdrawal on the cAMP response of cerebral cortical brain slices was studied. The cAMP response was evoked in vitro by various neurotransmitters including norepinephrine (NE), histamine, serotonin, dopamine, acetylcholine, and γ-aminobutyric acid (GABA). The cAMP response to NE and histamine was enhanced by ethanol withdrawal. Serotonin evoked a cAMP response in the brain slices from ethanol-withdrawal rats but not in pair-fed controls. The histamine and serotonin evoked responses were blocked by chlortripolon and methysergide, respectively. The responses to histamine and serotonin were also blocked by a- and β-adrenergic antagonists, possibly because of the nonspecific membrane stabilizing effect of these antagonists. GABA inhibited the NE stimulated cAMP response possibly through the hyperpolarizing action of GABA. The results support the hypothesis that ethanol withdrawal induces a nonspecific postjunctional supersensitivity. It is postulated that the supersensitivity involves a partial depolarization of the receptor membrane. Alternative hypotheses are reviewed.
Effect of a Chronic Suboptimal Intake of Magnesium on Magnesium and Calcium Content of Bone and on Bone Strength of the Rat
Authors: Héroux O. , Peter D. , Tanner A.
Published: April 2011

Sprague–Dawley rats were kept at 28 °C from 21 to 517 days age and fed one of the two following diets: a semi-purified diet containing 502 p.p.m. of Mg (control) or the same diet containing only 120 p.p.m. (mg/kg) (low-Mg). The chronic suboptimal intake of Mg by rats fed the low-Mg diet did not result in overt signs of Mg deficiency even when Mg levels were greatly reduced in carcass, plasma, and tibia, but it significantly decreased bone strength. It is suggested that Mg deficiency in man could be a factor in the weakening of bone, commonly observed in old age, even when there are no visible signs of Mg deficiency. Studies of the human situation would be of interest.
Propranolol antagonism to the effect of furosemide on the composition of endolymph in guinea pigs
Authors: Brusilow Saul W.
Published: April 2011

Furosemide, administered intravenously (50 mg/kg) to guinea pigs, caused an increase in the sodium concentration and a decrease in the potassium concentration of endolymph, and a fall in the endolymphatic potential. The furosemide-induced electrolyte changes were prevented by pretreatment of five guinea pigs with propranolol given intravenously (2 mg/kg). The fall in the endolymphatic potential was not prevented by propranolol. Local administration of furosemide to the perilymphatic or endolymphatic space caused a fall in the endolymphatic potential, but had no effect upon the concentrations of sodium and potassium of endolymph. These studies provide additional information suggesting the mutual independence of the endolymphatic potential and sodium and potassium concentration gradients.
Descending influences of periaqueductal gray matter and somatosensory cerebral cortex on neurones in trigeminal brain stem nuclei
Authors: Sessle B. J. , Dubner R. , Greenwood L. F. , Lucier G. E.
Published: April 2011

Single relay (to thalamus) and nonrelay neurones that responded to innocuous and/or noxious oral–facial stimuli were located in trigeminal brain stem nuclei oralis and caudalis. The responses of the cells and the digastric muscle to these stimuli were tested with conditioning stimulation of the periaqueductal gray matter (PGM) and somatosensory cerebral cortex in cats. A greater suppression of nociceptive responses with PGM stimulation was noted, and this effect may contribute to the profound analgesic action that has been reported to occur with PGM stimulation.
Longitudinal extension of the pulmonary trunk during breathing in young rabbits: a possible factor in elastin fragmentation
Authors: Smith Paul H.
Published: April 2011

Corrosion casts of the pulmonary trunk and major branches of the pulmonary arteries of 39 rabbits were made from a silicone polymer. In half of the rabbits the casts were made with the lungs expanded and half with the lungs collapsed. The length of various segments of the casts were measured from magnified photographs. It was found that in rabbits less than 23 days old the pulmonary trunk is significantly longer when the lungs are expanded than when they are collapsed. This suggests that a repeated longitudinal extension of the vessel occurs during breathing. This effect disappears after 30 days of age, possibly because of elastin fragmentation. Between the ages of 23 and 30 days the growth in length and diameter of the pulmonary trunk undergoes a rapid acceleration. This may also be the result of elastin fragmentation. Whereas it may be that repeated longitudinal stress in the pulmonary trunk during breathing causes elastin in its media to fragment, one cannot exclude the possibility that other factors such as growth are responsible.
Propranolol induces acute natriuresis by β blockade and dopaminergic stimulation
Authors: Carrara M. C. , Baines A. D.
Published: April 2011

dl-Propranolol (0.8–1.6 mg/kg∙h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin–angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by β blockade and requires postganglionic nerve function but is independent of α receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal β blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking β receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.
Regulation of glucagon-stimulated production of glucose in rat liver by guanosine 3′,5′-cyclic phosphate
Authors: Epand Richard M. , Prosser Connie
Published: April 2011

Exogenous cGMP can inhibit both basal and glucagon-stimulated production of glucose in liver slices from fed rats. Thus, cAMP and cGMP have opposite effects on the production of glucose in rat liver. Acetylcholine, an activator of guanylate cyclase (EC 4.6.1.2) in other systems, also inhibits the glucagon-stimulated production of glucose. No effect on glucose production was observed with secretin or exogenous GTP.
NADPH-dependent lipid peroxidation and its effects on aminopyrine N-demethylation in subcellular fractions of human neonatal liver
Authors: Renton Kenneth W. , Aranda Jacob V. , Eade Norman R.
Published: April 2011

NADPH-dependent lipid peroxidation was determined in humans, using subcellular fractions of livers obtained from newborn infants. As reported for other species, activity was concentrated in the microsomal fraction and was similar to that found in the rat. High activity of lipid peroxidation induced by iron decreased aminopyrine N-demethylation and slightly reduced linearity time for the reaction. Compared with the rat, however, human microsomes were more resistant to the effects of lipid peroxidation. If lipid peroxidation occurs in vivo it is unlikely to affect drug oxidation to any great degree in human infants.
The necessity of drug level monitoring in anticonvulsant drug therapy
Authors: Davis H. Lorne , Bailey David G. , Johnson Gordon E. , Wilson Thomas W.
Published: April 2011

A survey of 'steady-state' serum levels of anticonvulsant drugs from 221 epileptic patients at a university hospital was conducted. Serum concentrations of phenobarbital, primidone, and diphenylhydantoin were determined by a gas chromatographic method. Sixty-five percent (130) of the patients receiving diphenylhydantoin had levels below the therapeutic range of 10–20 μg/ml. Subtherapeutic levels appear to be due to inadequate dosage adjustment. Only 25% (33) of the patients receiving phenobarbital had levels below the therapeutic range. Serum levels of diphenylhydantoin or phenobarbital could not be predicted from dosage. Most patients received two or more drugs. Over 10% of the patients had potentially toxic levels of anticonvulsant drugs. High levels of diphenylhydantoin were easily recognized clinically but high levels of phenobarbital were not.
Enhancement (by ATP, insulin, and lack of divalent cations) of ouabain inhibition of cation transport and ouabain binding in frog skeletal muscle; effect of insulin and ouabain on sarcolemmal (Na + K)MgATPase
Authors: Manery J. F. , Dryden E. E. , Still J. S. , Madapallimattam G.
Published: April 2011

Using small, intact frog muscles, the basic properties of Na+ and K+ transport were shown to resemble those of the (Na+ + K+) Mg2+ATPase (EC 3.6.1.3) isolated from skeletal muscle, (a) External K+ is essential for Na+ exit and K+ entry after the muscles are Na+-loaded and K+-depleted; (b) the ouabain concentration causing maximum inhibition of recovery is the same for transport as for the inhibition of the isolated enzyme. Ouabain causes a decrease in the sorbitol space and causes muscle fibre swelling. Absence of Ca2+ and Mg2+ inhibits recovery of normal Na+ and K+ concentrations and increases the sorbitol space. Insulin stimulates K+ uptake and Na+ loss in intact muscles but has no effect on the isolated sarcolemmal (Na+ + K+) Mg2+ATPase. Absence of divalent cations, addition of external ATP and of insulin enhance the ouabain inhibition of recovery.Bound ouabain was measured using [3H]ouabain and [14C]sorbitol (to measure the extracellular space). The process of binding was slowly reversible and was saturable within a range of ouabain concentrations from 1.48 × 10−7 to 5.96 × 10−7 M. From the nonexchangeable ouabain bound, the density of glycoside receptors was estimated to be 650 molecules per square micrometre of membrane surface. The absence of divalent cations, addition of external ATP and of insulin significantly enhanced the amount of ouabain bound. Substitution of Na+ and K+ by choline greatly reduced the bound ouabain.
Nonshivering thermogenesis in the rat. I. The relation between drug-induced changes in thermogenesis and changes in the concentration of plasma cyclic AMP
Authors: Foster David O. , Frydman M. Lorraine , Usher Jeffrey R.
Published: April 2011

Barbital-sedated, cold-acclimated (CA) or warm-acclimated (WA) rats were given different doses and combinations of noradrenaline, theophylline, and the adrenergic-blocking agents propranolol and phentolamine, to stimulate or inhibit calorigenesis in various ways. To see whether the effects of these drugs on calorigenesis could be ascribed to effects on the adenylate cyclase (EC 4.6.1.1) – cyclic AMP system, and to try to assess thereby the significance of this system in the regulation of nonshivering thermogenesis (NST), changes in the concentration of plasma cyclic AMP were measured as an index (Broadus, A.E., Hardman, J. G., Kaminsky, N. I., Ball, J. H., Sutherland, E. W., and Liddle, G. W.: 1971. Ann. N.Y. Acad. Sci. 185, 50–60) of changes in tissue levels of cyclic AMP. In CA rats, which have a severalfold greater capacity for NST than WA rats, calorigenic responses to noradrenaline, theophylline, noradrenaline plus theophylline, or phentolamine plus theophylline were as much as four times larger than in WA rats. However, the changes in level of plasma cyclic AMP produced by each of these and other treatments were virtually the same for both groups. It would appear, therefore, that the difference between WA and CA rats in ability to produce heat by NST is not a function of the amplitude of changes in tissue levels of cyclic AMP. Nevertheless, it was also observed, and was particularly striking in CA rats, that when a drug or combination of drugs had a stimulatory, inhibitory, or synergistic effect on calorigenesis, it had a similar effect with respect to elevation of plasma cyclic AMP. Altogether, the results indicate that adenylate cyclase and cyclic AMP are likely to be participants in the regulation of NST in the rat, but that they would be subservient in this regard to whatever factors are responsible for acclimation-related differences in capacity for NST.
Further identification of multiple responses mediated by dopamine in the CNS of Planorbis corneus
Authors: MacDonald J. F. , Berry M. S.
Published: April 2011

Intracellular recordings from neurones, receiving monosynaptic contacts from a dopamine-containing (DA-containing) neurone in the central ganglia of the gastropod mollusc Planorbis corneus, revealed that there are at least three DA-mediated responses. These are 'fast' excitatory postsynaptic potentials (EfPSPs) (200 ms), 'slow' excitatory postsynaptic potentials (EsPSPs) (900 ms), and inhibitory postsynaptic potentials (IPSPs) (200–900 ms). Various combinations of these synaptic potentials were recorded from postsynaptic neurones: EsPSPs, EfPEPs, EsEfPSPs, or EfIPSPs. Neurones receiving such connections also responded appropriately to iontophoresized DA with a 'fast' depolarization (EfPSPs), a 'slow' depolarization (EsPSPs), or a hyperpolarization (IPSPs). These responses could be distinguished on the basis of function (excitation or inhibition), duration, rate of desensitization, and sensitivity to apomorphine, D-LSD, and tubocurarine. The neuroleptic drugs (DA antagonists) haloperidol, fluphenazine, and metoclopramide reduced both excitatory and inhibitory DA transmission. This investigation strongly supports the hypothesis that DA is the transmitter mediating multiple synaptic responses in Planorbis.
Effect of L-cycloserine on brain GABA metabolism
Authors: Wood J. D. , Peesker S. J. , Gorecki D. K. J. , Tsui D.
Published: April 2011

The administration of L-cycloserine to mice resulted in a dramatic decrease in the activities of 4-aminobutyrate:2-oxoglutarate aminotransferase (GABA-T) and L-alanine:2-oxoglutarate aminotransferase (ALA-T) in both brain and liver, L-Aspartate:2-oxoglutarate aminotransferase was inhibited only slightly, and brain glutamic acid decarboxylase not at all. Liver ALA-T activity returned to near normal levels within 24 h of L-cycloserine administration whereas liver GABA-T and brain ALA-T activities had returned only halfway to normal levels in the same time period. The recovery in the activity of brain GABA-T was even slower. A consequence of the inhibition of brain GABA-T activity was an elevation in the GABA content of the tissue which was maximal 3 h after L-cycloserine administration and which was still noticeable 8 h after the drug treatment. L-cycloserine was also a potent in vitro inhibitor of brain GABA-T activity. The inhibition was competitive with respect to GABA, the Ki value being 3.1 × 10−5 M. The prior administration of L-cycloserine to mice significantly delayed the onset of isonicotinic acid hydrazide induced convulsions.
Reversal of myocardial dysfunction in endotoxin shock with insulin
Authors: Archer L. T. , Beller B. K. , Drake J. K. , Whitsett T. L. , Hinshaw L. B.
Published: April 2011

Recent data reported from this laboratory have documented myocardial functional depression in endotoxin shock. The purpose of the present study was to determine the effects of insulin on the dysfunctioning canine myocardium subjected to lethal endotoxin shock. Experiments were conducted on isolated working left ventricular preparations in which LD90–100 endotoxin was administered prior to, or following, isolation of the heart. Determinations of myocardial performance were conducted under the conditions of controlled mean aortic pressure and cardiac output. Myocardial dysfunction occurred between 2 and 6 h postendotoxin, as evidenced by significantly increased left ventricular end-diastolic pressure, decreased power, and depressed negative dP/dt, although blood glucose concentrations were maintained at control values. Intraatrial infusions of insulin at rates of 6 U/min reversed all signs of myocardial dysfunction. During insulin infusion, heart rates decreased (p < 0.02) and myocardial lactate uptake increased (p < 0.02), while oxygen uptake and coronary blood flow were insignificantly altered.
Circulating natriuretic and kaliuretic factors in acute uremia: The role of the kidney
Authors: Wilson Douglas R. , Honrath Ursula
Published: April 2011

The role of the kidney as a source or as the excretory route for natriuretic and kaliuretic factors present in acute uremia was studied using the technique of isovolemic cross-circulation in 49 pairs (eight groups) of anaesthetized rats. Marked and similar natriuresis, kaliuresis, and diuresis occurred in recipients undergoing cross-circulation with donors subjected to either bilateral nephrectomy or total intravenous urine reinfusion for 18 h previously, and were not seen with sham-operated donors. Similar and significant, but less marked, changes occurred in two groups with bilateral nephrectomy or urine reinfusion of only 3 h duration. Urea-loaded normal donors caused a natriuresis and kaliuresis which was similar to the two 18-h uremic donor groups. When donor animals were sodium depleted prior to bilateral nephrectomy, the natriuretic response in the recipients was significantly reduced. The results indicate that the kidney is not necessary for the rapid appearance of natriuretic and kaliuretic activity in the blood of acutely uremic animals, and that such activity results from the retention of factors of extrarenal origin. Natriuresis and kaliuresis result from inhibition of tubular reabsorption and are not dependent on changes in glomerular filtration or renal hemodynamics, Pitressin or aldosterone levels. Urea appears to be a major component of the circulating natriuretic and kaliuretic activity in acute uremia but evidence of other factors was also obtained.
Development of cardiovascular responses to noradrenaline, adrenaline, normetanepnrine, and metanephrine in the unanesthetized fetus
Authors: Harris W. H. , Petten G. R. Van
Published: April 2011

The cardiovascular responses to the catecholamines noradrenaline (NA) and adrenaline (A) and their metabolites normetanephrine (NM) and metanephrine (M) were determined in the chronically prepared ovine fetus (112–145 days), newborn lamb (6–12 or 96 h), and adult sheep to assess the development of responsiveness to these biogenic amines. With NA, NM, and M there was a gradual significant increase in the pressor response with advancing gestation and a larger increase between late term and the newborn period where the response was still only about one-half of the adult. With A, there was only a significant increase in pressor response after birth to a level about one-half the adult response. In all age groups the pressor response to these amines was accompanied by bradycardia which was especially marked with A; pretreatment with atropine blocked the reflex bradycardia and resulted in an increase in the magnitude of the pressor response. The duration of the NA pressor response decreased only slightly in the near-term fetus but decreased markedly in the newborn lamb to a value similar to the adult. There were no differences in any age groups in the ratios of the responses to NA and A and their respective metabolites. These data indicate gradual development of the responsiveness of the ovine cardiovascular system to endogenous pressor amines over the last third of gestation with a further increase immediately after birth to a level still below the adult, early development of alpha receptors capable of discriminating neurohormones from metabolites and rapid development at or near term of mechanisms involved in terminating the action of NA.
Altered effect of insulin and catecholamines in brown adipose tissue of cold-acclimated rats
Authors: Bégin-Heick Nicole , Noland Iris , Dalpé Marthe , Heick H. M. C.
Published: April 2011

Data are presented indicating that in brown adipose tissue (BAT) of cold-acclimated (CA), but not cold-exposed (CE) rats, there was an alteration in the relative response to catecholamines and insulin as evidenced by increased binding of alprenolol and decreased binding of insulin to plasma membrane enriched fractions. In addition, the stimulatory effect of insulin on glucose incorporation into glycogen and its inhibitory action on adenylate cyclase activity were both blunted in the CA tissues. It is proposed that shifts in the capacity of BAT to respond to catecholamines and insulin may be involved in the mechanism of cold acclimation.
Serum MSH levels and pituitary MSH contents: Their fluctuation during pregnancy in the rat
Authors: Volosin Marta , Celis M. E.
Published: April 2011

MSH was measured by a biological assay in the pituitary and serum of the rat during the whole term of pregnancy. The peptide showed changes in early pregnancy in serum, during the middle of pregnancy values of serum MSH became negative, and in late pregnancy it was possible to find high values during days 18 and 19 before delivery. Comparison between the amount of pituitary MSH and that in serum seems to show that between days 10 and 15 there is practically no, or just a little, MSH synthesis, since the MSH values in serum are negative although the content of pituitary MSH is also low. A relation between the results found by other authors and that found by us was analyzed.
Electrical coupling in rat myometrium during pregnancy
Authors: Zelcer Elane , Daniel E. E.
Published: April 2011

Gap junctions were found in rat myometrium only during parturition or abortion. A comparison was made between the values of the length constants obtained from longitudinally cut strips of rat myometrium at the midterm stage of pregnancy and during parturition. No significant difference was found between these values. No significant difference was found between length constants measured in myometrium from rats near term (22 days) and those during parturition, or between midterm myometrium and myometrium taken from animals aborting at midterm following ovariectomy. It was concluded that the appearance of gap junctions in parturient myometrium does not alter the spread of passive current in the longitudinal axis of the cells in these tissues. It is suggested that gap junctions are not required for spread of passive current, and that other structures may provide an alternate path.
Apparent volume of the biliary tree in the dog
Authors: Barnhart James L. , Combes Burton
Published: April 2011

The apparent volume of the biliary tree (ABV) in the dog was determined by measuring the mean biliary transit time of injected [14C]taurocholate ([14C]TC). After bolus injection of [14C]TC, entry of bile salt into the lumen of the biliary tree is signaled by an increase in bile flow. The volume of bile collected at the common duct from onset of choleresis until maximal concentration of 14C radioactivity is reached in bile minus the calculated quantity of bile that contains radioactivity and the cannula volume yields a value for the volume of the biliary tree present just prior to injection of [14C]TC. The mean value for ABV in 19 dogs was 2.49 ± 0.65 μL/g liver (mean ± SD).
Calcium binding in cardiac sarcolemma
Authors: Morcos N. C. , Jacobson A. L.
Published: April 2011

The relationship between calcium binding and ATPase activity has been investigated for guinea pig cardiac sarcolemma. The concentrations of calcium ions and of ATP were the main factors in determining the amount of calcium bound. With a saturating concentration of ATP, at low calcium concentrations (0.1 mM) more than 50% of the total calcium bound was ATP dependent while at high concentrations of calcium (10 mM) only 20% of the calcium bound was ATP dependent. The ATP-dependent calcium binding process involves one class of calcium binding sites while the non-ATP-dependent calcium binding process involves two classes of binding sites.Inhibitor studies of Ca2+-stimulated MgATPase, MgATPase, and CaATPase activities suggest Ca2+ and Mg2+ are either interacting with different sites on the same enzyme or with different enzymes.
Effect of isoproterenol on phosphorylase activation in the hyperthyroid rat heart
Authors: Longhurst Penelope A. , McNeill John H.
Published: April 2011

Pretreatment of rats for 3 days with triiodothyronine produced an increase in rate in the right atrium and a decrease in force of contraction in the right ventricle and Langendorff heart.Isoproterenol administration produced a time-dependent increase in rate and tension. The increase in rate was consistently greater in atria from hyperthyroid rats, and the increase in tension consistently greater in tissues from euthyroid rats. Isoproterenol also produced a time- and dose-dependent increase in phosphorylase a activity. In the isolated atria and ventricles enzyme activity was similar in the two groups. In the Langendorff hearts, however, there was an enhancement of the isoproterenol-induced increase in phosphorylase activity in hearts from hyperthyroid rats. Reduction of the coronary blood flow to the level found in euthyroid animals did not reduce the potentiation of phosphorylase activation found in hearts from hyperthyroid rats.It is concluded that the potentiation of phosphorylase activation in hearts from hyperthyroid rats is not due to the increase in coronary blood flow.
Patterns of early and late discharges in somatotopically identified precentral neurons in awake monkeys in response to somatic inputs
Authors: Wong Y. C. , Kwan H. C. , Murphy J. T.
Published: April 2011

Extracellular recordings were made of single neurons in precentral cortex of awake monkeys. These neurons were somatotopically identified with respect to their responses to inputs from single joints or their somatic surround. Many of these neurons exhibited early (< 50 ms) and late (> 50 ms) discharges in response to flexion or extension torques delivered about the wrist. With the monkey in a mode requiring opposition to the injected torque, all responsive neurons showed a parallel excitatory or inhibitory modification in the early and late discharges. This was true both for cells identified as wrist (flexion–extension) neurons and those identified as nonwrist (flexion–extension) neurons. These findings indicate that the reflex and voluntary components of precentral discharge invariably show a congruent functional response to a torque disturbance, for this particular instruction set.
The effects of cold-induced muscle spindle secondary activity on monosynaptic and stretch reflexes in the decerebrate cat
Authors: Chapman C. E. , Michalski W. J. , Séguin J. J.
Published: April 2011

The effects of muscle spindle secondary ending activity on the stretch reflex were studied in unanesthetized decerebrate cats. Activation of secondary endings was accomplished by reducing the muscle temperature. This has been shown to cause a sustained asynchronous discharge from secondary endings. Cooling of the medial gastrocnemius or lateral gastrocnemius–soleus muscles caused an increase in the phasic and tonic components of their stretch reflexes. Cooling of the relaxed medial gastrocnemius muscle caused similar increases in the components of the stretch reflex of the synergistic lateral gastrocnemius–soleus muscle and an increase in its monosynaptic reflex. It was concluded that the facilitatory autogenetic and synergistic effects of muscle cooling on the stretch and monosynaptic reflexes were brought about by activity in group II afferents from muscle spindle secondary endings and could not be ascribed to any other type of muscle receptor. These results support the concept of an excitatory role for the secondary endings of the muscle spindle in the stretch reflex of the decerebrate cat.
Effect of adrenalectomy on convulsions induced by high-pressure oxygen
Authors: Singh A. K. , Banister E. W.
Published: April 2011

Adrenalectomized rats exposed to high pressure oxygen (OHP) until convulsion convulse much later than sham-operated or normal rats. No significant changes in the concentration of noradrenaline (NA) and total catecholamines (TC) in the brain were noted in sham-operated or adrenalectomized rats resulting from sham or real surgery and no change occurred in these variables in normal sham-operated or adrenalectomized animals after OHP leading to convulsion. Brain adrenaline (A) concentration, however, decreased significantly in all three groups following OHP-induced convulsions. Activity of catecholamine O-methyltransferase (COMT) decreased significantly only in adrenalectomized rats. Brain γ-aminobutyric acid (GABA), glutamate, and other amino acid level remained unchanged after adrenalectomy whereas the concentration of ammonia decreased significantly when normal rats were adrenalectomized. After OHP-induced convulsions, the concentrations of brain GABA and glutamate decreased and ammonia and glutamine plus asparagine increased significantly in normal, sham-operated, and adrenalectomized rats. In the blood no significant difference was noted in the concentration of the catecholamines, ammonia, and amino acids either in normal or sham-operated rats. In adrenalectomized rats, the blood A and NA concentrations decreased significantly and tyrosine increased significantly. The concentration of NA, ammonia, and glutamine plus asparagine in rats from all three groups increased after OHP-induced convulsions, whereas the concentration of glutamate decreased significantly. Since the concentration of A increased significantly after convulsions in normal and sham-operated rats but did not change in adrenalectomized rats, it might be proposed that adrenalectomy protects against OHP-induced convulsions by reducing the circulating concentration of A and ammonia.However, these are not the only factors involved in the protection since the sham-operated rats also convulsed much later than normal rats but had similar ammonia and A concentrations to normal animals.
Effects of noradrenaline and nicotinic acid on plasma free fatty acids and oxygen consumption in cold-adapted rats
Authors: Lafrance Louise , Routhier Danièle , Têtu Bernard , Têtu Christian
Published: April 2011

A 3-h noradrenaline (NA) infusion (1.5 μg kg−1 min−1) produced a sustained enhanced oxygen consumption (O2 cons.) in cold-adapted rats. Plama free fatty acid (FFA) levels were elevated by NA in control and in cold-adapted rats, but to a lesser extent in cold-adapted rats; the increase was maintained at a plateau in both groups during the entire period of NA infusion. A 1-h nicotinic acid (Nic A) infusion (1.5 mg kg−1 min−1) added to the NA infusion inhibited the calorigenic response to NA in cold-adapted rats and reduced the elevated plasma FFA concentration in control and in cold-adapted rats to values below basal levels. However, when the Nic A infusion was stopped, the O2 cons, was increased again in cold-adapted rats by the uninterrupted NA infusion, without the simultaneous increase of the plasma FFA concentration; the plasma FFA concentration was maintained in cold-adapted rats below basal values and merely brought back to basal levels in control rats. From these results, it is suggested that plasma FFA are not an essential substrate to the calorigenic response to NA observed in cold-adapted rats, as 85% of the response can occur when the plasma FFA concentration is very low.
Isoniazid phenotyping of black as well as white patients
Authors: Hodgkin M. M. , Eidus L. , Bailey W. C.
Published: April 2011

The isoniazid phenotyping in black patients from Birmingham (Alabama) as well as from South Africa yielded a higher frequency of fast inactivation than that in the Canadian and U.S. white participants. Following an oral test dose of 10 mg isoniazid per kilogram, the incidence of fast acetylation was 58.7 and 60.3% in South African and Birmingham blacks, respectively. In the Canadian and Birmingham Caucasians the rate was 41.9 and 41.0%, respectively.
Calcium antagonists and contractile responses in rat vas deferens and guinea pig ileal smooth muscle
Authors: Triggle C. R. , Swamy V. C. , Triggle D. J.
Published: April 2011

The effect of depletion of extracellular Ca2+ (Ca2+ext) on the loss of responsiveness of the guinea pig ileal longitudinal muscle (g.p.i.l.m.) and the rat vas deferens (r.v.d.) to K+ and cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD), and K+ and noradrenaline (NA), has been examined and compared with the effects of a variety of local anesthetics and calcium antagonists. The results indicate that qualitative similarities are apparent with respect to the dependence of agonist-induced activity on Ca2+ext in both the g.p.i.l.m. and r.v.d. Distinct differences, however, in the Ca2+ translocation processes in these two tissues, in response to the different agonists, can be shown by the use of a variety of 'calcium antagonists' thus indicating that such translocation processes are both tissue and agonist selective.It is thus noted that, contrary to the Ca2+ depletion studies, D 600 and the usually more potent BAY-1040 showed no discrimination of action or potency in their ability to inhibit components of the NA response in the r.v.d. In contrast, D 600 and the more potent BAY-1040 selectively inhibited the tonic component of the K+ response. Treatment with SKF 525A and parethoxycaine (PC) in the g.p.i.l.m. and SKF 525A in the r.v.d. resulted in a nonselective inhibition of responses of the tissues to all stimulants. However, in the r.v.d. PC potentiated NA action, and its methobromide (MeBr) derivative potentiated both NA and K+ action and also, like PC, partially shifted to the left the dose-response curve to Ca2+ in NA-depolarizing Ca-free Tyrode's. The quaternary MeBr and the tertiary 2-chloroethyl (2Cl) derivatives of SKF 525A and PC were selectively more effective against CD- than K+-supported contractile activity in the g.p.i.l.m. and the 2Cl derivatives were more effective against NA than K+ responses in the r.v.d. The 2Cl derivative of PC also was more effective in antagonizing the Ca2+ dose–response curve in high-CD or high-NA than in high-K+ Ca2+-free Tyrode's.
Changes in core temperature and feeding in rats by levorphanol and dextrorphan
Authors: Thornhill J. A. , Hirst M. , Gowdey C. W.
Published: April 2011

Male Sprague–Dawley rats received saline for 5 days before and 5 days after daily subcutaneous injections of levorphanol or dextrorphan tartrate (8 mg base/kg) for 10 days. Core temperatures, measured by telemetry, and acquisition of food pellets on a continuous reinforcement schedule were monitored simultaneously and recorded every 30 min for each rat throughout the experiment. After the first levorphanol injections signs of acute intoxication were apparent, and a mild but delayed hyperthermia was observed and food intake declined. With repeated injections of levorphanol peak hyperthermia increased and occurred with a shorter latency after administration, as did a phase of 'stimulated' feeding activity. This phase of vigorous feeding during light hours markedly disrupted the characteristic diurnal pattern of daily food intake. During withdrawal temperatures decreased, feeding became more intermittent, and signs of increased irritability were evident in the levorphanol group. Patterns during daily injections of dextrorphan, and after its withdrawal, were similar to those in the saline control period. These results indicate that the patterns of change in temperature and feeding responses to levorphanol are similar to those found earlier with heroin, codeine, and morphine, and that these changes involve stereospecific receptors.
Behavioural effects of 6-hydroxydopamine-induced depletion of spinal noradrenaline
Authors: Roberts D. C. S. , McCaughran Jr. J. A. , Fibiger H. C.
Published: April 2011

Bilateral injection of 6-hydroxydopamine (4 μg/2 μL) into the caudal medulla of rats reduced spinal noradrenaline (NA) to 6% of control values. No significant NA depletion was observed in the hippocampus, cortex, or cerebellum, and a small loss of NA was found in the hypothalamus. These lesions were found to elevate significantly threshold shock levels necessary to elicit jump responses, and they also abolished the reflexive alternating motor movements produced by decapitation. These data support the hypothesis that spinal NA mechanisms modulate reflexive motor movements. However, no significant effect of these lesions was found on either spontaneous or amphetamine-induced locomotor activity, suggesting that spinal NA does not play a significant role in these behaviours.
Continuation of fast axonal transport in regenerating axons in vitro
Authors: Bisby M. A. , Hilton C. E.
Published: April 2011

A previous study by McLean and co-workers reported that regenerating axons of the rabbit vagus nerve were unable to sustain axonal transport in vitro for several months after nerve injury. In contrast, we found that sensory axons of the rat sciatic nerve were able to transport 3H-labeled protein into their regenerating portions distal to the site of injury within a week after injury when placed in vitro. Transport in vitro was not significantly less than transport in axons maintained in vivo for the same period. Transport occurred in the medium that was used by the McLean group, but was significantly reduced in calcium-free medium. When axon regeneration was delared, only small amounts of activity were present in the nerve distal to the site of injury, showing that labeled protein normally present in that part of the nerve was associated with axons and was not a result of local precursor uptake by nonneural elements in the sciatic nerve. We were not able to explain the failure of McLean and co-workers to demonstrate transport in vitro in regenerating vagus nerve, but we conclude that there is no general peculiarity of growing axons that makes them unable to sustain transport in vitro.
Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex
Authors: Phillis J. W. , Edstrom J. P. , Kostopoulos G. K. , Kirkpatrick J. R.
Published: April 2011

Adenosine and the adenine nucleotides have a potent depressant action on cerebral cortical neurons, including identified corticospinal cells. Other purine and pyrrolidine nucleotides were either weakly depressant (inosine and guanosine derivatives) or largely inactive (xanthine, cytidine, thymidine, uridine derivatives). The 5′-triphosphates and to a lesser extent the 5′-diphosphates of all the purine and pyrimidines tested had excitant actions on cortical neurons. Adenosine transport blockers and deaminase inhibitors depressed the firing of cortical neurons and potentiated the depressant actions of adenosine and the adenine nucleotides. Methyl-xanthines (theophylline, caffeine, and isobutylmethylxanthine) antagonized the depressant effects of adenosine and the adenine nucleotides and enhanced the spontaneous firing rate of cerebral cortical neurons. Intracellular recordings showed that adenosine 5′-monophosphate hyperpolarizes cerebral cortical neurons and suppresses spontaneous and evoked excitatory postsynaptic potentials in the absence of any pronounced alterations in membrane resistance or of the threshold for action potential generation. It is suggested that adenosine depresses spontaneous and evoked activity by inhibiting the release of transmitter from presynaptic nerve terminals. Furthermore, the depressant effects of potentiators and excitant effects of antagonists of adenosine on neuronal firing are consistent with the hypothesis that cortical neurons are subject to control by endogenously released purines.
The mineralocorticoid activity of 18-hydroxy-11-deoxycorticosterone, 11-deoxycorticosterone, and aldosterone in the adrenalectomized dog
Authors: Constantopoulos George , Kusumoto Miyako , Gutkowska Jolanta , Genest Jacques
Published: April 2011

The mineralocorticoid activity of 18-hydroxy-deoxycorticosterone (18-OH-DOC) was compared with that of deoxycorticosterone (DOC) and aldosterone in adrenalectomized adult female dogs. With respect to sodium retention, 18-OH-DOC was approximately five times less potent than DOC and 78 times less potent than aldosterone. With regard to the effect on potassium excretion 18-OH-DOC was 11 times less active than DOC and 615 times less than aldosterone.
Effect of P-chlorophenylalanine on the acquisition of tolerance to barbital
Authors: Lê Anh Dûng , Khanna Jatinder M. , Kalant Harold , LeBlanc A. Eugene
Published: April 2011

The effect of p-chlorophenylalanine (p-CPA) pretreatment on barbital tolerance in the rat as measured by motor impairment on the moving belt test was examined in two separate studies. The first used a 2 × 2 design with doses of p-CPA (125 mg/kg) or water, and sodium barbital (300 mg/kg) or water. The treatments continued for 28 days with tests every 7 days. The p-CPA dose used was previously shown to produce and maintain > 95% depletion of brain serotonin (5-HT). Tolerance developed to the test doses, and even greater tolerance to the chronic treatment doses. In both cases the p-CPA slowed the development of tolerance without altering the acute response to the challenge dose of barbital. The second study involved only a p-CPA-barbital group and a water-barbital group. In this case treatment lasted for up to 8 days, with separate subgroups being tested only once each at 2-day intervals, in order to prevent the tests from affecting the rate of tolerance development. This experiment confirmed that p-CPA slowed the development of barbital tolerance. The present findings provide additional support for the possibility that 5-HT may be involved in the development of tolerance to sedatives (e.g., alcohol, pentobarbital).
Potentiation of presynaptic inhibition of nociceptive pathways as a mechanism for analgesia
Authors: Sastry B. R.
Published: April 2011

In decerebrated spinal cats, stimulation of cutaneous Aδ and C afferents and intraarterial injections of bradykinin into a hind limb produced a reduction in the threshold for antidromic activation in the substantia gelatinosa of single C fibres. Meperidine increased the unconditioned threshold but potentiated the decrease in the threshold produced by Aδ fibre stimulation and by bradykinin injection. These results support the suggestion that myelinated cutaneous afferents can depolarize C afferent terminals. The observations also indicate that the depolarization of C afferent terminals produced during pain and by stimulation of other cutaneous afferents is potentiated by meperidine.
Renal blood flow distribution measured by microspheres during isovolemic hematocrit alteration in rats
Authors: Ackermann U. , Veress A. T. , Sonnenberg H.
Published: April 2011

The distribution of 15-μm microspheres was measured in rat kidneys before and after the animals had undergone either isovolemic hematocrit increase or isovolemic hematocrit decrease. Raising the systemic arterial hematocrit from 46 ± 1% (mean ± SEM) to 59 ± 1% caused a significant decrease in the rates of urinary sodium and potassium excretion [Formula: see text], but no significant changes in total renal blood flow (RBF), filtration fraction (FF), outer cortical flow, inner cortical flow, or rate of urinary volume excretion [Formula: see text]. Fractional sodium excretion was also unchanged suggesting that the decreased [Formula: see text] was the result of a decreased glomerular filtration rate (GFR). The measured decrease in GFR was not statistically significant. Lowering the systemic hematocrit from 45 ± 1% to 33 ± 1% caused a significant fall in FF as well as significant increases in the rate of urine volume excretion [Formula: see text], [Formula: see text], and GFR. There was a significant increase in RBF but again no change in the flow distribution between inner and outer cortex. The findings show that hematocrit alterations alone do not immediately lead to a redistribution of blood flow between inner and outer cortex of the rat kidney.
The effect of bicarbonate concentration on fatigue and recovery in isolated rat diaphragm muscle
Authors: Mainwood G. W. , Cechetto D.
Published: April 2011

Diaphragm strips from young rats (45–60 g) about 0.3 mm thick were fatigued by tetanic stimulation at a train repetition rate of 2 Hz for 3 min. The isometric tension developed was measured during fatigue and recovery in solutions containing 25, 10, or 2 mM bicarbonate at both 37 and 30 °C. Tension fell during fatigue to between 20 and 30% of the initial value and this was not significantly influenced by external bicarbonate concentration or temperature over the range considered. Recovery of tension was complete and rapid (t1/2 < 1 min) in 25 mM bicarbonate at both temperatures. In 10 and 2 mM bicarbonate recovery was slowed (t1/2 3.5 and 7 min, respectively, at 30 °C, 1.6 and 4.5 min at 37 °C) and incomplete (85 and 72% at 30 °C, 82 and 61% at 37 °C).Muscle creatine phosphate fell during fatigue but was completely restored within 4 min at 30 °C in either 2 or 25 mM HCO3. Lactate increased less in muscles fatigued in 2 mM HCO3 and fell at a slower rate during recovery. The results seem to exclude intracellular creatine phosphate concentration as a major determinant in recovery. The evidence suggests that external bicarbonate can affect the recovery of tension following fatigue by altering intracellular acid-base balance.
Reactivity of vasa deferentia from spontaneously hypertensive and normotensive Wistar rats
Authors: Corbett D. A. , Goldberg M. T. , Swamy V. C. , Triggle C. R. , Triggle D. J.
Published: April 2011

Vasa deferentia from age-matched spontaneously hypertensive rats (SHR) compared with three strains of control rats were found to be hyperresponsive to low concentrations, 10 and 20 mM, of KCl (K+) but not to noradrenaline (NA); the SHR tissue also demonstrated a lower ED50 to K+. Significant differences in maximum tension between SHR and the control animals in response to K+ were not seen although maximum tension developed to K+ was always greater than that developed to NA in either SHR or a control group. The loss of contractile response to K+ in the absence of extracellular calcium was more rapid in the SHR than in the control animals but no such difference was noted for the loss of response to NA. Differences in the Ca2+ dependence of KCl responses were found for 15- to 17-week-old SHR but not for 5- to 7-week-old SHR while differences in the Ca2+ dependence of the NA response were noted in the younger age group of SHR but were less evident compared with the K+ response in the older age group of rat. The 15- to 17-week-old SHR, but not 5- to 7- or 9- to 11-week groups, also demonstrated a hypersensitivity to Ba2+ whereas both SHR and normotensive control tissues demonstrated an extracellular Ca2+-independent and D 600 insensitive contractile response to lanthanum (La3+). The contractile response of the vas deferens to La3+ could, in part, be related to an effect of raised H+ but a pH-independent action of La3+ was also evident from studies with Tris-buffered solutions. Although the action of La3+ was similar in both SHR and control rats the SHR tissue was shown to be more sensitive to H+. The results demonstrate an altered threshold sensitivity and altered responsiveness of nonvascular smooth muscle in the SHR which parallels, in some respects, previous studies indicating altered vascular smooth muscle responsiveness to a variety of physiological and nonphysiological stimuli in the SHR. Furthermore, these studies may indicate that a generalized genetic alteration in the sensitivity of the smooth muscle cell to chemical stimulation and Ca2+ utilization may persist in the SHR. Whether such differences relate to the elevated blood pressure and etiology of hypertension is not yet clear.