Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the capillary recruitment hypothesis in brain, cerebral blood flow was raised markedly in rats by exposure to 8% CO2 (hypercapnia), and capillary permeability-surface area (PS) products were measured. Local cerebral blood flow (LCBF), volume of radiolabeled blood in parenchymal microvessels (also referred to as the blood space or Vb), plus the local capillary influx rate constants (K1) and PS products of [14C]antipyrine and 3-O-[14C]methyl-D-glucose (3OMG) were estimated in 44 brain areas. Hypercapnia raised PaO2 to 140 mm Hg, elevated LCBF by two- to threefold through out the brain, and increased Vb from 5 to 33% (mean = 22%) in 42 of 44 brain areas; hypercapnia did not, however, alter microvessel hematocrit. With hypercapnia, the influx of antipyrine was increased by 40-65% in all brain areas, and the PS products of antipyrine were elevated from 0-35% (mean = 17%). The PS products of antipyrine plus the parenchymal blood spaces suggest modest (< 30%) capillary recruitment in most brain areas as well as some microvessel dilation, mainly in forebrain gray matter and white matter areas. In contrast, hypercapnia did not appreciably alter K1 nor PS of 3OMG; it slightly but not significantly raised the blood levels of glucose. In view of the blood space and antipyrine evidence for modest capillary recruitment and vasodilation, the lack of change in PS of 3OMG implies that glucose transporter activity was lowered by hypercapnia, an effect similar to that reported for high-dose pentobarbital. Finally, the microvessel hematocrit and 3OMG data suggest that cerebral capillary permeability (P) was not increased by hypercapnia. Overall, hypercapnia seems to increase LCBF mainly by raising the velocity of blood flow; capillary recruitment and dilation appear to play relatively minor roles in this flow increase.
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PMID:Slightly altered permeability-surface area products imply some cerebral capillary recruitment during hypercapnia. 785 5

The ventral medullary surface (VMS) of the medulla oblongata is known to be the site of the central chemosensitive neurons in mammals. These neurons sense excess H+/CO2 dissolved in the CSF and induce hyperventilation. To elucidate the mechanism of neuronal cell adaptation to changes of H+/CO2, we screened for hypercapnia-induced genes in the VMS. Here, we report cloning and characterization of a novel gene called proton-associated sugar transporter-A (Past-A), which is induced in the brain after hypercapnia and mediates glucose uptake along the pH gradient. Past-A comprises 751 amino acid residues containing 12 membrane-spanning helices, several conserved sugar transport motifs, three proline-rich regions, and leucine repeats. Past-A transcript was expressed predominantly in the brain. Moreover, the Past-A-immunoreactive neural cells were found in the VMS of the medulla oblongata, and the number of immunoreactive cells was increased by hypercapnic stimulation. Transient transfection of Past-A in COS-7 cells leads to the expression of a membrane-associated 82 kDa protein that possesses a glucose transport activity. The acidification of extracellular medium facilitated glucose uptake, whereas the addition of carbonyl cyanide m-chlorophenylhydrazone, a protonophore, inhibited glucose import. Together, our results indicate that Past-A is a brain-specific glucose transporter that may represent an adaptation mechanism regulating sugar homeostasis in neuronal cells after hypercapnia.
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PMID:Past-A, a novel proton-associated sugar transporter, regulates glucose homeostasis in the brain. 1241 39

The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous systems, cerebrospinal fluid and blood, exocrine (pancreas, salivary, lacrimal) as well as endocrine (pancreatic islets, pituitary, adrenal) glands. Several factors including stress, glucagon-like peptide-1 agonists, glutamate, nicotine, glucose, and hypoglycaemia stimulate the expression of Hcrt/orexin system, but it is inhibited by ageing, bone morphogenetic protein, hypoxia/hypercapnia, melanocortin receptor accessory protein 2, and glucagon. Literature reports show that Hcrt/orexin can significantly increase insulin secretion from normal and diabetic rat pancreata. Hcrt/orexin decreases blood glucose concentration and reduces insulin resistance partly via increased tissue expression of glucose transporter type 4. It reduces obesity by increasing browning of fat cells and energy expenditure. Taken together, Hcrt/orexin modulates obesity and the metabolism of glucose and insulin. The Hcrt/orexin system may thus be a target in the development of new therapies for the treatment of diabetes mellitus.
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PMID:Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin. 3165 12