bluuebunny/crossref_metadata_2025 huggingface dataset:
The expression, regulation and signal transduction pathways of the mammalian gonadotropin-releasing hormone receptor
Authors: Cheng Kwai Wa , Leung Peter CK
Published: April 2011

Normal mammalian sexual maturation and reproductive functions require the integration and precise coordination of hormones at the hypothalamic, pituitary, and gonadal levels. Hypothalamic gonadotropin-releasing hormone (GnRH) is a key regulator in this system; after binding to its receptor (GnRHR), it stimulates de novo synthesis and release of gonadotropins in anterior pituitary gonadotropes. Since the isolation of the GnRHR cDNA, the expression of GnRHR mRNA has been detected not only in the pituitary, but also in extrapituitary tissues, including the ovary and placenta. It has been shown that change in GnRHR mRNA is one of the mechanisms for regulating the expression of the GnRHR. To help understand the molecular mechanism(s) involved in transcriptional regulation of the GnRHR gene, the 5' flanking region of the GnRHR gene has recently been isolated. Initial characterization studies have identified several DNA regions in the GnRHR 5' flanking region which are responsible for both basal expression and GnRH-mediated homologous regulation of this gene in pituitary cells. The mammalian GnRHR lacks a C-terminus and possesses a relatively short third intracellular loop; both features are important in desensitization of many others G-protein coupled receptors (GPCRs), Homologous desensitization of GnRHR has been shown to be regulated by various serine-threonine protein kinases including protein kinase A (PKA) and protein kinase C (PKC), as well as by G-protein coupled receptor kinases (GRKs). Furthermore, GnRHR was demonstrated to couple with multiple G proteins (Gq/11, Gs, and Gi), and to activate cascades that involved the PKC, PKA, and mitogen-activator protein kinases. These results suggest the diversity of GnRHR-G protein coupling and signal transduction systems. The identification of second form of GnRH (GnRH-II) in mammals adds to the complexity of the GnRH-GnRHR system. This review summaries our recent progress in understanding the regulation of GnRHR gene expression and the GnRHR signal transduction pathways.Key words: gonadotropin-releasing hormone receptor, transcriptional regulation, desensitization, signal transduction.
Factors controlling ovarian apoptosis
Authors: Andreu-Vieyra C V , Habibi H R
Published: April 2011

Apoptosis is a form of programmed cell death that is essential for the development of the embryo and adult tissue plasticity. In adults, it is observed mainly in those tissues undergoing active differentiation such as the hematopoietic system, testis, ovary, and intestinal epithelium. Apoptosis can be triggered by many factors, such as hormones, cytokines, and drugs, depending on the type of the cell. While the intracellular signaling mechanisms may vary in different cells, they all display similar morphological and biochemical features at the later stages of the apoptotic process. This review focuses on the factors controlling ovarian apoptosis, emphasizing observations made on GnRH-induced apoptotic process in goldfish follicles.Key words: apoptosis, ovary, GnRH.
Uptake properties of lamivudine (3TC) by a continuous renal epithelial cell line
Authors: Leung Simon , Bendayan Reina
Published: April 2011

The purpose of this study was to characterize the renal uptake properties of the cytidine analog and antiretroviral agent 3TC. The uptake of radiolabelled 3TC was measured at 37°C in a continuous porcine renal epithelial cell line (i.e., LLC-PK1cells) grown as a monolayer on an impermeable support. 3TC (5 µM) uptake (37°C) by the monolayer cells was saturable (Km= 1.2 ± 0.2 mM) but not significantly altered by various dideoxynucleoside analog drugs, nucleosides, and nucleoside transport inhibitors, suggesting that a nucleoside transporter is not involved in 3TC uptake. A number of endogenous organic cation probes and inhibitors significantly reduced 3TC uptake by the monolayer cells. Quinine, trimethoprim (TMP), and tetraethylammonium (TEA) inhibited 3TC uptake in a dose dependent manner with IC50values of 0.6mM, 0.63mM, and 1.9 mM, respectively. In turn, the uptake of the typical organic cation substrate TEA was inhibited by high concentrations of 3TC. An outwardly directed proton gradient significantly increased the uptake of 3TC by the monolayer cells, suggesting the involvement of a proton exchange process. Conversely, in the presence of monensin, a Na+/H+ionophore, the uptake of 3TC was significantly reduced. These results suggest that the uptake of 3TC by a cultured renal epithelium may be mediated by an organic cation-proton exchanger. The observed clinical interaction between 3TC and trimethoprim may be explained by competition for a common renal organic cation tubular transporter.Key words: 3TC, kidney, uptake, LLC-PK1, tubular elimination.
Interaction between nitric oxide and renal myogenic autoregulation in normotensive and hypertensive rats
Authors: Wang Xuemei , Cupples William A
Published: April 2011

Blood pressure fluctuates continuously throughout life and autoregulation is the primary mechanism that isolates the kidney from this fluctuation. Compared with Wistar rats, Brown Norway (B-N) rats display impaired renal myogenic autoregulation when blood pressure fluctuation is increased. They also are very susceptible to hypertension-induced renal injury. Because blockade of nitric oxide augments myogenic autoregulation in Wistar rats, we compared the response of the myogenic system in B-N rats to nitric oxide blockade with that of other strains [Wistar, Sprague-Dawley, Long-Evans, spontaneously hypertensive (SHR)]. Renal blood flow dynamics were assessed in isoflurane anesthetized rats before and after inhibition of nitric oxide synthase by Lω-nitro-arginine methyl-ester (L-NAME, 10 mg/kg, iv). Under control conditions, myogenic autoregulation in the B-N rats was weaker than in the other strains. Myogenic autoregulation was not augmented after L-NAME administration in the SHR, but was augmented in all the normotensive rats. The enhancement was significantly greater in B-N rats so that after L-NAME the efficiency of autoregulation did not differ among the strains. The data suggest that nitric oxide is involved in the impaired myogenic autoregulation seen in B-N rats. Furthermore, the similarity of response in Wistar, Long-Evans, and Sprague-Dawley rats suggests that modulation by nitric oxide is a fundamental property of renal myogenic autoregulation.Key words: renal blood flow, transfer function, dynamics, SHR, Wistar, Long-Evans, Sprague-Dawley, Brown-Norway, L-NAME.
Relationship between extra and intracellular sources of calcium and the contractile effect of thiopental in rat aorta
Authors: Henkel Carlos Castillo , Asbun Juan , Ceballos Guillermo , Castillo María del Carmen , Castillo Enrique F
Published: April 2011

To evaluate the relationship between the vasocontractile effect of thiopental and the extra and intracellular sources of Ca2+, we analyzed both the contractile effect of the barbiturate on rat aortic rings and its ability to modify the intracellular calcium concentration in cultured rat aorta smooth muscle cells. Thiopental (10310 µg/mL) contracted aortic rings only in the presence of extracellular Ca2+, and this effect was not blocked by verapamil or diltiazem. On the contrary, Ca2+(0.13.1 mM) evoked contractions only when thiopental (100 µg/mL) was present. Although in calcium-free solution thiopental (100 µg/mL) did not contract aortic rings, it abolished the contractile effect of either phenylephrine (106M) or caffeine (10 mM). Finally, thiopental augmented the intracellular calcium concentration in cultured smooth muscle cells incubated either in the presence or absence of calcium. In conclusion, thiopental's vasocontractile effect depends on extracellular calcium influx, which is independent of L-calcium channels. The increase in intracellular Ca2+concentration elicited by thiopental in Ca2+-free solution and its ability to block the effect of phenylephrine and caffeine suggest that this barbiturate can deplete intracellular pools of calcium. Therefore, the calcium entry pathway associated with the contractile effect of thiopental may correspond to the capacitative calcium entry model.Key words: smooth muscle, Ca2+kinetics, vasoconstriction.
Proteinase-activated receptor 4 (PAR4): activation and inhibition of rat platelet aggregation by PAR4-derived peptides
Authors: Hollenberg Morley D , Saifeddine Mahmoud
Published: April 2011

We studied the actions of receptor-activating peptide analogues (PAR4APs), modeled on the proteolytically-revealed tethered ligand sequence of murine proteinase-activated receptor-4 (PAR4), in a rat platelet aggregation assay. The PAR4APs GYPGKF-NH2 (GY-NH2) and AYPGKF-NH2 (AY-NH2) were able to cause aggregation with EC50 values of about 40 µM and 15 µM, respectively. The reverse human PAR4 sequence (VQGPYG-NH2, YG-NH2) and the PAR1AP SFLLR-NH2, did not cause aggregation. In contrast, trans-cinnamoyl-YPGKF-NH2 (tcY-NH2) did not cause aggregation but blocked aggregation caused by GY-NH2, AY-NH2, and thrombin without affecting ADP-mediated aggregation. We conclude that in contrast to the PAR1AP, the PAR4APs GY-NH2 and AY-NH2 activate rat platelets via a PAR4-related receptor and that peptide analogues modeled on the PAR4 tethered activating sequence can serve as useful agonist and antagonist probes for assessing the consequence of activating PAR4 either by PAR4APs or thrombin in rat tissue preparations.Key words: thrombin, platelets, PAR, proteinase-activated receptor-4, antagonist.
Prolactin directly stimulates transcellular active calcium transport in the duodenum of female rats
Authors: Charoenphandhu Narattaphol , Limlomwongse Liangchai , Krishnamra Nateetip
Published: April 2011

Prolactin has been postulated to be a novel calcium-regulating hormone during pregnancy and lactation. It stimulates both passive and active duodenal calcium transport in several experimental models. Our study was performed on sexually mature female Wistar rats (200250 g) to study the direct action of prolactin on calcium transport in the duodenum using the Ussing chamber technique. To evaluate the effect of prolactin on total calcium transport in the duodenum, we intraperitoneally injected rats with 0.4, 0.6, and 0.8 mg/kg prolactin. The total calcium transport was divided into voltage-dependent, solvent drag-induced, and transcellular active fluxes by applying short-circuit current and by mucosal glucose replacement with mannitol. The effect of prolactin on each flux was studied separately. Finally, to evaluate the direct action of prolactin on duodenal transcellular active flux, we directly exposed duodenal segments to prolactin that had been added to the serosal solution with or without calcium transport inhibitors. We found that 0.6 and 0.8 mg/kg prolactin ip significantly increased the total mucosatoserosa calcium flux from the control value (nmol·hr1·cm2) of 34.53 ± 6.81 to 68.07 ± 13.53 (P < 0.05) and 84.43 ± 19.72 (P < 0.01), respectively. Prolactin also enhanced the solvent drag-induced calcium flux and transcellular active calcium flux, but not the voltage-dependent calcium flux. The duodenal segments directly exposed to 200, 400, and 800 ng/mL prolactin showed a significant increase in the transcellular active calcium absorption in a dose-dependent manner, i.e., from the control value (nmol·hr1·cm2) of 2.94 ± 0.47 to 5.45 ± 0.97 (P < 0.01), 8.09 ± 0.52 (P < 0.001), and 18.42 ± 2.92 (P < 0.001), respectively. Its direct action was inhibited by mucosal exposure to 50 µM lanthanum chloride, a calcium transporter protein competitor, and serosal exposure to 0.1 mM trifluoperazine, a Ca2+-ATPase inhibitor. These studies demonstrate that the duodenum is a target organ of prolactin, which enhances transcellular active calcium transport.Key words: calcium absorption, duodenum, prolactin, solvent drag, transcellular calcium transport.
Characterization of the mechanisms involved in the gender differences inp-aminohippurate renal elimination in rats
Authors: Cerrutti Jorgelina A , Quaglia Nora B , Torres Adriana M
Published: April 2011

Gender differences in the renal handling on drugs and toxins have received too little attention. In the present study, a variety of preparations were used to examine the basis for the greater effectiveness of the male kidneys in the elimination of p-aminohippurate (PAH) in rats. Renal clearance of PAH was significantly lower in female rats as consequence of its smaller filtered and secreted load. The gender difference in the filtered load may be accounted for the lower value of glomerular filtration rate (GFR) displayed by female rats as compared with males. The lower value of the renal blood flow observed in females might explain, at least in part, the decrease in the GFR and in the secreted load of PAH. In females, maximal uptake for PAH transport into renal basolateral membrane vesicles decreased to 52 ± 9 % (P < 0.05) and Michaelis-Menten constant for PAH uptake into renal brush border membrane vesicles was increased to 163 ± 8 % (P < 0.05). These changes might also explain the lower secreted load of PAH. The sex difference in the renal clearance of PAH was also evidenced by the reduced systemic clearance observed in female rats.Key words: organic anions, transport in renal membrane vesicles, renal clearance, systemic clearance, sex.
Mechanical, biochemical, and morphological changes in the heart from chronic food-restricted rats
Authors: Okoshi Marina Politi , Okoshi Katashi , Pai Vitalino Dal , Pai-Silva Maeli Dal , Matsubara Luiz Shiguero , Cicogna Antonio Carlos
Published: April 2011

Food restriction (FR) has been shown to induce important morphological changes in rat myocardium. However, its influence on myocardial performance is not completely defined. We examined the effects of chronic FR on cardiac muscle function and morphology. Sixty-day-old WistarKyoto rats were fed a control (C) or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Fragments of the LV free wall were analysed by light microscopy, and the ultrastructure of the myocardium was examined in t...he LV papillary muscle. The myocardial collagen concentration was also evaluated. FR decreased body weight (BW) and LV weight (LVW); the LVW/BW ratio was higher in the restricted group (C, 1.86 ± 0.17 mg/g; FR, 2.19 ± 0.31 mg/g; p < 0.01). In the FR animals, the cardiac fibers were polymorphic, some of them were of small diameter and others presented lateral infoldings; the ultrastructural alterations were focal and included reduction of sarcoplasmic content, absence and (or) disorganization of myofilaments and Z line, numerous electron dense and polymorphic mitochondria, and deep infoldings of the plasma membrane. The hydroxyproline concentration was higher in the FR animals (p < 0.01). FR prolonged the contraction and relaxation time of the papillary muscle and did not change its ability to contract and shorten. In conclusion, although a 90-day period of FR caused striking myocardial ultrastructural alterations and increased the collagen concentration, it only minimally affected the mechanical function.Key words: diet, papillary muscle, undernutrition, myocardium, ultrastructure.
Peripheral administration of AT1 receptor blockers and pressor responses to central angiotensin II and sodium
Authors: Zhang Jing , Leenen Frans HH
Published: April 2011

Central administration of AT1 receptor blockers prevents salt-sensitive hypertension and inhibits progression of CHF. We investigated in Wistar rats the effectiveness of peripheral administration of two AT1 receptor blockers, losartan and embusartan, in exerting central AT1 receptor blockade. Losartan or embusartan at doses of 30 and 100 mg/kg were administered subcutaneously (sc) as a single dose, or one dose daily for 6 days. The BP responses to intracerebroventricular (icv) injection of Ang II, icv infusion of Na+-rich aCSF (0.3 M NaC1), and intravenous (iv) injection of Ang II were then measured. Losartan or embusartan at 30 and 100 mg/kg both inhibited the BP increases induced by icv Ang II and, to a lesser extent, by Na+-rich aCSF. After a single dose, this inhibition was more pronounced for losartan. However, after 6 days of treatment, there were no significant differences between the effects of losartan and embusartan. Losartan and embusartan blocked responses to Ang II iv to a similar extent. These results indicate that results from single-dose studies may not reflect the chronic steady-state, and that during chronic treatment both AT1 receptor blockers are similarly effective in inhibiting AT1 receptors in the central nervous system, when assessed by pressor responses to acute increases in CSF Na+ or CSF Ang II.Key words: AT1 receptor blockers, brain AT1 receptors, losartan, embusartan, angiotensin II, sodium.
Cooling is a potent vasodilator of deep vessels in the rat
Authors: Mustafa Seham MD , Thulesius Olav
Published: April 2011

The objectives of this study were to determine the effect of cooling on smooth muscle tone of the pulmonary artery and aorta and to clarify the basic mechanism of these responses. We recorded isometric tension in smooth muscle strips of rat pulmonary artery and aorta in organ baths during stepwise cooling. Cooling responses were tested before and after the addition of various standard agents that interfere with known neurogenic (autonomic blockers, tetrodotoxin) and myogenic mechanisms (calcium channel blockers) of relaxation. We also examined the hypothesis of the presence of a cooling-released substance. Stepwise cooling (37°C to 4°C) of aortic smooth muscle induced reproducible graded relaxations that were inversely proportional to temperature. Cooling-induced relaxation was not dependent on a neural mechanism nor the release of neurotransmitters or a cooling-released substance such as NO or CO. Cooling of pulmonary arterial and aortic smooth muscle preparations induced a graded myogenic relaxation inversely proportional to the cooling temperature. The mechanism is not dependent on local nervous or known mediators but related to a direct physico-chemical effect of cooling.Key words: cooling, vasodilatation, pulmonary artery, aorta.
Effect of antidepressants on ATP-dependent calcium uptake by neuronal endoplasmic reticulum
Authors: Couture L , Élie R , Lavoie P -A
Published: April 2011

This study investigated the effect of tricyclic and atypical antidepressants on adenosine triphosphate (ATP) dependent calcium uptake by the endoplasmic reticulum of lysed synaptosomes from rat brain cortex. Tricyclic antidepressants (imipramine, desipramine, clomipramine, amitriptyline) exhibited no effect in the lower range (0.06 to 2 µM) of drug concentrations, and a concentration-dependent inhibition of calcium uptake in the upper range (6 to 200 µM). A concentration-dependent inhibition was observed for atypical antidepressants (mianserin, desmethylmianserin, venlafaxine, desmethylvenlafaxine, fluoxetine) in both the lower and the upper range of drug concentrations. Since no stimulation of calcium uptake was observed in either concentration range, it appears that the tricyclic and atypical antidepressants tested are not capable of normalizing, through their effect on the endoplasmic reticulum, an overactive calcium signal, which is possibly implicated in the etiology of affective disorders. Also, although only marginal inhibition of calcium uptake is expected at brain concentrations of tricyclics and mianserindesmethylmianserin that are likely to be encountered during clinical use, a more substantial inhibition could occur with fluoxetine.Key words: adenosine triphosphate-dependent calcium uptake, neuronal endoplasmic reticulum, lysed brain synaptosomes, tricyclic antidepressants, atypical antidepressants.
Ammonium ion enhances the calcium-dependent gating of a mammalian large conductance, calcium-sensitive K+ channel
Authors: Braun Andrew P
Published: April 2011

We observed that the current amplitude and activation of expressed, mouse brain large conductance, calcium-sensitive K+ channels (BKCa channels) may be reversibly enhanced following addition of low concentrations of the weakly permeant cation NH4+ to the cytoplasmic face of the channel in excised, inside-out membrane patches from HEK 293 cells. Conductance-voltage relations were left-shifted along the voltage axis by addition of NH4Cl in a concentration-dependent manner, with an EC50 of 18.5 mM. Furthermore, this effect was observed in the presence of cytosolic free calcium (~1 µM), but was absent in a cytosolic bath solution containing nominally zero free calcium (e.g., 5 mM EGTA only), a condition under which these channels undergo largely voltage-dependent gating. Recordings of single BKCa channel events indicated that NH4+ increased the channel open probability of single channel activity ~3-fold, but did not alter the amplitude of single channel currents. These findings suggest that the calcium-sensitive gating of mammalian BKCa channels may be modified by other ions present in cytosolic solution.Key words: potassium channel, calcium, modulation, electrophysiology.
Role of IK and If in the pacemaker mechanisms of sino-atrial node myocytes
Authors: Zhang Hengtao , Vassalle Mario
Published: April 2011

The role of IK (delayed rectifier current) and If (hyperpolarization-activated current) in dominant and subsidiary pacemaker ranges was studied in single myocytes isolated from the guinea pig sino-atrial node by means of a perforated patch-clamp technique. In the dominant pacemaker range (approx. 55 to 40 mV), IK tails are present whereas If is not activated. In the subsidiary pacemaker range (approx. 80 to 70 mV), If is large whereas IK is minimal and reversing. The threshold for If activation is more negative at short time intervals. Larger or longer depolarizations to 40 mV and +20 mV deactivate If more and are followed by faster reactivation of If. Steps of 200300 ms duration to +20 mV completely deactivate If. The slope conductance decreases during depolarizations at 40 and +20 mV and quickly re-increases after the steps. The If deactivation range is between 70 and +10 mV, with a V1/2 of 35 mV. Depolarizations from 80 to +20 mV at a rate of 120/min limit the subsequent If reactivation owing to the short diastole. We conclude that IK plays a predominant role in the dominant pacemaker range and If does so in the subsidiary pacemaker range. Either pacemaker mechanism is used by sino-atrial node cells depending on the diastolic potential range. A previous depolarization markedly increases the amplitude and rate of If reactivation.Key words: dominant and subsidiary pacemaker ranges, sinus discharge and dual pacemaker mechanisms, delayed rectifier current IK, hyperpolarization-activated current If, factors regulating If, pacemaker shifts.
The nitric oxide–cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine
Authors: Ozdemir Ercan , Bagcivan Ihsan , Durmus Nedim , Altun Ahmet , Gursoy Sinan
Published: April 2011

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180–210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), NG-nitro-l-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide–cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.
CARDIOVASCULAR EFFECTS OF THE INSECTICIDE ENDRIN
Authors: Emerson Jr. T. E. , Brake C. M. , Hinshaw L. B.
Published: April 2011

Little is known of the cardiovascular effects of endrin insecticide. Experiments to investigate these phenomena were carried out on dogs with a variety of preparations. Results show that acute administration of endrin produces bradycardia, hypertension, copious salivation, hyperexcitability, tonic–cionic convulsions, increased body temperature, leukocytosis, hemoconcentration, and decreased blood pH. Cerebral venous pressure and cerebrospinal fluid pressure elevations are also prominent features of endrin poisoning. Although most of these effects appear to be caused by endrin acting directly on the central nervous system some may result secondarily from altered cerebral hemodynamics.
THE ROLE OF LACTATE IN THE STIMULATION OF THE OXYGEN CONSUMPTION OF FROG MUSCLE BY INSULIN
Authors: Gourley D. R. H. , Fisher Kenneth C.
Published: April 2011

Lactate, citrate, succinate, or acetate added to isolated muscles suspended in Ringer solution in a Warburg flask produced an increase in the rate of oxygen consumption by the muscles. At a given molar concentration of these substances the increase was greatest with lactate and was progressively less with the addenda in the order given. When the concentration of each substance was adjusted so that the rate of oxygen consumption was the same with all of them, the addition of insulin produced an increase in the oxygen uptake which was of the same magnitude in each case. Evidence is presented which suggests that by causing spontaneous activity in the muscle, the acetate, succinate, and citrate may bring about a production of lactate.The extra oxygen consumed upon the addition of lactate could account for the complete oxidation of only a small part of the lactate which actually disappeared in an experiment. By assuming that all of this extra oxygen was used in the complete oxidation of lactate, it was calculated from the total lactate utilization in the presence or absence of insulin that the major effect of insulin was on the fraction of utilized lactate which was oxidized. This conclusion was also suggested by experiments with monoiodoacetate.
A NEW TECHNIQUE FOR TIDAL VOLUME MEASUREMENT IN UNANAESTHETIZED SMALL ANIMALS
Authors: Leong K. J. , Dowd G. F. , Macfarland H. N.
Published: April 2011

An open-circuit, valveless, continuous airflow respirographic technique has been developed for measuring the tidal volume, minute volume, respiratory rate, and respiratory airflow pattern simultaneously and continuously. Several electronic devices have been designed to provide the resolving power which is necessary for this measuring system. Results show that the instrument is capable of recording the pulse contour up to a frequency of 40 cycles per second and the system applies no measurable loading to the airstream. Consequently, the various respiratory parameters can be measured accurately. The tidal volumes of unanaesthetized young adult rats (100–300 g) tested under our experimental conditions were found to vary as the 0.67 power of the body weight.
EFFECT OF METHYLPHENIDATE ON SPONTANEOUS ACTIVITY, FOOD INTAKE, AND COLD TOLERANCE OF PROPYLTHIOURACIL-TREATED RATS
Authors: Fregly Melvin J. , Black Bruce A.
Published: April 2011

Dietary administration of methylphenidate to rats increases locomotor activity (tilt cage method) roughly in proportion to the logarithm of the dose ingested. The results suggest that a dose of 62 mg methylphenidate/kg body wt. per day increases activity level by 50%. At higher dose levels, a tolerance appears to develop and is characterized by high initial levels of activity (days 1 to 3) followed by reduction of activity to a new stable level (days 4 to 6). Methylphenidate increases activity level and decreases food intake and body weight of both hypothyroid (propylthiouracil-treated) and control rats subjected to ambient temperatures of 10, 15, 20, and 28 °C. It fails to increase the tolerance of hypothyroid rats either to chronic (10 and 15 °C) or to acute (5 °C) cold exposure.
EXCRETION OF INJECTED CATECHOL AMINES BY WHITE RATS AT 23 °C AND 2 °C
Authors: Smith Lorraine C. , Dugal L.-P.
Published: April 2011

On the average 2.8% of an injected dose of adrenaline and 2.5% of an injected dose of noradrenaline were excreted unchanged in the urine of white rats kept at 23 °C. For rats kept at 2 °C these values were increased to 4.2% for adrenaline and 4.4% for noradrenaline. The amount of naturally produced catechol amines excreted by rats in the cold was considerably larger than the amount excreted by rats at room temperature. It is suggested that the receptor sites are more nearly saturated in the cold. Thus inactivation of an injected catechol amine would be less complete and a larger percentage would be excreted in the urine.
CHANGES IN THE MULTIPLE HEMOGLOBIN PATTERNS OF SOME PACIFIC SALMON, GENUS ONCORHYNCHUS, DURING THE PARR–SMOLT TRANSFORMATION
Authors: Vanstone W. E. , Roberts Eve , Tsuyuki H.
Published: April 2011

By employing starch gel electrophoresis it has been found that coho salmon fry and smolts contain 10 anodal-migrating, and 12 cathodal-migrating, hemoglobin fractions. Prepuberal [Formula: see text]-year-old coho salmon caught at sea and sexually mature adults taken from fresh water contained the same anodal fractions and at approximately the same concentrations as were found in fry and smolts. However, the concentrations of the cathodal fractions had increased so that these were very nearly equal to those of the anodal fractions. Similar hemoglobin changes were found in both anadromous and land-locked sockeye salmon, but in this species seven anodal and six cathodal fractions were present at their "adult" concentrations in fry and smolts. Six other cathodal fractions which were absent entirely or present only in trace amounts in fry and smolts increased to their adult concentrations some time later in the life cycle of both varieties of sockeye. It is postulated that these changes reflect an ecological adaption to life in the ocean.
ON THE MECHANISM WHEREBY CERTAIN NUCLEOTIDES PRODUCE CONTRACTIONS OF SMOOTH MUSCLE
Authors: Daniel E. E. , Irwin John
Published: April 2011

The mechanism of the contractile actions of adenine nucleotides on rat uterine muscle has been analyzed. ATP and ADP were about equally effective in causing contraction and much more effective than AMP and adenosine. Orthophosphate and pyrophosphate were less effective. None of the nucleotides caused inhibition of contraction to other drugs such as acetylcholine. Neither selective inhibition of known receptors nor depolarization by K2SO4 prevented these contractions, but calcium depletion sufficient to prevent acetylcholine contractions prevented ATP and ADP contractions. Metabolic inhibitors also produced parallel depression of responses to acetylcholine and the nucleotides.The possibility was entertained that these nucleotides might have acted by virtue of their ability to complex magnesium present in the cell membrane, thereby favoring calcium entry and contraction; hence a variety of experiments were done to test this hypothesis. Concentrations of calcium and magnesium, either when the cations were free in the bath solution or when they were complexed with ATP, were varied and the effects on contraction noted. The results were consistent with the hypothesis. Substitution of strontium for calcium enhanced the effectiveness of ATP in evoking contractions.
STUDIES OF ESTERASES AND MULTIPLE FORMS OF CHOLINESTERASE IN EQUINE PLASMA
Authors: Oki Y. , Oliver W. T. , Funnell H. S.
Published: April 2011

The esterases of horse and donkey plasma were separated by starch-gel electrophoresis and their characteristics determined using various substrates, inhibitors, and activators. Four zones of cholinesterase activity were present in all samples examined. One of these zones, C4, always predominated; another zone, C5, a variant form, appears to be genetically controlled. Zone B, an aliesterase hydrolyzing short- and long-chain fatty acid esters, was present in all horse plasma, but not in donkey plasma. Zone D, a type of aliesterase utilizing short-chain fatty acid esters, was found only in the draft horse breeds. Both horse and donkey plasma contained two components of zone A2, an arylesterase, one being of lesser activity. Zone A1, which had arylesterase-like activity, probably corresponds to ''albumin esterase" of human plasma.
THE EFFECT OF AGE ON THE ELASTICITY OF THE MAJOR BRAIN ARTERIES
Authors: Busby Douglas E. , Burton Alan C.
Published: April 2011

In previous work on peripheral arteries the law of Laplace has been applied to the pressure–volume data to yield the elastic constants and interrelation of function of elastin and collagenous fibers in the wall, and the changes with age. Similar analysis of major brain arteries has been made on autopsy specimens, aged 2 to 90. Volume (micrometer syringe) and pressure (electromanometer) in arterial segments were accurately measured. Absolute volumes were obtained by collapsing the artery with negative pressure, and the "unstretched circumferences" of the vessel were deduced from the curves. Tension–circumference curves were constructed. These showed the characteristic increasing slope (increased "elastance" or "stiffness") with increasing degree of stretch, interpreted as successive "recruitment" of collagen fibers as they reach their unstretched length.Increases in arterial length with distension were very small and negligible in vessels older than 30 years. Maximum slope (stiffness) was reached at pressures in the physiological range. The maximal stretch was 26 to 38% for vessels aged 30 to 90 years. This is less than for peripheral arteries, except those over 80 years old.Ageing showed itself mainly in reduction of the stretch required to bring 50% of the collagen fibers to their unstretched length, i.e. in the "degree of slackness". This was 30% stretch for younger vessels, 20% for the older. Unlike the peripheral arteries, the brain arteries show no significant increase with age in the maximal stiffness (related to their total collagen content). The mean value of the Young's modulus of the wall at high pressures was 1.93 ± 0.67 × 107 dynes/sq.cm. No significant change in thickness of the wall or lumen diameter with age was found.It is concluded that the major brain arteries are less distensible than peripheral arteries of comparable diameter, particularly in youth. Distensibility decreases with age, mainly because the "degree of slackness" of the collagen fibers is reduced. At physiological pressures the major resistance to distension is due to the collagen fibers rather than to the elastin fibers, which appear histologically to be less abundant, except in the elastica interna, than in peripheral arteries.
ISOZYMES OF SERUM CHOLINESTERASE: A NEW POLYMERIZATION SEQUENCE
Authors: LaMotta Rudolph V. , McComb Robert B. , Wetstone Howard J.
Published: April 2011

The isozymes of serum cholinesterase are shown to be interconvertible. Concentration of the individual isozymes results in an electrophoretically slower functional enzyme unit, whereas dilute solutions result in functional units with greater mobility. Since each of the four most mobile isozymes when isolated is convertible to the major isozyme form and each slower isozyme when isolated can be converted into the more mobile forms, this sequence is most likely stepwise in nature. The results indicate that the isozymes of serum cholinesterase are a manifestation of a polymerization sequence.
NUMBER OF OSTEOBLASTS PER UNIT AREA OF OSTEOID SEAM IN CORTICAL HUMAN BONE
Authors: Schen S. , Villanueva A. R. , Frost H. M.
Published: April 2011

The fifth, sixth, or seventh ribs from 97 metabolically normal people of all ages were examined. Mineralized longitudinal sections were specially stained to show both osteoid seams and osteoblasts. In 19 persons, the mean number of osteoblasts per mm2 of active osteoid seam surface on 111 seams was 4500. In 66 persons, a layer of osteoblasts was present on only 29% of 121 seams. The seams without layers of osteoblasts nevertheless were part of actively forming Haversian systems as judged by other criteria. No significant age differences were observed in either value.
ACTION OF ETHER ON FROG SKELETAL MUSCLE
Authors: Inoue F. , Frank G. B.
Published: April 2011

The mechanisms for the excitability changes produced by ether on the electrical activity of frog skeletal muscle were investigated by intracellular microelectrode techniques. Low concentrations of ether (less than 1%) increased excitability by increasing the 'effective resistance' between the inside and the outside of the fiber at the point of stimulation, thereby reducing the current needed to initiate an action potential. Higher concentrations decreased excitability by inhibiting the specific increase in sodium conductance which normally follows an adequate stimulus and is responsible for the rising phase of the action potential.
IDENTIFICATION OF PHARMACOLOGICALLY ACTIVE SUBSTANCES IN THE INDIAN STINGING NETTLE, URTICA PARVIFLORA (ROXB.)
Authors: Saxena P. R. , Pant M. C. , Kishor K. , Bhargava K. P.
Published: April 2011

The presence of histamine, 5-hydroxytryptamine (5-HT), and acetylcholine has been demonstrated in the Indian stinging nettle, Urtica parviflora (Roxb.). In addition, the presence of a histamine-liberating substance is strongly indicated. The whole leaves of the plant were extracted in acetone. The acetone-extracted material was used to detect 5-HT and acetylcholine. The acid-treated extract was used for the detection of histamine, and the histaminase-treated extract was used for the detection of the histamine liberator. Appropriate biological and chromatographic tests were performed for the pharmacologically active constituents.
NUTRITIONAL STRESS AND THE ACUTE-PHASE REACTANTS OF RAT SERUM IN EXPERIMENTAL INFLAMMATION
Authors: Weimer Henry E. , Godfrey James F.
Published: April 2011

The effects of acute starvation, food restriction, and protein depletion on the response of serum proteins to turpentine-induced inflammation were investigated in adult, male, Sprague–Dawley rats. The animals were fed nutritionally inadequate diets until a 20% weight loss was attained, then they were challenged. Significant increases occurred in the concentrations of protein-bound hexose, protein-bound hexosamine, and protein-bound sialic acid, and in the fibrinogen, seromucoid, α2- and β-globulin fractions; a new protein, α2-AP (acute-phase) globulin, appeared in the serum concomitant with decreased levels of total protein, albumin, and γ-globulin after the injection of the phlogogenic agent. The same pattern of response to inflammation occurred, irrespective of whether the rats were fed the stock or experimental diets.The conclusion was drawn that the response of the acute-phase reactants of rat serum to tissue injury is of such magnitude that it is not suppressed by several types of severe nutritional stress. Possible factors involved in the response are discussed.
FATTY ACID COMPOSITION OF HEART PHOSPHOLIPIDS IN THE AORTA-LIGATURE CARDIOPATHY
Authors: Prioreschi P. , Kuksis A. , Rogers B.
Published: April 2011

Total cardiac lipids, phospholipids, and the gas-chromatographic pattern of the fatty acids of the various phospholipid fractions separated on thin-layer chromatography were studied before the development of the aorta-ligature cardiac necroses in the rat. The most significant changes were found in the cardiolipin fraction of the treated animals. In this fraction, 24 hours after the ligature of the aorta, there was a relative decrease of C18:2 and increase of two components tentatively identified as long-chain unsaturated fatty acids. Changes in the fatty acid composition of other phospholipids were not considered significant.
THE MEASUREMENT OF BLOOD PRESSURE, THE CRITICAL OPENING PRESSURE, AND THE CRITICAL CLOSING PRESSURE OF DIGITAL VESSELS UNDER VARIOUS CIRCUMSTANCES
Authors: Gaskell Peter
Published: April 2011

A spectroscopic technique for the estimation of the critical opening pressure (COP) or critical closing pressure (CCP) of small vessels in the finger is described. The spectroscopic method of estimation of the systolic blood pressure, which is part of the technique and which involves the detection of reappearance of oxyhemoglobin absorption bands in the spectrum of reflected light from the skin distal to a blood pressure cuff that is slowly deflated, was compared to the auscultatory technique in 38 subjects on 53 occasions and gave the same results. The COP of small vessels in the finger estimated by the spectroscopic technique was decreased by body heating and by digital nerve block as had been previously shown by the microscopical method. The COP of vessels in the finger after digital nerve block in 43 normotensive young women between the ages of 18 and 22 years ranged from 2 to 19 mm Hg with a mean of 9.5 ± 4.6 (S.D.) mm Hg. When the COP was estimated in many of the same subjects after preparation as for measurement of the basal metabolic rate, in most cases it fell within the range of values obtained after nerve block. The COP in 26 subjects ranged from 1 to 22 mm Hg with a mean of 10.9 ± 5.0 (S.D.). The values for CCP estimated by the spectroscopic method in 81 individuals were not significantly different from those for COP estimated on the same occasion.
THE EFFECT OF FUROSEMIDE, A NEW DIURETIC AGENT, ON RENAL CONCENTRATING AND DILUTING MECHANISMS
Authors: Morrin Peter A. F.
Published: April 2011

The effect of a new diuretic, Furosemide, has been studied in normal subjects undergoing both osmotic and water diuresis. A marked increase in the excretion of sodium and water was observed, the latter amounting to 30% of the glomerular filtrate. In the hydropenic subjects the drug virtually abolished negative free water clearance, which indicates that the site of action is in the ascending limb of Henle's loop. In the water-loaded subjects, free water clearance was decreased but not abolished, which suggests that urinary dilution distal to the ascending limb of Henle's loop is not significantly impaired by the diuretic.
EFFECTS OF CHRONIC INTAKE OF ETHANOL ON RATE OF ETHANOL METABOLISM
Authors: Hawkins Rosemary D. , Kalant H. , Khanna J. M.
Published: April 2011

In two separate studies of 6 and 12 weeks duration, adult male rats of the Wistar strain received ethanol in a total daily dose of about 9 g/kg. Growth rate was the same as that of glucose-treated controls. In comparison with controls of comparable weight, ethanol-treated rats showed significant increases in liver alcohol dehydrogenase (LAD) activity at all times after the first 2 weeks, but no significant change in catalase activity. The rate of disappearance of ethanol from the blood after a test dose was also significantly increased in the chronically treated rats, and the increase was initially comparable to that found in LAD activity. Later, the rate of ethanol disappearance rose more than could be explained by increased LAD activity. Normal male rats showed higher liver catalase activity than did normal females, but did not differ in LAD activity, which was higher at 9–10 weeks of age than in older or younger animals. It is suggested that failure of some investigators to find an alcohol-induced increase in LAD activity may be due to different responses by males and females.
THE BEHAVIOR OF ATRIO–VENTRICULAR NODAL RHYTHM FOLLOWING DIRECT PERFUSION OF THE SINUS NODE
Authors: Nadeau R. A. , James T. N.
Published: April 2011

Direct perfusion of the canine sinus node with various pharmacological agents having negative chronotropic effects commonly leads either to abrupt sinus arrest or to a gradual transition from sinus to atrio–ventricular (A–V) nodal rhythm with progressive shortening of the P–R interval. The reappearance of sinus rhythm is usually preceded by a change in A–V nodal rate and a progressive lengthening of the P–R interval to a stable value. During A–V nodal rhythm, changes in heart rate are observed following injections into the sinus node artery. As perfusion of the sinus node is selective, these cannot be attributed to a direct pharmacological effect of the perfusates on the A–V node. Deliberate suppression of A–V nodal pacemaking dominance reveals the persistence of slow sinus node activity which is unapparent electrocardiographically during A–V nodal rhythm. It would seem that even in the absence of P waves, the sinus node may still influence the rate of the A–V node. These observations are consistent with the hypothesis that the sinus and A–V nodes behave as a system of coupled relaxation oscillators.
ELECTRICAL AND CONTRACTILE RESPONSES OF THE PYLORIC REGION TO ADRENERGIC AND CHOLINERGIC DRUGS
Authors: Daniel E. E.
Published: April 2011

Two kinds of electrical activity can be recorded in the pyloric antrum with extracellular electrodes: an initial triphasic spike-like potential and sometimes a second potential. Contractions of the antrum were accompanied by the second (negative) potential wave. The initial potential was propagated. An initial potential preceded each second potential during contractile activity and appeared to initiate it. These patterns of electrical activity were compared with those in the duodenum previously reported. Cholinergic stimulants (acetylcholine, methacholine, carbamylcholine, and nicotine) infused intra-arterially in threshold amounts (0.1 to 1 μg) produced in the antrum a premature initial wave, one or more second potentials with contractions, or both effects. The nature of the response depended upon the timing of the infusion in relation to the initial wave and the dose of drug used. Premature initial waves were capable of antiperistaltic conduction. Doses of acetylcholine higher than threshold caused both premature initial waves and a series of second potentials. Excessive doses (>1 μg) caused disruption of initial waves. Both muscarinic and nicotinic cholinergic receptors were identified.Catecholamines infused intra-arterially in threshold amounts temporarily obliterated second potentials and associated contractions in the antrum. Pharmacological analysis suggests that alpha receptors were involved. Beta inhibitory receptors were also present. Higher concentrations of catecholamines, or atropine, may produce a series of rapid initial waves without second potentials or contractions, which have been designated the "sympathetic dominance pattern". Production of this pattern by catecholamines probably resulted from actions on alpha receptors. Noradrenaline and adrenaline suppress fast spike potentials and contractions in the duodenal bulb. In larger amounts they decrease slow-amplitude potentials and increase their frequency. Isopropylnoradrenaline in most experiments caused contractions and fast spike potentials in the duodenal bulb when given in small or moderate amounts. The inhibitory effects of catecholamines were on alpha receptors, but beta receptors with excitatory effects may also be present.