Biomedical subjects

D C Button

Publications and source records attributed to D C Button.

6 recordsLinked to original sources

PubMed2001

Factors affecting force loss with prolonged stretching.

The purpose of this study was to investigate the factors underlying the force loss occurring after prolonged, static, passive stretching. Subjects were tested before and 5-10 min following 20 min of static, passive stretching of the quadriceps (N=12) or a similar period of no stretch (control, N=6). Measurements included isometric maximal voluntary contraction (MVC) force, surface integrated electromyographic (iEMG) activity of the quadriceps and hamstrings, evoked contractile properties (twitch and tetanic force), and quadriceps inactivation as measured by the interpolated twitch technique (ITT). Following stretching, there was a significant 12% decrement in MVC with no significant changes in the control group. Muscle inactivation as measured by the ITT and iEMG increased by 2.8% and 20.2%, respectively. While twitch forces significantly decreased 11.7%, there was no change in tetanic force post-stretch. Although possible increases in muscle compliance affected twitch force, a lack of tetanic force change would suggest that post-stretch force decrements are more affected by muscle inactivation than changes in muscle elasticity.

Adult↗

PubMed2000

Mitochondrial control of calcium-channel gating: a mechanism for sustained signaling and transcriptional activation in T lymphocytes.

In addition to their well-known functions in cellular energy transduction, mitochondria play an important role in modulating the amplitude and time course of intracellular Ca(2+) signals. In many cells, mitochondria act as Ca(2+) buffers by taking up and releasing Ca(2+), but this simple buffering action by itself often cannot explain the organelle's effects on Ca(2+) signaling dynamics. Here we describe the functional interaction of mitochondria with store-operated Ca(2+) channels in T lymphocytes as a mechanism of mitochondrial Ca(2+) signaling. In Jurkat T cells with functional mitochondria, prolonged depletion of Ca(2+) stores causes sustained activation of the store-operated Ca(2+) current, I(CRAC) (CRAC, Ca(2+) release-activated Ca(2+)). Inhibition of mitochondrial Ca(2+) uptake by compounds that dissipate the intramitochondrial potential unmasks Ca(2+)-dependent inactivation of I(CRAC). Thus, functional mitochondria are required to maintain CRAC-channel activity, most likely by preventing local Ca(2+) accumulation near sites that govern channel inactivation. In cells stimulated through the T-cell antigen receptor, acute blockade of mitochondrial Ca(2+) uptake inhibits the nuclear translocation of the transcription factor NFAT in parallel with CRAC channel activity and [Ca(2+)](i) elevation, indicating a functional link between mitochondrial regulation of I(CRAC) and T-cell activation. These results demonstrate a role for mitochondria in controlling Ca(2+) channel activity and signal transmission from the plasma membrane to the nucleus.

Calcium Channels↗

PubMed1995

Extrapituitary expression of the rat V1b vasopressin receptor gene.

[Arg8]vasopressin (AVP) stimulates adrenocorticotropic hormone release from the anterior pituitary by acting on the V1b AVP receptor. This receptor can be distinguished from the vascular/hepatic V1a and renal V2 AVP receptors by its differential binding affinities for structural analogous of AVP. Recent studies have shown that the cloned V1a and V2 receptors are structurally related. We have isolated a clone encoding the V1b receptor from a rat pituitary cDNA library using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is a protein of 421 amino acids that has 37-50% identity with the V1a and V2 receptors. Homology is particularly high in the seven putative membrane-spanning domains of these guanine nucleotide-binding protein-coupled receptors. Expression of the recombinant receptor in mammalian cells shows the same binding specificity for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP-stimulated phosphotidylinositol hydrolysis and intracellular Ca2+ mobilization in Chinese hamster ovary or COS-7 cells expressing the cloned receptor suggest second messenger signaling through phospholipase C. RNA blot analysis, reverse transcription PCR, and in situ hybridization studies reveal that V1b receptor mRNA is expressed in the majority of pituitary corticotropes as well as in multiple brain regions and a number of peripheral tissues, including kidney, thymus, heart, lung, spleen, uterus, and breast. Thus, the V1b receptor must mediate some of the diverse biological effects of AVP in the pituitary as well as other organs.

Amino Acid Sequence↗

PubMed1995

Agonist regulation of alpha 1B-adrenergic receptor subcellular distribution and function.

We have monitored agonist-induced alpha 1B-adrenergic receptor (alpha 1BAR) redistribution by immunocytochemical procedures in concert with functional measurements of agonist-elicited [3H]inositol phosphate (InsP) production in human embryonal kidney 293 cells stably expressing alpha 1BAR cDNA (HEK293/alpha 1B). Anti-peptide antibodies directed against the carboxyl-terminal decapeptide of the alpha 1BAR were prepared and shown to react specifically with alpha 1BAR on immunoblots and in situ in HEK293/alpha 1B transfectants. Treatment of HEK293/alpha 1B cells with norepinephrine (10 microM) results in a rapid (5-15 min) and striking internalization of cell surface receptor as visualized by confocal immunofluorescence microscopy. Receptor redistribution is sustained in the presence of agonist, rapidly reversed upon agonist removal, and prevented by the alpha 1 antagonist prazosin. Receptor internalizes to endosomes, as shown by colocalization with transferrin receptor, an endosomal marker. Activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (50 nM) causes receptor endocytosis similar to agonist; agonist-induced internalization is blocked by the PKC inhibitor staurosporine (0.5 microM). In parallel experiments, agonist-induced [3H]InsP production is abolished by phorbol 12-myristate 13-acetate but potentiated by staurosporine. Inhibition of receptor internalization with hypertonic sucrose attenuates agonist-induced [3H]InsP formation; this effect is reversed by concomitant inhibition of PKC with staurosporine. These results suggest that PKC-dependent phosphorylation occurring as a consequence of alpha 1AR stimulation induces receptor desensitization and internalization. Internalized receptor is reactivated and continuously recycled to the cell surface during agonist exposure.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1993

Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain.

Gastric inhibitory polypeptide (GIP), or glucose-dependent insulinotropic peptide, is released from endocrine cells in the small intestine after meals. It is involved in several facets of the anabolic response and is thought to be particularly important in stimulating insulin secretion. We have cloned, functionally expressed, and mapped the distribution of the receptor for GIP. It is a member of the secretin-vasoactive intestinal polypeptide family of G-protein-coupled receptors. When expressed in tissue culture cells, it stimulates cAMP production (EC50 0.3 nM) and also increases intracellular calcium accumulation. GIP receptor mRNA is present in the pancreas as well as the gut, adipose tissue, heart, pituitary, and inner layers of the adrenal cortex, whereas it is not found in kidney, spleen, or liver. It is also expressed in several brain regions, including the cerebral cortex, hippocampus, and olfactory bulb. These results suggest that GIP may have previously undescribed actions. GIP receptor localization in the adrenal cortex suggests that it may have effects on glucocorticoid metabolism. Neither GIP nor its effects have been described in the central nervous system, and mRNA for the known peptide ligand for the receptor cannot be detected in the brain by in situ hybridization or polymerase chain reaction. This suggests that a novel peptide may be present in the brain.

Amino Acid Sequence↗

PubMed1989

Measurement of cytoplasmic calcium concentration in cell suspensions: correction for extracellular Fura-2 through use of Mn2+ and probenecid.

1321N1 astrocytoma cells loaded with Fura-2 were found to continuously transport Fura-2 to the extracellular medium. To correct for extracellular Fura-2 fluorescence a protocol was developed in which Mn2+ was added to duplicate cuvettes of cells to quench extracellular Fura-2 at the beginning and end of the experimental time course. Since the export of Fura-2 was linear with time, two separate quench determinations allowed the amount of fluorescence from extracellular Fura-2 fluorescence to be estimated at every point in the time course and subtracted from the data. The uncorrected and Mn2+-corrected basal cytoplasmic calcium concentrations averaged 153 nM and 72 nM, respectively. The peak intracellular calcium concentrations following muscarinic stimulation with 300 microM carbachol averaged 1159 nM (uncorrected) and 889 nM (Mn2+-corrected). Probenecid (2.5 mM) was found to block the export of Fura-2 from these cells and did not change the basal calcium concentration or the muscarinic calcium response.

Astrocytoma↗