Physiological roles and regulation of mammalian sulfate transporters

All cells require inorganic sulfate for normal function. Sulfate is among the most important macronutrients; in cells and is the fourth most abundant anion in human plasma (300 muM). Sulfate is the major sulfur source in many organisms, and because it is a hydrophilic anion that cannot passively cross the lipid bilayer of cell membranes, all cells require a mechanism for sulfate influx and efflux to ensure an optimal supply of sulfate in the body. The class of proteins involved in moving sulfate into or out of cells is called sulfate transporters. To date, numerous sulfate transporters have been identified in tissues and cells from many origins. These include the renal sulfate transporters NaSi-1 and sat-1, the ubiquitously expressed diastrophic dysplasia sulfate transporter DTDST, the intestinal sulfate transporter DRA that is linked to congenital chloride diarrhea, and the erythrocyte anion exchanger AE1. These transporters have only been isolated in the last 10-15 years, and their physiological roles and contributions to body sulfate homeostasis are just now beginning to be determined. This review focuses on the structural and functional properties of mammalian sulfate transporters and highlights some of regulatory mechanisms that control their expression in vivo, under normal physiological and pathophysiological states.

Physiological and symptomatic responses to cycling and walking in intermittent claudication

To shed light on the potential efficacy of cycling as a resting modality in the treatment of intermittent claudication (IC), this study compared physiological and symptomatic responses to graded walking and cycling tests in claudicants. Sixteen subjects with peripheral arterial disease (resting ankle:brachial index (ABI) < 0.9) and IC completed a maximal graded treadmill walking (T) and cycle (C) Lest after three familiarization tests on each mode. During cacti test, symptoms, oxygen uptake (VO2), minute ventilation (V-E), (respiratory exchange ratio) (RER) and heart rate (HR) were measured, and for 10 min after each Lest the brachial and ankle systolic pressures were recorded, All but One subject experienced calf pain as the primary limiting symptom during T whereas the symptoms were more varied during C and included thigh pain, calf pain and dyspnoea, Although maximal exercise time was significantly longer on C than T (690 +/- 67 vs, 495 +/- 57 s), peak VO2, peak, V-E and peak heart rate during C and T were not different; whereas peak RER was higher during C. These responses during C and T were also positively 1, (P < 0.05) with each other, with the exception of RER. The postexercise systolic pressures were also not different between C and T. However, the peak decline ill ankle pressures from resting values after C and T were not correlated with each other. Thew data demonstrate that cycling and walking induce a similar level of metabolic and cardiovascular strain, but that the primary limiting symptoms and haemodynamic response in an individual's extremity, measured after exercise, can differ substantially between these two modes.

Enterohepatic circulation - Physiological, pharmacokinetic and clinical implications

Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.

Physiological responses to the menstrual cycle - Implications for the development of heat illness in female athletes

Fluctuations in estrogen and progesterone during the menstrual cycle can cause changes in body systems other than the reproductive system. For example, progesterone is involved in the regulation of fluid balance in the renal tubules and innervation of the diaphragm via the phrenic nerve. However, few significant changes in the responses of the cardiovascular and respiratory systems, blood lactate, bodyweight, performance and ratings of perceived exertion are evident across the cycle. Nevertheless, substantial evidence exists to suggest that increased progesterone levels during the luteal phase cause increases in both core and skin temperatures and alter the temperature at which sweating begins during exposure to both ambient and hot environments. As heat illness is characterised by a significant increase in body temperature, it is feasible that an additional increase in core temperature during the luteal phase could place females at an increased risk of developing heat illness during this time. In addition, it is often argued that physiological gender differences such as oxygen consumption, percentage body fat and surface area-to-mass ratio place females at a higher risk of heat illness than males. This review examines various physiological responses to heat exposure during the menstrual cycle at rest and during exercise, and considers whether such changes increase the risk of heat illness in female athletes during a particular phase of the menstrual cycle.

Leaf water potential and osmotic adjustment as physiological traits to improve drought tolerance in rice

A sample of recombinant inbred lines (RILs) was derived from a bi-parental cross between Lemont and BK88-BR6, which contrasted in maintenance of leaf water potential (LWP) and expression of osmotic adjustment (OA). Genotypic variation for LWP and OA, and their associations with yield determination under water deficit, was studied in a series of five field experiments. Genotypic variation in the maintenance of high LWP was consistent across water deficit experiments. In the determination of genotypic variation in the maintenance of LWP, rate of water deficit was not an important factor influencing ranking, but degree of water deficit, and phenological development stage were important, particularly around heading. Genotypic variation in expression of OA was also observed under water deficits during both vegetative and flowering stages but ranking was inconsistent across experiments. This was in part because of large experimental errors associated with its measurement, but also because the expression of OA was associated with extent of decline of LWP. The relationship between OA and LWP was demonstrated when data were combined across experiments for vegetative and flowering stages. Under water-limited conditions around flowering, grain yield reduction was mainly due to a increased spikelet sterility. Variation in OA was not related to grain yield nor yield components. There were however, negative phenotypic and genetic correlations between LWP and percentage spikelet sterility measured at flowering stage on panicles at the same development stage during a water deficit treatment. This suggests that traits contributing to the maintenance of high LWP minimized the effects of water deficit on spikelet sterility and consequently grain yield. (C) 2002 Elsevier Science B.V. All rights reserved.

Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The purpose of this study was to determine the pharmacokinetics of [C-14]diclofenac, [C-14]salicylate and [H-3]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. Tc-99m-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac>salicylate >clonidine>sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.

Physiological profiles of restricted endemic plants and their widespread congenors in the North Queensland wet tropics, Australia

Little is known about causes of endemic rarity in plants. This study pioneered an approach that determined environmental variables in the rainforest habitat and generated physiological profiles for light, water, and nutrient relations for three endemically restricted versus widespread congeneric species' pairs. We found no overall consistent differences in the physiological variables between the group of restricted species and the group of widespread species, and congeneric species pairs were therefore examined individually. Availability of soil nutrients did not differ between restricted-widespread species sites suggesting that species grow under comparable nutrient conditions. Under ambient and manipulated higher light conditions, widespread Gardenia ovularis had a greater photosynthetic activity than restricted Gardenia actinocarpa suggesting that the two species differ in their photosynthetic abilities. Differences between Xanthostemon species included lower photosynthetic activity, higher transpiration rate, and a higher foliar manganese concentration in restricted Xanthostemon formosus compared to widespread Xanthostemon chrysanthus. It is suggested that X. formosus is restricted by its high water use to its current rainforest creek edge habitat, while X. chrysanthus grows in a range of environments, although naturally found in riparian rainforest. Restricted Archidendron kanisii had higher electron transport rates, greater dissipative capacity for removal of excess light, and more efficient investment of nitrogen into photosynthetic components, than its widespread relative Archidendron whitei. These observations and previous research suggest that restricted Archidendron kanisii is in the process of expanding its range. Physiological profiles suggest a different cause of rarity for each species. This has implications for the conservation strategies required for each species. (C) 2002 Elsevier Science Ltd. All rights reserved.