Regulation of renal tubular secretion of organic compounds. (65/794)

BACKGROUND: Information on the molecular basis underlying organic anion and cation transport in renal tubules has expanded in recent years with the identification and characterization of numerous transporters. However, little is known about the regulation of this transport. METHODS: Both English and Russian language studies dealing with the regulation of organic ion transport by the kidney have been reviewed. RESULTS: This review summarizes the literature on the physiological and pharmacological aspects of the regulation of organic ion transport, linking this information where possible to underlying transport mechanisms. Current models of the tubular secretion of organic anions and cations are reviewed. Factors that inhibit or enhance tubular secretion of xenobiotics are described, and their influence on proximal tubule cell transport and function is discussed. Important roles for substrate stimulation, the adrenergic nervous system, numerous hormones, P-glycoprotein, and protein kinase C activity have been identified. CONCLUSIONS: Despite considerable advances in the understanding of basic transport pathways and mechanisms involved in the tubular secretion of organic compounds, there is still relatively little information on the regulation of this transport. Studies combining the techniques of integrative and cell physiology and molecular biology will provide significant new insights into the pathways regulating the tubular transport of these compounds.  (+info)

An inducer of molluscan metamorphosis transforms activity patterns in a larval nervous system. (66/794)

Larvae of the nudibranch mollusc Phestilla sibogae metamorphose in response to a small organic compound released into seawater by their adult prey, the scleractinian coral Porites compressa. The transformations that occur during metamorphosis, including loss of the ciliated velum (swimming organ), evacuation of the shell, and bodily elongation, are thought to be controlled by a combination of neuronal and neuroendocrine activities. Activation of peripheral chemosensory neurons by the metamorphosis-inducing compound should therefore elicit changes within the central nervous system. We used extracellular recording techniques in an attempt to detect responses of neurons within the larval central ganglia to seawater conditioned by P. compressa, to seawater conditioned by the weakly inductive coral Pocillopora damicornis, and to non-inductive seawater controls. The activity patterns within the nervous systems of semi-intact larvae changed in response to both types of coral exudates. Changes took place in two size classes of action potentials, one of which is known to be associated with velar ciliary arrests.  (+info)

Nutrient-dense foods and exercise in frail elderly: effects on B vitamins, homocysteine, methylmalonic acid, and neuropsychological functioning. (67/794)

BACKGROUND: Frail elders are at risk of suboptimal micronutrient status, functional decline, and neurologic disorders. The influence of oral multimicronutrients in physiologic doses and of moderately intense physical exercise on homocysteine (Hcy), methylmalonic acid (MMA), and neurologic functioning have not yet been investigated. OBJECTIVE: Our goal was to determine the effects of enriched foods and exercise on blood vitamins, Hcy, MMA, and neuropsychological functioning in the frail. DESIGN: A 17-wk randomized controlled intervention trial was used to study 1) enriched foods plus a social program, 2) regular foods plus exercise, 3) enriched foods plus exercise, and 4) regular foods plus a social program. Enriched foods contained multiple micronutrients (25-100% of the Dutch recommended dietary allowances); exercises focused on strength, coordination, flexibility, and endurance. Vitamin (cobalamin, red blood cell folate, and pyridoxal 5'-phosphate), Hcy, and MMA concentrations were measured and 2 neuropsychological tests were conducted. RESULTS: Vitamin concentrations were higher in the supplemented groups than in the unsupplemented groups (P < 0.001; total n = 130). Compared with baseline, cobalamin in the supplemented groups was increased by 22%, plasma folate by 101%, red blood cell folate by 87%, and pyridoxal 5'-phosphate by 68%. Concentrations in the unsupplemented groups changed by -2%, -6%, 1%, and -13%, respectively. Hcy decreased by 25% and MMA by 30% in the supplemented groups, compared with a small increase in Hcy (2%) and decrease in MMA (9%) in the unsupplemented groups. Exercise did not significantly affect vitamin, Hcy, or MMA concentrations. No significant effect of either intervention was observed on the neuropsychological tests. CONCLUSIONS: The decrease in Hcy and MMA in frail elders confirms a subclinical metabolic deficiency state. Enriched foods containing physiologic amounts of micronutrients have a beneficial effect on these metabolites. No effects of B vitamins on mental health were identified.  (+info)

Mouse genetics in cell biology. (68/794)

Genetic methodologies have provided powerful means for investigating the cellular and molecular mechanisms of biological functions. Cell-cell and cell-extracellular matrix interactions in particular have been studied in different functional systems with genetically modified animals. In the peripheral and central nervous system, many aspects of specific processes based on such interactions, including myelination, synaptic transmission and plasticity, have been elucidated at the cellular and molecular level. Importantly, genetic approaches have greatly advanced the understanding of pathologies resulting from impaired cellular interactions in the brain and the periphery. In this review, some of the most relevant genetic mouse models in cell biology and the methodologies employed for their production will be described. In addition their usefulness for studies of the mechanisms of hereditary neuropathies, learning and memory, and tumorigenesis will be illustrated.  (+info)

The neurogenic vasodilator response to endothelin-1: a study in human skin in vivo. (69/794)

We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 microM ET-1 (1.43 +/- 0.64 microM, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 +/- 0.38 microM) whilst that in the flare increased to reach a peak value of 2.28 +/- 0.61 microM at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ET(A)/ET(B) antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced pallor and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo.  (+info)

Positive and negative feedback mechanisms in the neural regulation of cardiovascular function in healthy and spinal cord-injured humans. (70/794)

BACKGROUND: We tested the hypothesis that in humans, hypertension/tachycardia and hypotension/bradycardia nonbaroreflex sequences that occur within spontaneous arterial pressure (AP) and R-R interval fluctuations are an expression of positive feedback mechanisms neurally regulating the cardiovascular system. METHODS AND RESULTS: We studied 15 spinal cord-injured (SCI) subjects (8 tetraplegics and 7 paraplegics) and 8 healthy subjects. The occurrence of nonbaroreflex (NBseq) and baroreflex (Bseq) sequences, ie, hypertension-bradycardia and hypotension-tachycardia sequences, was assessed during rest and head-up tilt (HUT). The ratio between Bseq and NBseq (B/NB ratio) was also calculated. In resting conditions, the occurrence of NBseq was significantly lower (P:<0.05) in tetraplegics (7.9+/-1.5) than in paraplegics (16.2+/-3.2) and normal subjects (19.0+/-3.5), whereas the occurrence of Bseq was not significantly different between the 3 groups (38.6+/-11.9 versus 45.4+/-6.0 versus 47.0+/-11.9). In tetraplegics, the B/NB ratio showed a marked, significant decrease (from 8.4+/-4.2 to 1.9+/-0.8, P:<0.05) in response to HUT, whereas in normal subjects, it showed a significant increase (from 3.5+/-0.7 to 9.4+/-2.7, P:<0.05). In paraplegics, the B/NB ratio did not change significantly in response to HUT (from 4.5+/-1.6 to 4.8+/-1.1). CONCLUSIONS: Our data suggest that nonbaroreflex sequences occur in humans and might represent the expression of an integrated, neurally mediated, feed-forward type of short-term cardiovascular regulation that is able to interact dynamically with feedback mechanisms of baroreflex origin.  (+info)

Nervous control of light responses in the sea anemone, Calamactis praelongus. (71/794)

1. The burrowing sea anemone, Calamactis praelongus, responds to light with local, non-nervous contractions of the column. There are also more extensive responses of the column and retractor muscles co-ordinated by nerve net pulses (NNP's) under pacemaker control. 2. NNP's occur in at least two types of bursts and in sequences which sometimes indicate a rotating site of pulse initiation. 3. Light-evoked NNP sequences can be tape recorded and used later to drive a stimulator to reproduce the original sequences in the same or different anemones, evoking muscular responses which approximate the originals. This technique separates the pacemaker-directed component of the light response from the local effects of light stimulation. 4. Isolated circular and parietal muscles contract slowly when stimulated by light or excited indirectly by NNP's. Retractor muscles are insensitive to light but produce rapid contractions when excited by closely spaced light-evoked NNP's. 5. A model for light responses is proposed which incorporates the characteristics of isolated muscles and intact anemones.  (+info)

Neural processing of gravito-inertial cues in humans. II. Influence of the semicircular canals during eccentric rotation. (72/794)

All linear accelerometers, including the otolith organs, respond equivalently to gravity and linear acceleration. To investigate how the nervous system resolves this ambiguity, we measured perceived roll tilt and reflexive eye movements in humans in the dark using two different centrifugation motion paradigms (fixed radius and variable radius) combined with two different subject orientations (facing-motion and back-to-motion). In the fixed radius trials, the radius at which the subject was seated was held constant while the rotation speed was changed to yield changes in the centrifugal force. In variable radius trials, the rotation speed was held constant while the radius was varied to yield a centrifugal force that nearly duplicated that measured during the fixed radius condition. The total gravito-inertial force (GIF) measured by the otolith organs was nearly identical in the two paradigms; the primary difference was the presence (fixed radius) or absence (variable radius) of yaw rotational cues. We found that the yaw rotational cues had a large statistically significant effect on the time course of perceived tilt, demonstrating that yaw rotational cues contribute substantially to the neural processing of roll tilt. We also found that the orientation of the subject relative to the centripetal acceleration had a dramatic influence on the eye movements measured during fixed radius centrifugation. Specifically, the horizontal vestibuloocular reflex (VOR) measured in our human subjects was always greater when the subject faced the direction of motion than when the subjects had their backs toward the motion during fixed radius rotation. This difference was consistent with the presence of a horizontal translational VOR response induced by the centripetal acceleration. Most importantly, by comparing the perceptual tilt responses to the eye movement responses, we found that the translational VOR component decayed as the subjective tilt indication aligned with the tilt of the GIF. This was true for both the fixed radius and variable radius conditions even though the time course of the responses was significantly different for these two conditions. These findings are consistent with the hypothesis that the nervous system resolves the ambiguous measurements of GIF into neural estimates of gravity and linear acceleration. More generally, these findings are consistent with the hypothesis that the nervous system uses internal models to process and interpret sensory motor cues.  (+info)