bluuebunny/crossref_metadata_2025 huggingface dataset:
Micropipette analysis of the hemolytic stress of hypotonic erythrocytes: the influence of lipid-soluble compounds
Authors: Missirlis Y. F. , Fong F. , Brain M. C.
Published: April 2011

The technique of micropipette aspiration of individual erythrocytes has been used to determine the critical tension (Ter) for lysis of hypotonically slightly swollen normal erythrocytes and erythrocytes exposed to the influence of lipid-soluble chemical compounds. The value of Ter of preswollen normal erythrocytes was 12.23 ± 1.84 dyn/cm (1 dyn = 10 μN), a value which agrees well with that found by other workers. The Ter was increased in normal erythrocytes following exposure to four aliphatic alcohols, chloroform, and phenol. The optimal concentration resulting in 24–33% increase in Ter for the six compounds studied was very similar to the concentration previously found to be optimal in conferring increased resistance to osmotic hemolysis.The determination of Ter by micropipette aspiration of individual erythrocytes enables a range of concentrations of lipid-soluble compounds to be studied and led to the demonstration of a biphasic effect of the alcohols on the surface area elastic modulus.The studies now reported confirm the findings of Seeman (SEEMAN, P. 1972. The membrane action of anesthetics and tranquilizers. Pharmacol. Rev. 24(4), 583.) and suggest that incorporation of relatively short chain alcohols is concentration dependent and is associated with alterations in the mechanical-rheological properties of the membrane in a manner which appears analogous to the previously published reports on effects of alcohols on membrane transport and enzymatic activity. These findings suggest that lipid-soluble compounds at optimal concentrations influence both material properties and membrane-related functions, presumptively due to alterations in lipid–lipid, and (or) lipid–protein interactions.
Inability of glucagon to increase glomerular filtration rate in dogs with experimental cirrhosis and ascites
Authors: Levy Mortimer
Published: April 2011

In marked contradistinction to the normal dog, to the dog with renal hypoperfusion, or to the chronic caval dog with ascites, the intravenous infusion of glucagon at 5 μg/min to dogs with experimental portal cirrhosis and ascites does not increase glomerular filtration rate or renal blood flow. In eight experimental dogs who did not respond to glucagon, a marked natriuresis was observed in response to furosemide and a marked renal vasodilator response was seen following the intraarterial infusion of acetylcholine. Because plasma immunoreactive glucagon levels are increased fivefold in cirrhotic dogs, it is suggested that continuous high levels of this peptide render the animals insensitive to the effects of an exogenous infusion.
Motoneuronal after-potentials and extracellular divalent cations
Authors: Krnjević K. , Lamour Y. , MacDonald J. F. , Nistri A.
Published: April 2011

In cats under Dial anaesthesia, microiontophoretic injections of Co2+ or Mn2+ outside lumbosacral motoneurones regularly diminish the postspike hyperpolarizing after-potential (AHP) without any clear reduction of the deplorarizing after-potential (ADP). Comparable injections of Sr2+ have the opposite effect of augmenting the AHP. These results indicate that the AHP is indeed initiated by an influx of calcium linked to the action potential, but the ADP is unlikely to be mainly a manifestation of a calcium inward current.
Perfusions of the posterior hypothalamus of cats with various ions and saccharides: effects on body temperature
Authors: Jones D. L. , Veale W. L. , Cooper K. E.
Published: April 2011

Alterations of the ionic constituents of solutions perfused through the tissue of the posterior hypothalamic region in conscious cats elicited changes in body temperatures. Increasing the [Ca2+] to [Na+] ratio of the perfusion solution elicited falls in body temperature which were accompanied by changes in posture and vasomotor tone which assisted the heat loss. The magnitude of the fall was dependent on the ratio of [Ca2+] to [Na+] and was not related to the osmolarity of perfusion solution. The addition of dextrose to the perfusion solution attenuated or abolished the response produced by an increase in the [Ca2+] to [Na+] ratio. This dextrose effect could be attributed to its role as an energy substrate. These data are consistent with and extend previous suggestions that the set point for body temperature may be dependent on the inherent ratio of the ionic constituents of the posterior hypothalamic area. Further, they suggest that these ionically induced alterations can be overriden by increasing the available energy substrate.
Effect of autonomic agents on the amount of androgen- dependent granules in convoluted tubular cells of the mouse submandibular gland
Authors: Hosoi Kazuo , Aoyama Kazushi , Tomomura Akito , Ueha Takao
Published: April 2011

The convoluted tubular cells of the male mouse submandibular gland contain many serous-like granules in their apical cytoplasm. The autonomic regulation of the secretory process of the contents of these granules was studied by the following two methods: (1) immunochemical method using an antiserum specific to the granular components; and (2) histometric observations using light and electron microscopes. The results obtained by these two methods were well in agreement.When male mice were administered either phenylephrine or norepinephrine, the amount of granules in the glands significantly decreased. These two adrenergic stimulators were very effective, whereas synephrine was less effective. When mice were injected with a β-adrenergic agent (isoproterenol) or a parasympathomimetic agent (pilocarpine), the amount of granules in the glands did not change. The α-adrenergic blockers phenoxybenzamine and phentolamine almost completely neutralized the effect of α-adrenergic agents on the glands, whereas another α-blocker (ergotamine) was less effective. These facts suggest that the secretion of the granular components is mediated by way of α-adrenergic receptor sites in the glands.
Determination of the 'no effect' level of dietary parathion for the rat based on a short-term study
Authors: Davies Donald B. , Holub Bruce J.
Published: April 2011

Adult female rats (220–260 g) were fed a semipurified diet to which the pesticide parathion was either added or excluded. Dietary concentrations of parathion studied ranged between 0.5 and 20 ppm. At designated times following the initiation of treatment, control and treated animals were sacrificed for biochemical assessment. Routine investigations encompassed the determination of plasma cholinesterase activity using a highly sensitive radiometric assay. General nutritional evaluations included measurement of body weights and feed consumption during the growing period. In all studies, feeding parathion at the levels used produced no visible toxic manifestations. Final body weights and feed consumption of treated rats were comparable with control values in most cases. Data obtained from feeding trials of 1–25 days in duration indicated that reduction of plasma cholinesterase activity was most pronounced following 9–11 days of dietary parathion treatment (8 ppm). Feeding parathion at levels of 3.0 ppm or less for 11 days was without effect on plasma cholinesterase activity. Accordingly, the 'no effect' level of parathion for the female rat was judged to be 0.21 mg/kg body weight per day based on this short-term study. Using a safety factor of 100, this 'no effect' level translates into an 'acceptable daily intake' for humans of 2.1 μg parathion/kg body weight per day, which greatly exceeds levels reported to be ingested by Canadians.
Increased sensitivity of frog skeletal muscle to procaine in the presence of organic anions
Authors: Foulks J. G. , Perry F. A.
Published: April 2011

In solutions containing an organic anion in place of chloride, frog toe muscles displayed increased sensitivity to the local anaesthetic action of procaine. Twitch inhibition by procaine in all media was accompanied by suppression of action potentials without change in membrane resting potentials. The twitch depressant effect of procaine was greater in solutions with carboxylate anions than with alkyl sulfonates. The intensity and the rapidity of onset of the effects of organic anions was related to the size of their hydrophobic component.Procaine accentuated acetate-induced reductions in the [K]0 required to produce K contractures and in the time course of submaximum K contractures. These effects were not shared by benzocaine. They were antagonized by increased [Ca]0.The results indicate that separate agents can exert mutually enhancing actions from opposite surfaces of the sarcolemma to facilitate the inactivation of depolarization-induced excitation–contraction coupling as well as that of the potential-dependent sodium channel.
Synaptosomal uptake of norepinephrine and 5-hydroxytryptamine and synthesis of catecholamines during benzodiazepine treatment
Authors: Rastogi R. B. , Lapierre Y. D. , Singhal R. L.
Published: April 2011

Administration of diazepam (10 mg/kg, sc) acutely or for 22 consecutive days decreased spontaneous locomotor activity and presumably the release of norepinephrine and dopamine as evidenced by increased levels of these amines in crude synaptosomes and low levels of their metabolites, 4-hydroxy-3-methoxyphenylglycol in brain and homovanillic acid in striatum of rats. Acute or chronic diazepam elevated the levels of synaptosomal 5-hydroxytryptamine by 21 and 50%, respectively, suggesting that the release of this indoleamine was also diminished. Whereas a single injection of diazepam failed to alter the synaptosomal uptake of 5-[3H]hydroxytryptamine or rate of synthesis of this indoleamine, repeated exposure for 22 days enhanced it by 31 and 28%, respectively. Acute diazepam treatment also enhanced 5-hydroxyindoleacetic acid levels in hypothalamus, pons–medulla, and midbrain of rats. The endogenous level of tryptophan in P2 pellet also was increased (by 117%) in chronic diazepam-treated rats. Diazepam given acutely or chronically failed to change the rate of catecholamine synthesis. However, discontinuation of diazepam for 48 h in rats previously treated for 20 days significantly increased locomotor activity and synaptosomal catecholamine synthesis above the values of 'treated' as well as normal control animals. Despite their increased synthesis, the synaptosomal levels of norepinephrine and dopamine in 'withdrawn' groups were decreased to 46 and 62%, respectively. This could presumably be due to a compensatory release of these monoamines and partly to altered uptake of norepinephrine which was diminished by 24%. Additionally, the levels of homovanillic acid in striatum and 4-hydroxy-3-methoxyphenylglycol in brain were enhanced to 196 and 193%, respectively, taking the values of chronically exposed rats as 100%. Withdrawal of rats from diazepam decreased the rate of synthesis of 5-hydroxytryptamine and the level of 5-hydroxytryptamine within the crude synaptosomes; the latter could be attributed to enhanced release and impeded uptake of this indoleamine. The view gains support from enhanced levels of the metabolite 5-hydroxyindoleacetic acid seen in several brain areas of withdrawn rats.Our data suggest that diazepam exerts its central effects on mood and behaviour by impairing the release of catecholamines and 5-hydroxytryptamine. It is also suggested that enhanced release and decreased uptake of these monoamines may, in part, be responsible for the hyperexcitability seen during the 'rebound' phase in anxious patients withdrawn from benzodiazepine therapy.
Variations in serum dopamine β-hydroxylase in normal subjects and chronic alcoholics
Authors: Sellers Edward M. , Cooper Stanley D. , Roy Marie Lessard
Published: April 2011

Serum dopamine β-hydroxylase (DBH) activity varies greatly between individuals but is usually relatively constant within individuals. DBH activity was determined in 20 normal subjects and 6 chronic alcoholics during alcohol ingestion and withdrawal, under controlled and standardized conditions. For all subjects mean random DBH was 423 ± 249 (mean ± SD) nmol phenylethanolamine/h per millilitre serum. Between-day serum DBH values vary more than within-day values (21.1% vs. 15.1%). Cold-pressor testing or sudden standing does not increase mean DBH; however, some individuals show a significant increase which cannot be elicited on repeat testing. Mean DBH activity did not vary significantly over 24 h. Clinically useful correlations between single random DBH and blood pressure or 24-h urine catechols should not be expected.
Arterio–venous difference in lactate levels in myocardial Ischemia and reperfusion
Authors: Sharma G. P. , Das P. K. , Singal P. K. , Barwinsky J. , Cohen M. , Dhalla N. S.
Published: April 2011

The effects of 30-, 60-, and 90-min occlusion of the left anterior descending coronary artery and 60-min reperfusion were studied on the left ventricular dP/dt, myocardial ultrastructure, and tissue as well as blood lactate levels in dogs. The dP/dt was depressed by the occlusion, and reperfusion instituted after 30 min resulted in full recovery whereas that after 90 min had an adverse effect. Varying degrees of ultrastructural damage were noted after 60 and 90 min of occlusion and this was further exaggerated by reperfusion. Coronary occlusion markedly increased lactate content of ischemic myocardium, and the same returned to normal upon reperfusion. Myocardial ischemia for 30 or 60 min did not affect net arterial lactate extraction by the heart, but ischemia for 90 min reversed net lactate extraction to net lactate production by the heart. Reperfusion after 30 min of occlusion significantly increased lactate extraction, but reperfusion after 60 and 90 min of ischemia significantly decreased net lactate extraction and increased net production, respectively. The results indicate that estimation of net lactate exchange across the heart can be of value in assessing the viability of myocardium following coronary bypass surgery.
Effects of penicillin pretreatment on renal tubular para-aminohippurate transport in the immature rat
Authors: Noordewier B. , Withrow C. D.
Published: April 2011

The effect of pretreatment with penicillin on para-aminohippurate (PAH) transport by the kidney of the immature rat was evaluated in vivo. After 3 days of penicillin administration, renal clearances of inulin (CIN), PAH (CPAH), and the renal tubular transport maximum (Tm) for PAH were measured in rats as young as 17 days of age. The CPAH in 19- to 21-day-old rats pretreated with procaine penicillin was 54% greater than that of their littermate controls. Similarly, CPAH of rats that received sodium penicillin was 31% greater than control. CIN was not increased after penicillin pretreatment. Pretreatment of rats older than 24 days did not change CIN or CPAH. The Tm for PAH of 17-day-old rats pretreated with sodium penicillin was 51% greater than that of control rats. It was concluded that pretreatment with penicillin enhances the renal secretion of organic anions by the immature rat.
Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E1, E2, and I2 and penicillamine
Authors: Cunnane S. C. , Zinner H. , Horrobin D. F. , Manku M. S. , Morgan R. O. , Karmali R. A. , Ally A. I. , Karmazyn M. , Barnette W. E. , Nicolaou K. C.
Published: April 2011

Low concentrations of copper inhibited responses to norepinephrine and angiotensin (IC50 3 × 10−6 M) but not to potassium in rat mesenteric vascular preparations perfused either with buffer or indomethacin and prostaglandin (PGE2). The dose–response curve was not shifted by indomethacin, imidazole, or PGE2 but was moved to the right by 2.8 × 10−11 M PGE1 and to the left by 2.8 × 10−7 M PGE1. These effects of copper are similar to the effects of PGI2 in the preparation. Copper moved the PGI2 dose–response curve against noradrenaline in parallel to the left, suggesting that the two were interacting at some point. Penicillamine, which may stimulate PGE1 synthesis, had PGE1-like interactions with the copper effect, suggesting that its value in Wilson's disease may be partly due to antagonism of the biological action of copper as well as to its copper-chelating properties.
Cardiac muscarinic blocking and atropinic blocking effects of a tetramine disulfide with α-adrenoceptor blocking activity
Authors: Benfey B. G. , Yong M. S. , Belleau B. , Melchiorre C.
Published: April 2011

Since many α-adrenoceptor blocking drugs are known to have muscarinic blocking activity, BHC, a newly synthesized tetramine disulfide with α-adrenoceptor blocking activity, and two of its analogs were tested for muscarinic blocking activity in the isolated guinea pig atrium and ileum.BHC had muscarinic blocking activity. Its potency was higher in the atrium than in the ileum. The cardiac muscarinic blocking potency of the analog that contained carbon atoms instead of sulfur atoms was similar to that of BHC. Lower concentrations of the drugs antagonized inotropic effects of acetylcholine competitively, but higher concentrations had a smaller effect than expected for competitive antagonism.In the atrium BHC competitively inhibited the muscarinic blocking effect of atropine. Its atropinic blocking potency was smilar to the muscarinic blocking potency.Quinidine and gallamine also had muscarinic blocking and atropinic blocking effects in the atrium but were about 10 times less potent than BHC.
Subcellular effects of some anesthetic agents on rat myocardium
Authors: Lee S. L. , Alto L. E. , Dhalla N. S.
Published: April 2011

The effects of ether, chloroform, and halothane on calcium accumulation and ATPase activity of rat heart microsomes and mitochondria as well as on myofibrillar ATPase activity were investigated. Chloroform and halothane depressed microsomal and mitochondrial calcium uptake and binding in a parallel fashion. Ether decreased microsomal calcium binding and mitochondrial calcium uptake to varying degrees, while mitochondrial calcium binding was slightly enhanced. Whereas ether had no effect, chloroform depressed microsomal and mitochondrial total ATPase activities and halothane decreased microsomal ATPase and slightly stimulated mitochondrial total ATPase activities. Halothane was found to depress myofibrillar Mg2+-ATPase and ether was capable of decreasing myofibrillar Ca2+-ATPase. Chloroform was seen to inhibit both myofibrillar enzymes. These results suggest that the cardiodepressant actions of volatile anesthetic agents may be due to alterations in the calcium accumulating abilities of microsomal and mitochondrial membranes while direct myofibrillar effects may contribute to the depression seen with relatively higher concentrations of anesthetics.
Effects of morphine, naloxone, and diallylnormorphine upon behaviour maintained by electric-shock postponement in squirrel monkeys
Authors: Stretch Roger , Sanchez-Ramos J. R.
Published: April 2011

The effects of morphine, naloxone, and diallylnormorphine were examined on the continuous, electric-shock postponement behaviour of the squirrel monkey. Under this schedule, a lever-pressing response postponed the delivery of brief electric shocks delivered to the monkey's tail. Dose–response curves were determined for morphine (0.3–10 mg/kg, im) and naloxone (0.1–10 mg/kg, im), separately. Naloxone (0.1–3 mg/kg, im) and diallylnormorphine (0.1–3 mg/kg, im) antagonized the acute rate-suppressive effect of morphine given at a dose of 10 mg/kg. Naloxone was found to be approximately 10 times more potent than diallylnormorphine in reversing the acute suppression of responding induced by morphine. In subsequent experiments, monkeys received morphine (10 mg/kg, im) on a daily basis, each injection being given 5 min prior to behavioural testing. The rate-suppressive effect of morphine diminished over a series of 10 consecutive sessions, indicating the development of tolerance to this effect of morphine. Naloxone (0.1–3 mg/kg, im), given in conjunction with morphine, in morphine-tolerant monkeys produced dose-dependent increases in responding that greatly exceeded overall rates seen during reversal of the acute effects of morphine or naloxone tested prior to the induction of tolerance at identical doses. These monkeys become extremely agitated, vomiting was often seen, and contorted postures were evident; despite signs of antagonist-precipitated abstinence, response rates usually exceeded 1/s when naloxone was given in conjunction with morphine (10 mg/kg, im) at doses of 1 or 3 mg/kg, im. These results illustrate the sensitivity of operant responding maintained by a schedule of electric-shock postponement to assess the development of morphine tolerance accompanied by low-grade physiological dependence in the squirrel monkey.
Bicarbonate-activated ATPase activity in renal cortex of chronically acidotic rats
Authors: Cole Craig H.
Published: April 2011

The effect of chronic NH4Cl-induced acidosis on the activity of a bicarbonate-activated component of ATPase was studied in homogenates of renal tissue from Wistar rats. This particular component of ATPase, which is maximally stimulated by 50 mM bicarbonate, and is insensitive to the action of ouabain, has been implicated in the active transport of bicarbonate in various tissues. The activity of this enzyme in cortical homogenates from an acidotic group of animals was 4.3 ± 0.4 μmol Pi/mg protein per hour compared with 5.8 ± 0.3 μmol Pi/mg protein per hour in a control group (p < 0.02). No significant change in bicarbonate ATPase activity was observed in medullary homogenates, and NaK-ATPase activity remained the same in cortex and medulla of both groups. Subcellular fractionation of the cortical tissue homogenates revealed that bicarbonate ATPase activity in a microsomal fraction from acidotic animals was 6.5 ± 1.1 μmol Pi/mg protein per hour compared with 9.4 ± 1.2 μmol Pi/mg protein per hour in control animals (p < 0.02). Bicarbonate ATPase activity in other subcellular fractions was not different in the two groups of animals. These findings are compatible with the hypothesis that a certain percentage of bicarbonate reabsorption in the nephron is mediated by a bicarbonate-activated component of ATPase.
A study of the chemical binding of allyl isothiocyanate with thyroxine and of the effect of allyl isothiocyanate on lipid metabolism in the rat
Authors: Muztar A. Jabbar , Ahmad Parvez , Huque Taufiqul , Slinger S. J.
Published: April 2011

Two experiments were conducted with allyl isothiocyanate (AITC): one in vitro, to investigate the chemical binding of AITC with thyroxine (T4), tyrosine (Tyr), and leucine (Leu), and the other in vivo, to evaluate the effect of AITC on the blood clotting mechanism and on the protein and lipid contents of rat liver. The in vitro study, which used the techniques of ultraviolet spectroscopy and thin-layer chromatography, indicated the formation of a complex of AITC with T4 and Tyr but not with Leu. The presence of a phenyl ring with an OH group at the position para to the alanine side chain is suggested as a prerequisite for the chemical binding of AITC with amino acids. The in vivo experiment involved administration of AITC, T4, or the ALTC–T4 complex by the intraperitoneal route to young male Sprague–Dawley rats for 30 days. AITC exhibited a strong coagulant effect, which was seemingly mediated by the relatively high plasma phospholipid concentration. T4 and the AITC–T4 complex were without a significant effect on blood coagulation. AITC was without effect on liver protein but increased cholesterol, phospholipid, and total lipid contents markedly. The effect of T4 on the liver protein and lipids was not significant. The AITC-T4 complex caused a significant increase in the liver protein and an intermediate rise in the lipids compared with AITC. The increase in plasma and liver lipid concentrations caused by AITC was probably related to increased hepatic lipid production and decreased clearance of the circulating lipids.
Characterization of receptors for angiotensin in the rat vas deferens
Authors: Magnan J. , Regoli D.
Published: April 2011

Experiments were performed in the rat vas deferens to characterize the receptor for angiotensin mediating the potentiation of the sympathetic nerve stimulation by this peptide. For this purpose we measured the order of potency of various angiotensins, the affinity of two specific and competitive antagonists, and we compared the effects of several angiotensins in tissues desensitized by angiotensin II.The potency of natural angiotensins follows the order: ATII > ATI > ATIII the relative potency of a few analogues which resist degradation by proteolytic enzymes as well as the potency of three L-Ala analogues of ATII show similar changes as those observed in other smooth muscle preparations (e.g. the rabbit aorta).Affinity of antagonists was evaluated by measuring pA2 and is higher for [Leu8]-ATII than for [des-Asp1, Leu8]-ATII. Both antagonists appear to be competitive since they displace the dose-response curves of ATII and ATIII to the right without changing the slope of the curves. Desensitization with ATII renders the tissues insensitive to ATIII and to other angiotensins without changing the response of the tissues to substance P.ATII does not modify the action of exogenous NA on nonstimulated tissues. ATI has no direct effect since its action is completely blocked in the presence of an inhibitor of the converting enzyme (SQ. 14225), while the responses of the vas deferens to ATII and substance P are unaltered.It is concluded that the receptor for ATII in the rat vas deferens is of the same type as the receptor mediating contraction of the rabbit aorta.
Correction factor for the estimation of plasma glucose synthesis from the transfer of 14C-atoms from labelled substrate in vivo: A preliminary report
Authors: Hetenyi Jr. G.
Published: April 2011

Based on a previously designed method for the estimation of the contribution of C-atoms by acetylcoenzyme A to the hepatic oxaloacetate pool, the loss of 14C-atoms on their way from a precursor to plasma glucose due to 'metabolic exchange' was estimated in normal and diabetic dogs and in normal rats. Due to this loss of 14C-atoms, the rates of gluconeogenesis when calculated from the transfer of 14C-atoms from precursors (other than glycerol) are underestimated by a factor of 2.2 ± 0.07 in normal, 1.8 ± 0.05 in diabetic dogs, and by 1.55 ± 0.04 in normal rats.
The origin of two components in contraction of guinea pig papillary muscle in the presence of noradrenaline
Authors: Bogdanov Konstantin Y. , Zakharov Sergey I. , Rosenshtraukh Leonid V.
Published: April 2011

In experiments on isolated guinea pig papillary muscles the effects of verapamil (5 mg/L) and caffeine (1 g/L) on the two-component contraction were investigated. The muscles were continuously superfused with normal Tyrode's solution containing 2 mg of noradrenaline/L at 20–22 °C. The first derivative of contractile response and transmembrane action potential were simultaneously recorded. Verapamil suppressed the amplitude of the second component and had no influence on the first component of contraction. Caffeine eliminated the first component and increased the second component of contraction. It was suggested that in the activation of two-component contraction calcium ions from two different pools take part: (1) those released from sarcoplasmic reticulum, and (2) those that crossed a cell membrane during the plateau of the action potential.
Effects of unilateral orchidectomy on rat epididymal Δ4-5α-reductase and 3α-hydroxysteroid dehydrogenase
Authors: Robaire B.
Published: April 2011

The effects of unilateral orchidectomy on the adult rat epididymal testosterone metabolizing enzymes, Δ4-5α-reductase and α-hydroxysteroid dehydrogenase, are investigated. Five weeks following unilateral orchidectomy, it is found that the activity of 3α-hydroxysteroid dehydrogenase per organ is not altered, whereas Δ4-5α-reductase activity decreased by more than 80% on the side of the orchidectomy. Neither accessory sex tissue weights, ventral prostate and seminal vesicles, nor the concentration of circulating testosterone, luteinizing hormone, follicle-stimulating hormone, or prolactin is altered by unilateral orchidectomy. These data indicate that (1) epididymal 3α-hydroxysteroid dehydrogenase activity can be maintained by circulating androgens and that (2) the major factor regulating Δ4-5α-reductase activity is not a substance secreted by the testes into the peripheral circulation. It is suggested that a substance directly secreted into the epididymis by the testis regulates epididymal Δ4-5α-reductase activity.
Neural activation of α-adrenoreceptors in glucose mobilization from liver
Authors: Lautt W. Wayne
Published: April 2011

Using a newly described method for obtaining pure, mixed hepatic venous blood samples, it was demonstrated that glucose mobilization from the liver of the anesthetized cat in response to hepatic nerve stimulation is via α-adrenergic receptors. Neither the elevation of portal pressure nor the amount of glucose generated by the liver was affected by intraportal administration of 1 mg propranolol/kg (β blockade). In the presence of α-receptor blockade (3 mg phentolamine/kg) the portal venous pressure change was minor and the glucose output actually decreased slightly upon nerve stimulation, a response consistent with our previously demonstrated reduction of glucose output by parasympathetic nerve stimulation. The present responses to nerve stimulation were not due to activation of pancreatic nerves since these nerves were routinely ligated.
Metabolism of the isolated perfused rabbit heart. III. Energy stores and creatine kinase release during prolonged reoxygenation and atrial pacing
Authors: Chiong Miguel A. , Winton Timothy L.
Published: April 2011

When the perfused rabbit heart is reoxygenated for 75 min after 25 min of anoxic perfusion, left ventricle performance stabilizes at 50% of control levels, but the rate of creatine kinase (CK) release is high (1.9 U/min) and ATP stores are low (5 μmol/g dry weight). These results suggest that the preparation is on the verge of severe failure. This possibility was investigated by following the recovery for an extra 60 min of reoxygenation and by stressing the hearts with atrial pacing.The data show that no deterioration occurred during the extra recovery period; on the contrary, mechanical performance remained stable, while the rate of CK release fell to 1.1 U/min, and ATP stores increased by 204%. In aerobic hearts, pacing increased the product of left ventricular systolic pressure (LVSP) and heart rate, myocardial uptake of oxygen [Formula: see text], coronary sinus flow, and O2 extraction, but LVSP and [Formula: see text] per beat fell. Similar responses were seen in postanoxic hearts, but LVSP improved during pacing while the rate of CK loss declined and ATP stores increased. These metabolic changes were inversely related to the rate of contraction. It is concluded that the preparation was not deteriorating at 75 min of reoxygenation, and that its metabolism was improved by cardiac pacing.
Mg2+–Ca2+–Na+ interactions in uterine smooth muscle: Studies with cAMP
Authors: Meisheri Kaushik D. , McNeill John H.
Published: April 2011

The influence of variation in the extracellular concentrations of Na+, Mg2+, and Ca2+ in the depolarizing medium on isoproterenoi-induced increases in cAMP levels and relaxation was studied in rat uterus. Isoproterenol (10−8 M) failed to increase cAMP levels in the high-K+ medium containing no Na+. When 80 mM Na+ was present in the medium, isoproterenol caused increases in cAMP levels similar to those observed in nondepolarized uterus. A similar effect of 2.5 mM Mg2+ was observed on the cAMP response. These effects of Na+ and Mg2+ were antagonized by increasing the extracellular concentration of Ca2+. The simultaneous presence of 80 mM Na+ and 2.5 mM Mg2+ did not produce an additive effect on the cAMP responses. The relaxation responses to isoproterenol were not significantly altered in the above experiments. The results are consistent with our previous suggestion that the observed effect of Na+ and Mg2+ on the cAMP response is mediated indirectly by inhibiting Ca influx occurring during depolarization.
The stiffness of slow-twitch muscle lags behind twitch tension: Implications for contractile mechanisms and behavior
Authors: Stein R. B. , Parmiggiani F.
Published: April 2011

Small, square stretches were applied during contractions of soleus and plantaris muscles in the cat to measure muscle stiffness. The stiffness of the slow-twitch soleus muscle (but not of the fast plantaris muscle) reaches a maximum after the peak in twitch tension. Since the number of active bonds should be maximum before the peak in tension, we suggest that many bonds are in the rigor state during the falling phase of the twitch. The stiffness of the bonds in this state may be useful for prolonging the twitch in slow-twitch muscles and for maintaining a posture.
Hepatic glycogen formation by direct uptake of glucose following oral glucose loading in man
Authors: Radziuk J.
Published: April 2011

The extent of direct uptake of glucose into hepatic glycogen following oral glucose loading in man is determined by mobilizing newly formed glycogen with a glucagon infusion in the immediately postabsorptive period. The amount of glucose flushed from liver glycogen is measured by using "out-of-steady-state" tracer turnover techniques. Following a 93 ± 1 g load of glucose, at most 7.7 ± 1 g of the ingested glucose is recovered from glycogen. If the unlabelled glucose pool is taken into account, at most 10 g of available glucose can be said to be taken up directly into hepatic glycogen during the absorption of the glucose load.
Norepinephrine, monoamine oxidase, and acetylcholinesterase in the rat jugular vein compared with other blood vessels
Authors: Cohen Marlene L. , Landry Ann S. , Hemrick Susan K. , Fuller Ray W.
Published: April 2011

The observation that the rat jugular vein relaxed in response to norepinephrine but not to field stimulation prompted us to evaluate the extent of innervation in this tissue. The norepinephrine concentration in the jugular vein was about 10% of that in the mesenteric artery and vein. The low levels of norepinephrine were not due to higher monoamine oxidase activity relative to the enzyme activity in other blood vessels. In the jugular vein, as in heart and brain, serotonin was the preferred substrate for monoamine oxidase whereas in the femoral vein, mesenteric vein, and mesenteric artery, phenylethylamine oxidation was greater. Based on kinetic and inhibitory studies with LY51641, a selective type A inhibitor, monoamine oxidase activity was not found to be uniform throughout the cardiovascular system. In addition to low levels of norepinephrine, acetylcholinesterase activity in the jugular vein was only 5 and 13% of the activity in the portal vein and mesenteric artery, respectively. Thus, we provide strong evidence that our inability to generate a response to field stimulation in the rat jugular vein results from the lack of functional innervation in this tissue. This information adds to the usefulness of this preparation for comparative studies of agents acting on the smooth muscle without the added complication of neuronal uptake mechanisms.
Inhibition of kindling-induced generalized seizures by aminooxyacetic acid
Authors: Salle Gildas Le Gal La
Published: April 2011

The anticonvulsant effect of aminooxyacetic acid (AOAA) was examined on a model of experimental epilepsy (kindling) induced by daily appropriate amygdaloid stimulation in the rat. Doses from 5 to 30 mg/kg were intraperitoneally administered in fully kindled animals 3–4 h before triggering a seizure. At low doses (< 15 mg/kg) AOAA had no effect whereas at higher doses (> 15 mg/kg) it reduced the severity of the generalized kindled seizures in over half the cases, and even sometimes completely blocked them. The inhibition of epileptic activity by AOAA is in accordance with the hypothesis that an increase in GABA level is associated with a reduction of epileptic sensitivity. An unexpected lengthening of the afterdischarge duration was also observed in about 20% of the cases, independently of the amount administered. This fact is discussed in regard to the complex action of AOAA on -γ-aminobutyric acid related enzymes.Finally, since the afterdischarge threshold was shown to be unaffected by the drug, it is suggested that it may act on the afterdischarge propagation rather than at the focal amygdaloid level.
Kinetics of ADP-induced human platelet shape change: apparent positive cooperativity
Authors: Milton John G. , Yung W. , Glushak C. , Frojmovic M. M.
Published: April 2011

The kinetics of ADP-induced human platelet shape change have been examined. Initial velocities of platelet shape change were estimated by two methods: (1) the slope of the initial decrease in light transmission through stirred, citrated platelet-rich plasma, and (2) direct examination of platelet morphologies by phase-contrast microscopy. In both cases, a value of the Hill coefficient, NH, significantly greater than 1 is obtained (2.0 ± 0.2 and 1.8 ± 0.2, respectively). The observed elevated value of NH is not due to a substantial fraction of the ADP being platelet bound, the presence of factors in the plasma, platelet heterogeneity, or the influence of the rate of platelet shape change reversion. Our observations suggest that ADP-induced platelet shape change may be a positively cooperative or "threshold" type response.
The responses of carotid vascular strips from spontaneously hypertensive and normotensive rats
Authors: Swamy V. C. , Triggle D. J.
Published: April 2011

The responses to noradrenaline (NA) and KCl of carotid arterial strips from spontaneously hypertensive rats (SHR) and three strains of normotensive rats (NR) were compared using tissues obtained from young (5–7 weeks) or older (15–17 weeks) rats. The maximum responses and sensitivity of strips from SHR were less than those of NR in both age groups. Relaxation of maximum NA-induced responses was consistently faster, and relaxation of KCl-induced responses generally slower with strips from SHR. Carotid strips from young SHR showed a greater dependence on extracellular calcium in their responses to NA and a lesser dependence in their KCl-induced responses than tissues from NR. We conclude that the smooth muscle of carotid arteries from SHR differs intrinsically from that of NR and that the differences in vascular responses may be related to altered excitation-contraction processes in the SHR.
Regional distribution of sodium acetylsalicylate in the brain of normothermic and hyperthermic rabbits
Authors: Lin M. T. , Hoo S. L.
Published: April 2011

This study was designed to determine regional distribution of sodium acetylsalicylate in the brain of normothermic rabbits, rabbits with hyperthermia induced by pyrogen administration, and rabbits with hyperthermia induced by infrared irradiation. Increasing body termperature with either leucocytic pyrogen or infrared light irradiation about doubled the concentration of sodium acetylsalicylate in four regions of the brain. This suggests a more rapid penetration of sodium acetylsalicylate into the brain under hyperthermic conditions. This may explain why the drug lowers body temperature more effectively in febrile animals than in febrile animals.
A positive inotropic response of guinea pig isolated atria to histamine not mediated via H1 or H2 receptors
Authors: Wilson Campbell , Broadley Kenneth J.
Published: April 2011

The positive chronotropic responses of guinea pig isolated right atria to histamine were antagonized by metiamide (pA2, 5.95) thus confirming their H2 receptor classification. The positive inotropic responses of paced left atria were antagonized to some extent by mepyramine to give a pA2 value of 7.87, indicating the involvement of H1 receptors. A limit to the shift of cumulative dose–response curves for the inotropic response suggested an H1 receptor resistant component. The inotropic response to sequentially administered histamine was biphasic. On lowering the temperature to 25 °C, the two components became more demarcated and separated by a negative phase. Only the primary positive component and the negative component were antagonized by mepyramine. At 38 °C, the response was similarly converted to a monophasic one. The residual responses were resistant to metiamide and propranolol antagonism and therefore not mediated via H1, H2, or β-adrenergic receptors.
Calcium antagonistic drugs. Mechanism of action
Authors: Church Jon , Zsotér Thomas T.
Published: April 2011

Calcium antagonists represent a new class of drugs, which were suggested to act by a selective inhibition of Ca2+ influx through cell membranes. We studied the mechanism of action of three calcium antagonists, diltiazem, nifedipine, and verapamil, by investigating the effect on 45Ca uptake and efflux in rat heart and aorta and in rabbit vessels. The upake of La3+-resistant 45Ca was not decreased by nifedipine or verapamil either in the heart or in the vessels and was increased by diltiazem in rabbit vessels. The efflux of 45Ca from the mesenteric vein of rabbit, originating presumably from intracellular and membrane-bound fractions, was enhanced by nifedipine. These effects were observed with drug concentrations inhibiting contractions in isolated atria and the spontaneous and norepinephrine-, potassium-, or barium-induced contractions in the portal vein of rats. Thus, our results suggest that calcium antagonistic drugs act by other mechanisms than the inhibition of transmembranous Ca flux, probably on the release and binding of Ca2+ in intracellular pools. The relatively greater inhibition of norepinephrine- than K+-induced contractions in vessels by the calcium antagonistic drugs and the abolition of the inotropic effect of norepinephrine in rat atrium exposed to 0-Ca Krebs solution for a short period are other effects suggesting an intracellular action for these drugs.
The transient contractile response of the isolated rat tail artery to inhibition of the sodium pump
Authors: Palatý Vladimír
Published: April 2011

The isolated rat tail artery responds to incubation in 1 mM ouabain containing, K-free physiological salt solution by transient contraction which is due to release of endogenous catecholamines. The eventual decline in active tension cannot be attributed solely to the decreasing rate of release of endogenous catecholamines, for the latter remains quite high even after the preparation has relaxed completely. It seems, therefore, that the relaxation is due also to the substantial decrease in the responsiveness of smooth muscle cells to (−)-norepinephrine that accompanies dissipation of the transmembrane gradients of Na+ and K+.
Biphasic activity of membrane-bound enzymes in brain mitochondria and synaptosomes during the development of tolerance to and physical dependence on chronic morphine administration to rats
Authors: Hosein E. A. , Lapalme Marc , Lau Allan , Wan Ophelia , Stefanysyn Henry , Zucker Joyce
Published: April 2011

Male Sprague–Dawley rats were given morphine intraperitoneally ranging from 20 mg/kg on day 1 to 220 mg/kg on day 7 for the development of tolerance to, and on withdrawal, physical dependence on the drug. At 0.5, 6, 24, and (or) 48 h following opiate treatment on days 1, 3, 5, and 7, brain mitochondria and synaptosomes were harvested and assayed for Mg2+-stimulated ATPase, acetylcholinesterase, malate dehydrogenase, and NaF-stimulated adenylate cyclase activity.During the period of morphine administration, the experimental group gained weight at a lower rate than the controls and the rectal temperature increased from 37.2 to 39.6 °C. Between 24 and 48 h after withdrawal following 7 days of drug treatment, there was at least 10% weight loss in all animals and the rectal temperature fell to 37.5 °C.Assay of the membrane-bound NaF-stimulated adenylate cyclase from synaptosomes and Mg2+-stimulated ATPase from mitochondria at 0.5 h following drug administration during the development of tolerance showed that the immediate and significant inhibitory effect of the drug on the enzymes diminished to 0 as the daily dosage was increased. The discontinuity temperature of Mg2+-stimulated ATPase decreased from 16.9 to 13.3 °C, an effect which was obtained even on day 7 of drug treatment when enzyme activity had returned to normal. Assay of these enzymes 48 h following chronic drug treatment during the development of a withdrawal reaction showed an increase in their activities. A partial reversal in the discontinuity temperature with Mg2+-ATPase was also observed at the time of assay.Synaptosomal acetylcholinesterase and mitochondrial malate dehydrogenase were unaffected by the drug treatment throughout the period of the study.The fluorescence observed on interaction of 1-anilino-8-naphthalene sulfonate (ANS) with either the synaptosomal or mitochondrial membranes harvested 0.5 h after drug treatment showed a significant decrease on day 1. However, this effect was abolished by day 7 of drug treatment. The difference in fluorescence produced with membranes harvested 0.5 h following the first dose of drug on day 1 and those 48 h after the last dose on day 7 was also very significant.The results showed that during the development of tolerance to, and physical dependence on, morphine there were nonspecific biphasic alterations in membrane-bound enzyme activity and the fluorescence produced on interaction with ANS. It is suggested that these effects were brought about by adaptive changes taking place simultaneously in the membrane lipid components of the brain subcellular particles studied.
Effect of perfusate Ca2+ on the relation between metabolism and mechanical performance in the rat heart
Authors: Snow T. Russell , Rubanyi Gabor , Dora Tunde , Dora Eörs , Kovach Arisztid G. B.
Published: April 2011

Langendorf perfused rat hearts (n = 25) were used to study the effects of changes in perfusate Ca2+ concentration ([Ca2+p]) on the relation between metabolism and mechanical performance with either glucose or pyruvate as the exogenous substrate. Increased [Ca2+p] (from 1.3 to 3.9 mM) produced an increase (243 ± 38%) in left ventricular developed pressure regardless of the substrate. With glucose as the substrate, the NADH fluorescence intensity increased by 11.8 ± 1.2% (n = 17) relative to control indicating a more reduced state of the respiratory chain. Increasing [Ca2+p] in the pyruvate perfused heart produced the expected NADH oxidation (−6.2 ± 1.1%; n = 8). Hence the change in NADH fluorescence associated with increased [Ca2+p] is substrate dependent. The data show that, with glucose as the substrate but not with pyruvate, increases in [Ca2+p] increase the availability of reducing equivalents to the respiratory chain above the level necessary to compensate for the increased demand resulting from the greater contractile performance.
Development of membrane conductance of chick skeletal muscle in culture
Authors: Thomson C. M. , Dryden W. F.
Published: April 2011

Resting membrane potentials and membrane conductances of chick skeletal muscle in culture were determined from the 3rd to the 10th day after plating. The effect of tetraethylammonium (TEA) and of replacement of potassium with caesium on these parameters was investigated. Resting membrane potential (Em) rises during myogenesis in vitro and resting membrane conductance (Gm) falls. The initial level of Gm was relatively high (1.2 mS cm−2) but this fell to a final level around 0.2 mS cm−2. The most rapid changes in both parameters occurred between days 3 and 5 of culture. Both TEA and caesium depressed Em and Gm at all stages of development. On the 3rd day of culture Gm was reduced by 0.2 mS cm−2 by both agents. Thereafter, Gm was depressed by about 0.1 mS cm−2. Caesium does not penetrate potassium channels and the reduction in Gm is attributed to block of these channels. This indicates that resting potassium conductance is relatively constant at 0.1 mS cm−2 throughout muscle fibre development. Because TEA produces changes in Gm similar to those produced by caesium, TEA is concluded to be acting at the potassium channel in a manner similar to caesium.