bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion Polymorphism Of Angiotensin‐Converting Enzyme Gene Is Associated With Postprandial Hyperglycaemia In Individuals Undergoing General Check‐Up
Authors: Ohishi Mitsuru , Rakugi Hiromi , Miki Tetsuro , Katsuya Tomohiro , Okamura Atsunori , Kamide Kei , Nakata Yukiko , Takami Seiju , Ikegami Hiroshi , Yanagitani Yoshihiro , Tabuchi Yoshikatsu , Kumahara Yuichi , Higaki Jitsuo , Ogihara Toshio 
Published: March 2003

SUMMARY1. Deletion polymorphism, DD, of the angiotensin‐converting enzyme (ACE) gene is reported to be related to cardiovascular disease, which is frequently based on insulin resistance.2. To clarify the relationship between the ACE genotype DD and plasma glucose increases after an oral glucose load, we performed 75 g oral glucose tolerance test (OGTT) in 301 non‐diabetic men (age range 30–60 years) undergoing general check‐up.3. Insertion/deletion (I/D) polymorphism of the ACE gene was explored using a polymerase chain reaction. The frequency of the II, ID and DD genotypes was 0.43, 0.43 and 0.14, respectively.4. There were no differences in baseline clinical characteristics between subjects with each ACE genotype.5. The mean (±SEM) plasma glucose level at 60 min of the OGTT was significantly higher in subjects with the DD genotype (170.8±6.9 mg/dL) than in subjects with either the II or ID genotype (mean value for two groups 156.6±2.7 mg/dL; P < 0.05). Moreover, the mean percentage change of plasma glucose after 60 min of the OGTT, a marker of plasma glucose increase, was significantly higher in individuals with the DD genotype than in individuals with either the II or ID genotypes.6. In contrast, the mean fasting plasma glucose level, the plasma glucose level at 120 min, the glucose response area and the fasting insulin level were not different between individuals with the DD genotype and individuals with other genotypes.7. In conclusion, subjects with the DD genotype showed transiently higher levels of plasma glucose after an oral glucose load than subjects with other genotypes. Further studies are required to determine whether the association between ACE genotype and postprandial hyperglycaemia influences the incidence of cardiovascular disease and diabetes mellitus.
Cellular Actions Of Opioids And Other Analgesics: Implications For Synergism In Pain Relief
Authors: Christie MacDonald J , Connor Mark , Vaughan Christopher W , Ingram Susan L , Bagley Elena E 
Published: March 2003

SUMMARY1. μ‐Opioid receptor agonists mediate their central analgesic effects by actions on neurons within brain regions such as the mid‐brain periaqueductal grey (PAG). Within the PAG, μ‐opioid receptor‐mediated analgesia results from inhibition of GABAergic influences on output projection neurons. We have established that μ‐opioid receptor activation in the PAG causes a presynaptic inhibition of GABA release that is mediated by activation of a voltage‐dependent K+ channel via 12‐lipoxygenase (LOX) metabolites of arachidonic acid.2. At a cellular level, μ‐opioid agonists have also been shown to open inwardly rectifying K+ channels, close voltage‐gated Ca2+ channels and presynaptically inhibit glutamatergic synaptic transmission in the PAG.3. The μ‐opioid receptor‐mediated presynaptic inhibition of GABAergic transmission was abolished by phospholipase A2 inhibitors and non‐specific LOX and specific 12‐LOX inhibitors. Cyclo‐oxygenase (COX) and specific 5‐LOX inhibitors did not reduce the inhibitory effects of μ‐opioid agonists.4. The opioid actions on GABAergic transmission were mimicked by arachidonic acid and 12‐LOX metabolites, but not 5‐LOX metabolites. The efficacy of μ‐opioids was enhanced synergistically by treatment of PAG neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism, COX and 5‐LOX.5. These results explain a previously described analgesic action of COX inhibitors in the central nervous system that was both independent of prostanoid release and inhibited by opioid receptor antagonists and they also explain the synergistic interaction of opioids with COX inhibitors. These findings also suggest new avenues for the development of centrally active analgesic agents involving combinations of lowered doses of opioids and specific 5‐LOX inhibitors.
Mitochondrial Function In Ischaemia And Reperfusion Of The Ageing Heart
Authors: Pepe Salvatore 
Published: March 2003

SUMMARY1. In addition to Ca2+‐dependent mediation of excitation– contraction coupling during cardiac work and ATP hydrolysis, Ca2+ also stimulates the Krebs’ cycle and mitochondrial matrix dehydrogenases to maintain the nicotinamide adenine dinucleotide redox potential and ATP synthesis. Thus, the balance between energy demand and supply is maintained during increases in cardiac work by elevated cytosolic Ca2+ that is transmitted to the mitochondrial matrix via regulation of uniporter and antiporter pathways across the inner mitochondrial membrane.2. Brief ischaemia perturbs Ca2+ homeostasis but mitochondrial buffering of Ca2+ permits maintained mitochondrial function. However, prolonged ischaemia and reperfusion causes Ca2+‘overload’ at supramicromolar levels. The onset of vicious cycles that abrogate contractile function and, ultimately, may cause irreversible cell injury involves: (i) loss of ionic homeostasis, energy production and anti‐oxidant enzyme activity; (ii) activation of phospholipases; and (iii) accumulation of free radicals, membrane lipid peroxidation products and protein adducts.3. Increased permeability of the inner mitochondrial membrane to solutes occurs causing mitochondrial swelling, ‘proton leak’, reduced efficiency of the respiratory chain and uncoupling of oxidative phosphorylation. The opening of the mitochondrial permeability transition pore is potentiated by high mitochondrial Ca2+ and inducers, such as Pi, long‐chain acyl coenzyme (Co)A and oxygen free radicals. Opening of this channel depolarizes the mitochondrion and dissipates the H+ electrochemical gradient (ΔμH), preventing oxidative phosphorylation. Together with the release of cytochrome c and subsequent activation of caspase pathways, these events precede cell death.4. Compared with younger counterparts, the senescent myocardium has a reduced capacity to recover from ischaemia and reperfusion. The consequent events described above are augmented in ageing. Elevated mitochondrial Ca2+ and increased dehydrogenase activation are linked to inefficient mitochondrial function and limited postischaemic recovery of contractile function.5. Notably, a distinct decrease in the ratio of mitochondrial membrane ω‐3 to ω‐6 polyunsaturated fatty acids (PUFA) and a decrease in the mitochondrial phospholipid cardiolipin occurs in aged rat hearts. A diet rich in ω‐3 PUFA directly increases membrane ω‐3:ω‐6 PUFA and cardiolipin content and also facilitates improved tolerance of ischaemia and reperfusion. A major consequence of dietary ω‐3 PUFA may be the effect of altered mitochondrial Ca2+ flux and Ca2+‐dependent processes.
Effects Of Anaesthesia On Regional Coronary Control Mechanisms
Authors: Cottee DBF , Quail AW , Porges WL , Moore PG , White SW 
Published: March 2003

SUMMARY1. The regional coronary circulation is under the control of local metabolic and myogenic factors, but is also influenced by autonomic systems, including sympathetic and parasympathetic nerves.2. General anaesthetic agents influence not only local control through changes in metabolic demand, but also neural control through suppression of autonomic influence.3. Anaesthetic agents have differing effects on reflex control systems, which are dependent on coronary territory and ventricular rate.4. Effects of anaesthesia should be taken into account when interpreting results in anaesthetized models of coronary control.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: Ion Channels EXPRESSION AND FUNCTION OF COLONIC EPITHELIAL KVLQT1 K+ CHANNELS
Authors: Kunzelmann K , Bleich M , Warth R , Levy‐Holzman R , Garty H , Schreiber R 
Published: March 2003

SUMMARY1. KVLQT1 (KCNQ1) is a voltage‐gated K+ channel essential for repolarization of the heart action potential. Defects in ion channels have been demonstrated in cardiac arrhythmia. This channel is inhibited potently by the chromanol 293B. The same compound has been shown to block cAMP‐dependent electrolyte secretion in rat and human colon. Therefore, it was suggested that a K+ channel similar to KVLQT1 is expressed in the colonic epithelium.2. In the present paper, expression of KVLQT1 and its function in colonic epithelial cells is described. Reverse transcription–polymerase chain reaction analysis of rat colonic mucosa demonstrated expression of KVLQT1 in both crypt cells and surface epithelium. When expressed in Xenopus oocytes, KVLQT1 induced a typical delayed activated K+ current.3. As demonstrated, the channel activity could be further activated by increases in intracellular cAMP. These and other data support the concept that KVLQT1 is forming a component of the basolateral cAMP‐activated K+ conductance in the colonic epithelium.
Intrapituitary Interactions: Another Level Of Endocrine Regulation
Authors: Schwartz Jeff 
Published: March 2003

SUMMARY1. Factors, produced within the anterior pituitary, act locally to influence many acute and developmental changes in neighbouring cells.2. Broad spectra of factors and activities characterize these paracrine interactions.3. Cleavage products of pro‐opiomelanocortin, other than those that act as systemic hormones, are produced by neonatal gonadotrophs and these peptides stimulate mitosis and differentiation of lactotrophs.4. Activins and follistatins exert opposing effects on gonadotrophs. The stimulatory activity of activins is modulated extracellularly through protein–protein interactions with follistatin. Within gonadotrophs, the stimulatory activity of activins is self‐limiting through receptor‐mediated stimulatory and inhibitory signal transduction pathways.5. During the oestrous cycle, the interactions between gonadotroph cells and epidermal growth factor (EGF), acting as a local signal, occur on multiple levels. Levels of expression of EGF receptors on cells vary as a function of the cycle, as do EGF‐induced changes in gene expression and proliferation of cells.
Pharmacology Of A Unique Adenosine Binding Site In Rat Brain Using A Selective Ligand
Authors: Yoshioka Kazuaki , Matsuda Akira , Nakata Hiroyasu 
Published: March 2003

SUMMARY1. In order to further characterize the adenosine binding sites that we previously purified and termed P3 purinergic receptor‐like protein (P3LP), a reliable binding assay method was developed using [3H]‐5′‐N‐ethylcarboxamidoadenosine (NECA) as a radioligand and the newly developed high‐affinity selective ligand 9‐(6,7‐dideoxy‐β‐D‐allo‐hept‐5‐ynofuranosyl) adenine (HAK2701) as a selective displacer.2. Using this assay method, it was found that rat brain membranes possess high‐ and low‐affinity [3H]‐NECA binding sites. The high‐affinity binding site showed KD and Bmax values of 19.7±2.5 nmol/L and 0.192±0.05 pmol/mg protein, respectively, and the KD value for the low‐affinity binding site was 4260±330 nmol/L. The KD value for the high‐affinity site agreed well with that of the [3H]‐NECA binding site determined with the partially purified P3LP preparation described previously.3. The distribution of P3LP in rat tissues was determined using the [3H]‐NECA binding method described above. The highest level of P3LP was in the cerebellum followed by the olfactory bulb and the spinal cord.4. The order of the affinity for various purinergic or related compounds to P3LP in rat brain preparations was also determined by the [3H]‐NECA binding method to be HAK2701 > NECA = adenosine 5′‐O‐(2‐thiodiphosphate) > cAMP = β,γ‐methyleneadenosine 5′‐triphosphate > diadenosine tetraphosphate > α,β‐methyleneadenosine 5′‐triphosphate > 5′‐deoxy‐5′‐methylthioadenosine > N6‐cyclopentyladenosine.5. These studies reveal that the [3H]‐NECA binding assay in combination with HAK2701 is successful in the characterization of P3LP, especially the membrane‐bound form.
Maternal Environment Alters Renal Response To Angiotensin II In The Spontaneously Hypertensive Rat
Authors: Gouldsborough Ingrid , Ashton Nick 
Published: March 2003

SUMMARY1. The level of hypertension displayed by the adult spontaneously hypertensive rat (SHR) may be reduced by 20–30 mmHg if SHR pups are cross‐fostered to a normotensive dam at birth (SHRX). The mechanisms involved are largely unknown, but may involve the kidney and the renin–angiotensin system (RAS) because renal responses to angiotensin (Ang) II are enhanced in the SHR and brief blockade of the RAS in the young rat permanently lowers blood pressure in the SHR. Accordingly, the aim of the present study was to investigate the effect of cross‐fostering on the renal response to AngII in the SHR.2. Renal function was studied in anaesthetized 4‐week‐old SHR, cross‐fostered SHRX and control Wistar‐Kyoto (WKY) rats. Standard clearance methods were used to investigate the renal haemodynamic and tubular effects of AngII. The nitric oxide synthase (NOS) inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) was coinfused in some experiments to abolish the counterbalancing effect of nitric oxide.3. Angiotensin II induced a fall in glomerular filtration rate (GFR) in both SHR and SHRX, but not in WKY rats. This was accompanied by a significant reduction in sodium excretion by SHR but not SHRX pups. This effect appeared to be tubular in origin, because sodium clearance was comparable between the two strains after AngII, but fractional sodium excretion was significantly higher in the SHRX. Coinfusion of the NOS inhibitor L‐NAME had little further effect on sodium excretion in SHR and SHRX, but restored GFR in SHRX to levels comparable with those in WKY rats.4. These data suggest that renal tubular sensitivity to AngII in the SHR can be altered during the early stages of postnatal development, which may contribute to the blood pressure‐ lowering effect of cross‐fostering in the SHR.
Circumventricular Organs: Gateways to the Brain Membrane Properties Of Subfornical Organ Neurons
Authors: Washburn David Ls , Ferguson Alastair V 
Published: March 2003

SUMMARY1. The subfornical organ (SFO) is a forebrain circumventricular structure that plays an integral role in the regulation of fluid balance by acting as the interface between the circulation and the central nervous system. Thus, changes in the activity of SFO neurons can have significant effects on key regulatory loci involved in autonomic control, such as the hypothalamus and medulla.2. Circulating messengers that affect SFO neurons do so through receptor‐mediated regulation of the intrinsic ionic conductances expressed by SFO neurons. It is through the coordinated interaction of the complement of voltage‐gated ion channels that SFO neurons are able to produce unique firing patterns and respond specifically to such a wide range of diverse extracellular messengers.
Circumventricular Organs: Gateways to the BrainApproaches For Gene Delivery To The Subfornical Organ And Magnocellular Neurons
Authors: Vasquez Elisardo C , Meyrelles Silvana S , Chapleau Mark W , Johnson Alan Kim 
Published: March 2003

SUMMARY1. The subfornical organ (SFO), the magnocellular neurons in supraoptic (SON) and paraventricular (PVN) nuclei and the neurohypophysis (NH) constitute an important neuroendocrine axis for the maintenance of cardiovascular and body fluid homeostasis in mammals. The SFO lacks a blood–brain barrier and is an important target for the effects of circulating angiotensin II on thirst. The SON and PVN, which receive projections from the SFO, synthesize the peptide vasopressin, which is stored in the NH nerve terminals and is released into the circulation under conditions of hypovolaemia and hyperosmolality.2. Although neuropharmacological methods are still of fundamental importance for the understanding of the central nervous system (CNS), the techniques of gene transfer to the CNS that have been developed recently provide a new means to study and influence neural function. A key vector for delivering reporter or functional genes to the brain has been replication‐deficient adenovirus, because it is safer, can be generated in high titres, can transfect non‐dividing cells and can be retrogradely transported from nerve terminals to somata.3. In the present review, we describe new approaches that have been developed to transfer genes to the SFO, SON, PVN and NH cells bothin vitroandin vivo. We have defined the adenoviral concentrations required to optimize gene expression without causing cytotoxicity and an inflammatory response in the target cells. Gene transfer is an important tool to reveal mechanisms of SFO and SON control of cardiovascular homeostasis and may provide a therapeutic approach for prevention and/or treatment of pathophysiologies, such as arterial hypertension and genetic diabetes insipidus.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: New Frontiers in Muscle Research The power of single channel recording and analysis: its application to ryanodine receptors in lipid bilayers
Authors: Laver DR 
Published: March 2003

SUMMARY1. Since the inception of the patch‐clamp technique, single‐channel recording has made an enormous impact on our understanding of ion channel function and its role in membrane transport and cell physiology.2. However, the impact of single‐channel recording methods on our understanding of intracellular Ca2+ regulation by internal stores is not as broadly recognized. There are several possible reasons for this.3. First, ion channels in the membranes of intracellular organelles are not directly accessible to patch pipettes, requiring other methods that are not as widely known as the patch‐clamp techniques.4. Second, bulk assays for channel activity have proved successful in advancing our knowledge of Ca2+ handling by intracellular stores. These assays include Ca2+ imaging, ryanodine binding assays and measurements of muscle tension and Ca2+ release and uptake by vesicles that have been isolated from internal stores.5. The present review describes methods used for single‐ channel recording and analysis, as applied to the calcium release channels in striated muscle, and details some of the unique contributions that single‐channel recording and analysis have made to our current understanding of the release of Ca2+ from the internal stores of muscle.6. With this in mind, the review focuses on three aspects of channel function and shows how single‐channel investigations have led to an improved understanding of physiological processes in muscle.7. Finally, the review describes some of the latest improvements in membrane technology that will underpin future advances in single‐channel recording.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: New Frontiers in Muscle Research Does Ca2+ release from the sarcoplasmic reticulum influence heart rate?
Authors: Ju Yue‐Kun , Allen David G 
Published: March 2003

SUMMARY1. The present review summarizes the evidence that Ca2+ release from the sarcoplasmic reticulum (SR) is an important contributor to the systolic rise in [Ca2+]i (the Ca2+ transient) and influences the pacemaker firing rate.2. We believe that the mechanism whereby [Ca2+]i influences firing rate is through the dependence of the Na+–Ca2+ exchanger on [Ca2+]i.3. Extrusion of Ca2+ by the electrogenic Na+–Ca2+ exchanger produces an inward current that contributes to the pacemaker currents. Confocal images of Ca2+ indicate the distribution of [Ca2+]i and Ca2+ sparks add to the evidence that Ca2+ release from SR is involved in pacemaker activity.4. The normal pathway for increased heart rate is sympathetic activation; we discuss the evidence that part of the chronotropic effect of β‐adrenoceptor stimulation is through the modulation of SR Ca2+ release.5. These studies show that Ca2+ handling by the pacemaker cells makes an important contribution to the regulation of pacemaker activity.
Effects Of Milrinone On Left Ventricular End‐Systolic Pressure–Volume Relationship Of Rat Hearts In Situ
Authors: Kishi Takashi , Nakahashi Kazuyoshi , Ito Haruo , Taniguchi Shigeki , Takaki Miyako 
Published: March 2003

SUMMARY1. We have already shown that the left ventricular (LV) end‐systolic pressure–volume relationship (ESPVR) of rat hearts in situ is an upward convex curve and that LV end‐ systolic pressure (ESPmLVV) and the systolic pressure–volume area (PVAmLVV) at a mid‐range LV volume (mLVV) sensitively reflect acute changes in LV contractility and work capability. Milrinone is a non‐glycosidic, non‐sympathomimetic drug that increases myocardial cAMP concentrations by selective inhibition of cardiac phosphodiesterase III. Therefore, milrinone could act on the entire cardiovascular system and cause an increase in inotropy, arterial vasodilatation and venodilatation. The aim of the present study was to investigate whether the approach we have recently instituted is able to detect the effects of milrinone on the entire cardiovascular system.2. We measured simultaneously, in anaesthetized rats, continuous LV pressure using a catheter‐tip micromanometer and LV volume by LV volumetry using a conductance catheter. We obtained steady state LV pressure–volume loops and intermittently obtained the LV ESPVR by gradual occlusion of the ascending aorta. We then evaluated LV function by assessing milrinone‐induced changes in the ESPVR (i.e. ESPmLVV and PVAmLVV) and vasodilator actions by assessing milrinone‐induced changes in ESPESV and effective arterial elastance (Ea), defined as the ESPESV/stroke volume ratio.3. Milrinone (total dose 49.5 μg; infusion rate 3.3–6.7 μg/min, 7–10 μg/kg per min; blood concentration 53.9 ng/mL) largely shifted the ESPVR upwards and, thus, significantly increased end‐systolic pressure (ESP0.08) and the systolic pressure–volume area (PVA0.08) at a mid‐range LV volume (= 0.08 mL/g myocardium). Milrinone also significantly decreased LV ESPESV and decreased Ea, although these decreases were not significant.4. The results of the present study suggest that our own recently instituted approach to evaluate LV function by measuring LV pressure–volume loops and ESPVR succeeded in detecting a cardiotonic action of milrinone with arterial vasodilatation in normal rat hearts.