ABSTRACT
We examined the effect of the X-linked hypophosphatemic Gy mutation on the maximal renal tubular reabsorption of phosphate (TmP) and compared the effects of phosphate deprivation on both TmP and Na(+)-dependent phosphate transport in renal brush-border membrane vesicles (BBMV). Adult female normal and Gy mice were fed a control (1.0% P) or low-phosphate (0.03% P) diet for 5 days. For TmP measurement, anesthetized mice were infused intravenously with [3H]inulin and increasing increments of phosphate (0, 0.27, 0.54, and 1.08 mumol/min). TmP was significantly reduced in Gy mice on the control diet. Normal mice responded to the low-phosphate diet by raising their TmP [2.35 +/- 0.12 (n = 9) vs. 3.71 +/- 0.16 (n = 9) mumol/ml glomerular filtrate, mean +/- SE, P < 0.001], whereas in Gy mice, the change was not significant [1.46 +/- 0.10 (n = 10) vs. 1.70 +/- 0.11 (n = 10)]. In contrast, Gy mice did respond to phosphate restriction by increasing the initial-rate Na(+)-dependent phosphate transport in the renal BBMV [314 +/- 11 (n = 5) vs. 1,105 +/- 157 (n = 5) pmol.mg protein-1.6 s-1, P < 0.01] as did normal mice [583 +/- 64 (n = 5) vs. 1,692 +/- 203 (n = 5) pmol.mg protein-1.6 s-1, P < 0.01]. In conclusion, the adaptive increase in Na(+)-phosphate cotransport in the brush-border membrane of the proximal tubule is not sufficient for the overall increase in TmP in the whole kidney in response to dietary phosphate deprivation.
Subject(s)
Hypophosphatemia/genetics , Hypophosphatemia/metabolism , Kidney Tubules/metabolism , Microvilli/metabolism , Phosphates/deficiency , Phosphates/metabolism , X Chromosome , Absorption , Animals , Biological Transport , Crosses, Genetic , Diet , Female , Genotype , Glomerular Filtration Rate , Heterozygote , Kidney Tubules/physiology , Kidney Tubules/physiopathology , Male , Mice , Mice, Inbred C3H , Mice, Mutant Strains , Phosphates/blood , Reference ValuesSubject(s)
Skin Transplantation , Animals , Female , Methods , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Surgical Staplers , Sutures , Transplantation, HomologousSubject(s)
Burns/therapy , Infusions, Parenteral , Shock, Traumatic/prevention & control , Temperature , Animals , Body Temperature , Body Weight , Burns/metabolism , Burns/mortality , Disease Models, Animal , Drinking Behavior , Feeding Behavior , Female , Glucose/administration & dosage , Hindlimb , Injections, Subcutaneous , Mice , Nitrogen/urine , Shock, Traumatic/metabolism , Shock, Traumatic/mortality , Sodium Chloride/administration & dosage , Tourniquets , Water , Water-Electrolyte BalanceSubject(s)
Hypersensitivity, Delayed , Immunity, Cellular/drug effects , Lectins/pharmacology , Transplantation Immunology/drug effects , Animals , DNA/biosynthesis , Drug Antagonism , Female , Galactose/pharmacology , Glucose/pharmacology , Graft Rejection/drug effects , Hexosamines/pharmacology , Humans , Immunodiffusion , In Vitro Techniques , Lectins/antagonists & inhibitors , Lymphocytes/metabolism , Mice , Skin Transplantation , Stimulation, ChemicalSubject(s)
Shock, Septic/immunology , Shock, Traumatic/immunology , Skin Transplantation , Transplantation Immunology , Animals , Burns , Escherichia coli , Female , Graft Rejection , Hypertonic Solutions , Lipopolysaccharides , Male , Mice , Mice, Inbred Strains , Polysaccharides, Bacterial , Shock, Septic/physiopathology , Shock, Traumatic/physiopathology , Time Factors , Tourniquets , Transplantation, HomologousABSTRACT
1. 5-Hydroxytryptamine (5-HT), tryptamine, 5-methyltryptamine, 5-methoxytryptamine, N-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine, and histamine markedly protect mice subjected to burn, tourniquet and endotoxin shock. All of these compounds protect when given 30 min before the production of shock, but not when administered afterwards.2. The above compounds, as well as purines and purine derivatives have a similar chemical structure. Protection requires the compounds to contain a 5-membered ring with one unsubstituted N atom and a side chain with a basic N atom three atoms from the ring.3. All other biological amines tested without this chemical structure did not protect.4. Since the simplest compounds containing all the prerequisites for protection is histamine, this compound may play the key role in protection, for both 5-HT and purines release histamine from tissues.5. Protective doses of 5-HT and histamine prevent swelling of the injured area after tourniquet trauma and produce an increased bleeding volume and lower haematocrit value after burning. These actions of the drugs on the circulation may account for the increased survival after thermal trauma.
