bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROLE OF MESANGIAL CELLS IN MACULA DENSA TO AFFERENT ARTERIOLE INFORMATION TRANSFER
Authors: Goligorsky Michael S. , Iijima Kazumoto , Krivenko Yuri , Tsukahara Hirokazu , Hu Yu , Moore Leon C. 
Published: June 2007

SUMMARY1. Extraglomerular mesangial cells are strategically positioned between the macula densa and the afferent arteriole. These cells form a syncytium and are connected with glomerular mesangial cells via gap junctions. The model of immunoablation of mesangial cells in anti‐Thy‐1 glomerulonephritis carries the promise for understanding the function of mesangial cells as potential transmitters of information between the macula densa and the afferent arteriole.2. The above anatomical relations between structures in the juxtaglomerular apparatus predict several possible routes of information flow. This review charts some hypothetical routes.3. Research into the messenger systems involved in the transfer of signals from the macula densa to mesangial cells and from mesangial cells to the afferent arteriole suggests several candidate molecules to function in this capacity. Mechanisms of action for each candidate are discussed.4. The oscillating nature of the afferent signal and efferent function in the tubuloglomerular feedback system, as well as other discoveries, offer a fertile field for future studies.
EFFECTS OF 5HT2 RECEPTOR ANTAGONISTS ON RESPONSES TO POTASSIUM DEPOLARIZATION IN RAT ISOLATED AORTA
Authors: Okoro EO , Marwood JF 
Published: June 2007

SUMMARY1. In order to determine whether 5HT2 receptor antagonists can modify Ca2+ uptake via voltage‐operated Ca2+ channel (VOC) in arterial smooth muscle, a comparative study of the effects of selected Ca2+ uptake blockers and 5HT2 receptor antagonists on K+‐induced contractions of rat aortic strip was undertaken.2. The antagonist drugs studied included the Ca2+ uptake blockers verapamil, nifedipine, felodipine, diltiazem and cin‐narizine, the 5HT2 receptor antagonists cyproheptadine, ritanserin, mianserin, and ketanserin and the α1‐adrenoceptor antagonist prazosin.3. With the notable exception of prazosin, each of these compounds diminished K+‐induced aortic responses.4. The following order of potencies (mean IC50 values in mol/L) was established: felodipine (7.0 × 10‐11) >nifedipine (4.8 × 10‐9) >verapamil (5.5 × 10‐8) >cyproheptadine (6.2 × 10‐8) > diltiazem (4.1 × 10‐7) >cinnarizine (1.3 × 10‐6) >ritanserin (1.8 × 10‐6) >ketanserin (9.0 × 10‐6) > mianserin (2.0 × 10‐5).5. The results suggest that antagonists of 5HT2 receptors can modulate Ca2+ uptake via VOC in rat aorta.
RENAL EFFECTS OF RILMENIDINE IN VOLUME‐LOADED ANAESTHETIZED DOGS
Authors: Evans Roger G. , Shweta Amany , Malpas Simon C. , Fitzgerald Sharyn M. , Anderson Warwick P. 
Published: June 2007

SUMMARY1. In anaesthetized, fluid expanded rats rilmenidine has diuretic and natriuretic effects. There is strong evidence that the natriuresis is mediated by putative imidazoline receptors. In contrast, in conscious euvolaemic dogs rilmenidine has a diuretic effect that is entirely attributable to activation of a2‐adrenoceptors, but no natriuretic effect. To determine whether the effects of rilmenidine are truly species dependent, or merely dependent upon the influences of anaesthesia and volume status, we tested the effects of rilmenidine in pentobarbitone anaesthetized, volume‐loaded dogs.2. The effects of rilmenidine in anaesthetized, volume‐loaded dogs were similar to those found in conscious euvolaemic dogs. Compared with vehicle treatment, levels of glomerular filtration rate, urine flow and haematocrit were increased following rilmenidine treatment. No effect of rilmenidine on sodium excretion was observed.3. We conclude that the renal responses to rilmenidine in dogs are largely unaffected by anaesthesia and plasma volume status. In particular, the natriuretic effect seen in rats was not observed. We conclude that putative imidazoline receptors do not have a major influence on sodium excretion in dogs.
BLOOD PRESSURE REGULATION IN BARORECEPTOR‐DENERVATED RATS
Authors: Sved Alan F. , Schreihofer Ann M. , Jr Curtis K Kost 
Published: June 2007

Key words1. Arterial baroreceptor denervation produces acute hypertension, but chronically denervated animals have an average arterial pressure that is similar to that of baroreceptor intact animals.2. Although cardiopulmonary baroreceptors and renal compensations have been suggested to mediate the restoration of a normal average arterial pressure in sino‐aortic denervated rats, such mechanisms are inconsistent with the available data.3. At present the processes involved in the restoration and long‐term maintenance of a normal average arterial pressure in chronic baroreceptor denervated animals are not known. An understanding of the regulation of arterial pressure that occurs in the absence of arterial baroreceptor reflexes may provide important new insights into the mechanisms underlying the long‐term regulation of arterial pressure.
ACTIONS OF ANGIOTENSIN IN THE SUBFORNICAL ORGAN AND AREA POSTREMA: IMPLICATIONS FOR LONG TERM CONTROL OF AUTONOMIC OUTPUT
Authors: Ferguson Alastair V. , Bains Jaideep S. 
Published: June 2007

SUMMARY1. Considerable physiological and anatomical evidence indicates that circulating angiotensin II (AngII), plays important roles in the long‐term regulation of autonomic output as a result of actions in two circumventricular structures, the subfornical organ (SFO) and area postrema (AP).2. Extracellular recordings have demonstrated excitatory actions of AngII on neurons from both of these structures which are ATi receptor mediated, maintained when cells are placed in synaptic isolation, and are dose dependent. Interestingly SFO neurons appear to be an order of magnitude more sensitive to AngII than those in AP.3. Recent calcium imaging studies have demonstrated that AngII induces increases in intracellular calcium in both SFO and AP neurons. Whole cell patch recordings have also begun to provide important information suggesting that AngII actions may modulate voltage activated ion channels in these two structures to elicit its observed actions on circumventricular organs (CVO) neurons at the blood‐brain interface.4. Through these actions circulating AngII is thus able to influence efferent projections from these CVO which in turn influence the output of hypothalamic cells projecting to the posterior pituitary (vasopressin secretion), nucleus tractus soli‐tarius (NTS), and intermediolateral cell column of the spinal cord (to influence sympathetic preganglionics), and medullary neurons in the NTS.
EFFECTS OF ALBUMIN ON THE DISPOSITION OF MORPHINE AND MORPHINE‐3‐GLUCURONIDE IN THE RAT ISOLATED PERFUSED LIVER
Authors: O'Brien Josephine A. , Evans Allan M. , Nation Roger L. 
Published: June 2007

SUMMARY1. The effect of albumin on the disposition of morphine and hepatically generated morphine‐3‐glucuronide (M3G) was investigated in the single‐pass rat isolated perfused liver.1. Interest in the pharmacokinetic and pharmacodynamic properties of the enantiomers of chiral drugs has greatly increased in recent years. This is particularly so for agents used in anaesthesia.2. Chiral compounds are those that can exist in two non‐superimposable forms. Each form is termed an enantiomer or stereoisomer. Two naming systems are in use: one uses the terms (+) and (–) to indicate the direction the compound will rotate polarized light, while the other system, based on the absolute three‐dimensional structure of the enantiomers, uses the terms R and S.3. Investigation of the stereoisomers of the volatile anaesthetic agent isoflurane is increasing our understanding of the mechanism of general anaesthesia. Current evidence suggests a protein, rather than a lipid, receptor site.4. Investigation of the stereoisomers of local anaesthetics is increasing the safety of these drugs.5. For bupivacaine, a widely used amide local anaesthetic, important enantiomeric differences can be found for toxicity, clinical effect and pharmacokinetics. In particular S‐(–)‐bupivacaine has an improved central nervous system and cardiac safety profile. This is partly explained by the pharmacokinetic differences.6. Based on these differences, ropivacaine, a propyl homo‐logue of bupivacaine, has been produced solely as the S‐(–)‐enantiomer. The available evidence suggests significantly improved safety for this agent over racemic bupivacaine.
INTERACTIONS OF Na+, H2O2 AND THE Na+‐Ca2+ EXCHANGER STIMULATE Ca2+ RELEASE IN CK1.4 CELLS
Authors: Fang Yan , Rong Mingyang , He Lianfang 
Published: June 2007

SUMMARY1. The present study aimed to demonstrate that interactions of cations, hydrogen peroxide (H2O2) and the Na+‐Ca2+exchanger stimulate Ca2+ release and oscillations of cytosolic Ca2+ [Ca2+]i in non‐transfected Chinese Hamster Ovary (CHO) C1 cells and in transfected CHO (CK1.4) cells that contained an expression vector coding the Na+‐Ca2+ exchanger sequence.2. The [45Ca2+] uptake assay, fura‐2 fluorescence imaging and 22 and 23 factorial orthogonal statistics provide comparative, direct, efficient, quantitative and transient methods to delineate the effects of such interactions on Ca2+ influx, Ca2+release and [Ca2+]i in C1 and CK1.4 cells.3. In contrast to the control of either Na+‐, Ca2+‐ or H2O2‐free or CI cells, an elevated [45Ca2+] uptake was induced by Ca2+, Na+ and H2O2 individually and in combination, intracellular Ca2+ release was activated by H2O2 and by combinations of either H2O2 and Na+, H2O2 and the Na+‐Ca2+ exchanger, Na+ and the Na+‐Ca2+ exchanger or by H2O2, Na+ and the Na+‐Ca2+ exchanger and a rise in [Ca2+]i was triggered by H2O2, Na+ and a combination of Na+ and the Na+‐Ca2+exchanger.4. These results indicate that interactions between H2O2, Na+ and the Na+‐Ca2+ exchanger stimulate intracellular Ca2+mobilization via Ca2+‐induced Ca2+ release mechanisms, ATP‐activated G‐protein coupled P2y‐purinoceptor‐sensitive pathways, Na+‐Ca2+ exchanger‐mediated Ca2+ influx and cation‐π interaction (a strong non‐covalent force between the cation and the π face of an aromatic structure in the transmembrane protein).5. The present findings provide important clues for understanding Ca2+ signal transduction mechanisms from the plasma membrane to the endoplasmic reticulum.
EFFECT OF BLOOD FLOW AND HAEMATOCRIT ON THE RELATIONSHIP BETWEEN MUSCLE VENOUS Po2 AND OXYGEN UPTAKE IN DOG MAXIMALLY CONTRACTING GASTROCNEMIUS IN SITU
Authors: Kohzuki H. , Enoki Y. , Ohga Y. , Sakata S. , Shimizu S. , Morimoto T. , Kishi T. , Takaki M. 
Published: June 2007

SUMMARY1. To clarify the limiting factors for peak V̇o2 (V̇o2peak)> we measured muscle venous Po2 (Pvo2) and V̇o2, peak under various O2 delivery conditions (arterial O2 concentration X flow) via the alteration of blood flow and haematocrit (Hct) in anaesthetized dog gastrocnemius muscle (n= 11) stimulated by 1 Hz isometrically and tetanically.2. Two levels of flow (high and moderate) were maintained by using a pump (ISO and 100 mL/min per 100 g, respectively). Haematocrit was adjusted to 45 and 30% by isovolaemic haemodilution with dextran (MW 40 000).3. The decrease in Hct induced a 31% decrease in O2 delivery (P<0.05), a 9–12% decrease in Pvo2, a 23% decrease in V̇o2, peak(P<0.05) and a 12–14% increase in O2 extraction (V̇o2/O2delivery) at both flow levels. The decrease in flow induced a 24–25% decrease in O2 delivery (P<0.05), a 15–17% decrease in Pvo2 (P<0.05), a 9% decrease in V̇o2,peak (P<0.05) and a 19–22% increase in O2 extraction (P<0.05) at both Hct levels.4. The results suggest that the limiting factor of V̇o2peak, unrelated to O2 diffusion limitation (i.e. the change in the heterogeneity of V̇o2 to O2 delivery ratio among capillaries), due to lowering Hct may be different from that due to lowering blood flow in maximally contracting muscle.
STRUCTURE AND FUNCTION OF THE ADVENTITIAL AND MUCOSAL NERVE PLEXUSES OF THE BRONCHIAL TREE IN THE DEVELOPING LUNG
Authors: Sparrow MP , Weichselbaum M. 
Published: June 2007

SUMMARY1. The aim of the present study was first to determine when airway smooth muscle first appears in the airways of the developing foetal lung and when its contractility is mature and, second, when the airway smooth muscle becomes innervated, both structurally and functionally.2. Narrowing and relaxation of the airways of the intact bronchial tree from the lungs of foetal pigs at varying stages of gestation was recorded by real time video microscopy. Nerves and smooth muscle were stained immunohistochemically and their spatial relationships were visualized by confocal microscopy.3. From early in gestation (pseudoglandular stage/branching morphogenesis), airways were covered with a single layer of smooth muscle cells orientated cylindrically around the airway wall. Thick nerve trunks containing loosely packed nerves, with ganglia forming at their junctions ensheathed the airways to the growing tips, with a network of fine varicosed nerves lying on the smooth muscle cells. Some of these nerves were functional and cholinergic, as electrical field stimulation caused substantial narrowing that was blocked by atropine and by tetrodotoxin. By mid‐term, an extensive plexus of nerves, well‐defined ganglia and varicosed nerves to the smooth muscle had developed. Some nerves extended through the airway smooth muscle to form the elements of a mucosal nerve plexus in conjunction with developing vascular tissue forming a bronchial circulation. In 3 week postnatal pigs the distal and terminal airways were densely supplied with varicosed nerves to the smooth muscle. The ganglia were more centrally located.4. An abundant network of calcitonin gene‐related peptide (CGRP) nerves with prominent nerve endings lay just below the surface of the epithelium. The nerve bundles to the terminal arterioles in the mucosa also contained CGRP‐positive fibres as well as sympathetic nerves (neuropeptide Y‐ and tyrosine hydroxylase positive). It is hypothesized that these epithelial and arteriolar CGRP nerves form the local axon reflex purported to cause neurogenic inflammation.5. The spontaneously active tone exerted by the airway smooth muscle from early in gestation is hypothesized to provide the force across the airway wall and adjacent parenchyma that is the stimulus for lung growth in foetal life.
HUMAN MONOCYTES MAINTAINED IN CULTURE ACQUIRE FUNCTIONAL RESPONSIVENESS TO PLATELET‐ACTIVATING FACTOR THAT IS INDEPENDENT OF INCREASES IN PROTEIN TYROSINE PHOSPHORYLATION
Authors: Grigoriadis George , Stewart Alastair G. 
Published: June 2007

SUMMARY1. Acute (day 0) stimulation with platelet‐activating factor (PAF) did not elicit superoxide anion (02‐) generation from adherent monocytes. However, by day 2 of culture, PAF induced an increase in O2‐ generation that was inhibited by pretreat‐ment with the PAF receptor antagonist WEB 2086.2. The lack of effect of PAF on O2‐ generation was not due to the absence of receptors, as PAF stimulated an increase in tyrosine phosphorylation and intracellular calcium ([Ca2+]i) on both days 0 and 2 of culture.3. Pretreatment with the protein tyrosine kinase inhibitor methyl 2,5‐dihydroxycinnamate inhibited PAF‐induced tyrosine phosphorylation; however, this inhibitor failed to inhibit PAF‐induced O2‐ generation. In contrast, pretreatment with the protein kinase C inhibitor staurosporine had no effect on PAF‐induced tyrosine phosphorylation, but did inhibit PAF‐induced O2‐ generation.4. These results indicate that monocytes maintained in culture acquire a functional response to PAF through a mechanism that appears to be independent of PAF receptor expression, coupling to increases in [Ca2+]i or tyrosine phosphorylation.
PROTEIN PHOSPHORYLATION EVENTS IN EXOCYTOSIS AND ENDOCYTOSIS
Authors: Liu Jun‐Ping 
Published: June 2007

SUMMARY1. Exocytosis and endocytosis are the continuous outward and inward vesicular transports in a cell that occur constantly for intra‐ and inter‐cellular communications. These events are accomplished with the release and uptake of chemical messages fundamental in a variety of cellular functions, such as neurotransmitter release, hormone secretion and receptor internalization.2. Although the mechanisms underlying these events have not been fully established, it is widely accepted that they are largely mediated and controlled by a number of effector proteins. These proteins can operate individually and in concert to produce specialized machineries in the sequential steps of exocytotic and endocytic transports.3. Protein phosphorylation, the most common covalent modification of proteins in cells, has been implicated as playing an important role in the regulation of exocytosis and endocytosis. Many proteins involved in these processes have been identified to be phosphorylated under certain conditions.4. For instance, synapsin I, myristoylated alanine‐rich C kinase substrate and dynamin I undergo dynamic phosphorylation and dephosphorylation cycles during exocytosis and endocytosis, implying that protein phosphorylation regulates the functions of these proteins and, thus, exocytosis and endocytosis.
HISTAMINE‐STIMULATED PHOSPHOLIPASE C SIGNALLING IN THE ADRENAL CHROMAFFIN CELL: EFFECTS ON INOSITOL PHOSPHOLIPID METABOLISM AND TYROSINE HYDROXYLASE PHOSPHORYLATION
Authors: Bunn Stephen J. , Dunkley Peter R. 
Published: June 2007

SUMMARY1. The present report gives a detailed account of histamine‐stimulated phospholipase C (PLC) activity in bovine adrenal chromaffin cells.2. Histamine activation of Hi receptors stimulates PLC with a biphasic sensitivity to extracellular Ca2+. The initial response (the first 15 s stimulation) was not reduced by the removal of extracellular Ca2+, whereas the maintenance of PLC activity beyond this time required Ca2+ influx.3. Phospholipase C activity in response to a 10 min incubation with histamine was inhibited by La3+ (3 mmol/L) or SKF 96365 (10 μmol/L). Nifedipine (10 μ‐mol/L), but not ω‐agatoxin IVA (lOOnmol/L) or co‐conotoxin GVIA (300nmol/L), produced a partial inhibition of PLC activity. The response was also partially inhibited by a reduction in the extracellular CI concentration (40 mmol/L) or by the inclusion of the CL channel blocker /V‐phenylanthranilic acid (300 μmol/L).4. Kinetic analysis of the rate of turnover of the various inositol phosphate isomers in response to histamine suggested that the inositol monophosphates were being produced from a source in addition to inositol 1,4,5‐trisphosphate (Ins(l,4,5)P3) metabolism. This conclusion was supported by the differential action of pertussis toxin and neomycin on Ins(l,4,5)P3 formation compared with inositol monophosphate formation.5. We have attempted to identify a defined role for the intracellular Ca2+ mobilized in these cells in response to histamine. After short incubations (up to 3 min), histamine was able to regulate the site‐specific phosphorylation of tyrosine hydroxylase, the rate‐limiting enzyme in catecholamine synthesis. This observation has important implications for a possible role for the PLC signalling pathway in controlling the rate of catecholamine biosynthesis.
PROPOSAL FOR THE INTERACTION OF NON‐CONVENTIONAL PARTIAL AGONISTS AND CATECHOLAMINES WITH THE ‘PUTATIVE (β‐ADRENOCEPTOR’ IN MAMMALIAN HEART
Authors: Molenaar Peter , Sarsero Doreen , Kaumann Alberto J. 
Published: June 2007

SUMMARY1. Evidence for a ‘putative β‐adrenoceptor’ originated over 20 years ago when cardiostimulant effects were observed to non‐conventional partial agonists. These agonists were originally described as β1‐ and β2‐adrenoceptor antagonists; however, they cause cardiostimulant effects at much higher concentrations than those required to block β2‐ and β2‐adrenoceptors. Cardiostimulant effects of non‐conventional partial agonists have been observed in mouse, rat, guinea‐pig, cat, ferret and human heart tissues.2. The receptor is expressed in several heart regions, including the sinoatrial node, atrium and ventricle.3. The receptor is resistant to blockade by most antagonists that possess high affinity for β1‐ and β2‐adrenoceptors, but is blocked with moderate affinity by (–)‐bupranolol and CGP20712A.4. The receptor is pharmacologically distinct from the β3‐adrenoceptor. Micromolar concentrations of β3‐adrenoceptor agonists have no agonist or blocking activity. The receptor is also resistant to blockade by a β3‐adrenoceptor‐selective antagonist.5. The receptor mediates increases in cAMP levels and cAMP‐dependent protein kinase (PK) A activity in cardiac tissues. Phosphodiesterase inhibition potentiates the positive chronotropic and inotropic effects of non‐conventional partial agonists.6. The receptor mediates hastening of atrial and ventricular relaxation, which is consistent with involvement of a cAMP‐dependent pathway.7. The non‐conventional partial agonist (–)–[3H]–CGP 12177A labels the cardiac putative β4‐adrenoceptor. Non‐conventional partial agonists compete for binding with affinities that are closely similar to their agonist potencies. Catecholamines compete for binding in a stereoselective manner with a rank order of affinity of (–)—R0363> (–)—isoprenaline > (–)—noradrenaline > (–)—adrenaline >> (+)—isoprenaline, suggesting that catecholamines can interact with the receptor.8. The putative β4‐adrenoceptor appears to be coupled to the Gs‐adenylyl cyclase system, which could serve as a guide to its future cloning. Activation of the receptor may plausibly improve diastolic function but could also mediate arrhythmias.
LEVELS OF FRUCTOSYLLYSINE IN COLLAGEN ARE LOW COMPARED WITH THE LOSS OF LYSINE IN DIABETIC RATS: INVOLVEMENT OF OXIDATION IN INCREASED CROSS‐LINKING
Authors: Aoki Yuji , Karasawa Yasuyuki , Yazaki Kunihiko , Shirotori Katsuko , Kawa Shigeyuki , Kiyosawa Kendo 
Published: June 2007

SUMMARY1. It is thought that early glycation products on lysine residues of collagen are re‐arranged to form collagen cross‐links (advanced glycation end‐products), which are increased in hyper‐glycaemia. We have previously reported that 4 week vitamin E supplementation in diabetic rats protected against the development of increased collagen cross‐linking. In the present study we analysed early glycation products as fructosyllysine and amino acid content of tail tendon collagen in rats.2. The amount of lysine residues in early collagen glycation products in diabetic rats was estimated to be less than 0.2 mol/mol type I collagen, whereas in the diabetic rats the loss of lysine residues was estimated to be 2.5 mol/mol. However, vitamin E supplementation protected against the loss of lysine residues without affecting early glycation products.3. Thus, it is demonstrated that the amount of early collagen glycation products is quite small compared with the loss of lysine residues in diabetic rats and we suggest that the oxidative modification of lysine residues may be involved in the increased cross‐linking observed in hyperglycaemia.