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Biomedical subjects

D M Gross

Publications and source records attributed to D M Gross.

52 records · Page 3Linked to original sources
PubMed1978

Studies on the characterization of isolated renin-containing granules: the storage form of renin.

Renin-containing granules isolated by isopycnic zonal centrifugation were partially characterized biochemically. Extracts of the granules were found to have a dual pH optimum at 5.5-6.0 and 7.0-7.5 and possess linear time-dependence of product formation when reacted with homologous renin substrate. Extracts also possessed a first order reaction constant of 0.713 X 10(-2). Treatment of the extracts with ammonium sulfate increased the velocity of the renin/renin substrate reaction though it continued to be linear with respect to time. This partially purified renin preparation was found to have a Km=3.9 X 10(3) ng/ml. Gel filtration of this preparation of renin demonstrated the presence of an active protein with renin activity and a molecular weight of 59,000 daltons in addition to an inactive protein of molecular weight 13, 750 daltons which may be a potential inhibitor of the renin/renin substrate reaction. The former protein or "big renin" may be the storage form or porhormone state of renin within the renin-containing granules of the juxtaglomerular cells.

Angiotensin I↗
PubMed1978

Effects of terbutaline, a synthetic beta adrenoceptor agonist, on in vivo erythropoietin production.

Terbutaline sulfate, a new synthetic beta2-adrenoceptor agonist, was found to produce a dose-related increase in 59Fe-incorporation into newly formed red blood cells of exhypoxic polycythemic mice. This effect was blocked by prior treatment of the polycythemic mice with the potent beta-adrenoceptor antagonist, DL-propranolol. Terbutaline was also infused (i.v.) (500 microgram/kg/min) into restrained unanesthetized rabbits for a period of 5 hr with constant monitoring of arterial blood pressure and periodic blood Po2, Pco2, and pH analyses. Terbutaline was found to significantly elevate plasma erythropoietin titers in rabbits while producing a slight but nonsignificant decrease in mean blood pressure. Terbutaline did not produce a significant effect upon blood gases or blood pH. These data suggest a possible involvement of beta2-adrenoceptor activation of erythropoietin production.

Animals↗
PubMed1978

The effects of arachidonic acid on erythropoietin production in exhypoxic polycythemic mice and the isolated perfused canine kidney.

The ability of arachidonic acid (AA), the bisenoic prostaglandin precursor to stimulate erythropoiesis and erythropoietin (Ep) production in exhypoxic polycythemic mice and the programmed isolated perfused canine kidney was investigated. Arachidonate in the lowest dose tested (50 microgram/kg i.p.) maximally stimulated erythropoiesis when administered to exhypoxic polycythemic mice. Kidneys from dogs made hypoxic for 4 hr at 0.42 atm pressure were perfused (2--3 ml/g/min, 37 degrees C) in a closed circuit system for 5 hr with blood from nonhypoxic donors. AA infusion (80 microgram/min) caused a significant (P less than .05) increase in erythropoietic activity of the perfusate as measured by the percentage of 48-hr 59Fe incorporation into red blood cells of exhypoxic polycythemic mice per milliliter of perfusate from an initial value of 1.66 +/- 0.50% to 6.05 +/- 0.96% over the 1st hr of infusion whereas vehicle controls showed no change. To determine whether this increase in Ep production was dependent on biosynthesis of renal prostaglandins and their intermediates, the ability of indomethacin to block AA-induced Ep production was studied. When kidney donors were twice pretreated with indomethacin 12 hr and immediately before their hypoxic exposure, no increase in Ep titers were seen during AA infusion. These results support the hypothesis that endogenously synthesized prostaglandins, their intermediates and/or other products of AA metabolism, such as prostacyclin and prostaglandins play an important role in the control Ep production.

Animals↗
PubMed1976

Enhanced erythropoietin and prostaglandin E production in the dog following renal artery constriction.

Renal artery constriction (RAC) to 30% of normal flow for 12 hr in the unilaterally nephrectomized dog produced a marked increase in both erythropoietin titers and prostaglandin E (PGE) levels in the blood. In dogs pretreated prior to RAC with indomethacin, a potent inhibitor of prostaglandin synthetase, there was no significant increase in either PGE or erythropoietin levels as compared to zero-time control values. These data suggested an involvement of renal PGE in the generation of erythropoietin following RAC.

Animals↗
PubMed1976

Effects of prostaglandins A2, E2 and F2 alpha on erythropoietin production.

The erythropoietic effects of the renal prostaglandins were investigated in exhypoxic polycythemic mice and in isolated perfused dog kidneys. Prostaglandins A2 and E2 in a dose range of 100 to 800 mug/kg b.wt. were found to produce a dose-related increase in radioactive iron incorporation in red cells. Prostaglandin F2 alpha was devoid of an erythropoietic effect in polycythemic mice. In that PGE2 is the principal renal prostaglandin, PGE2 (0.5 mug/min) or saline was infused into isolated perfused dog kidneys that had been programmed by prior exposure to hypoxia (0.42 atm) for 4 hours. PGE2-infused kidneys during 5 hours of perfusion with blood from nonhypoxic donor dogs produced significant increases in perfusate titers of erythropoietin when compared with that of saline infusion controls at the same time intervals. These data suggest an involvement of the renal prostaglandin PGE2 in erythropoietin production by the kidney.

Animals↗
PubMed1975

The large-scale isolation of renin-containing granules from rabbit renal cortex by zonal centrifugation.

A new method for the isolation of renin-containing granules from rabbit renal cortex by sequential two-dimensional centrifugation is presented. A mitochondrial fraction produced by preparative differential centrifugation was subjected to isopycnic centrifugation on combined discontinuous and linear density gradients in the same SZ-14 reorienting gradient zonal centrifuge rotor. Renin activity, as assayed by radioimmunoassay for angiotensin I, was localized in a region of the density gradient with a corresponding density of 1.196 Gm. per cubic centimeter or 1.53 M sucrose. The renin-containing granules were enriched 5.0-fold over whole homogenate levels, while peroxisomes were enriched 17.4-fold, lysosomes 23.4-fold, and mitochondria 4.3-fold. Electron microscopic examination of the fraction with highest renin activity showed a granular fraction almost free of contamination from other subcellular material. The data supports the view that renin-containing granules are a distinct subcellular particle. This new method for the large-scale isolation of renin-containing granules makes it possible to obtain the quantity of material necessary to study the release renin at the subcellular level and permit the further biochemical purification and characterization of the enzyme.

Acid Phosphatase↗
PubMedDate not supplied

Inhibition of mammalian soluble guanylate cyclase activity by adenosine 5'-tetraphosphate, guanosine 5'-tetraphosphate and other nucleotides.

The effects of a variety of purine and pyrimidine nucleotides were tested for their capacity to inhibit mammalian soluble guanylate cyclase activity. Adenosine 5'-tetraphosphate (ATetP), ATP, ADP, AMP, guanosine 5'-tetraphosphate (GTetP) and GDP were found to inhibit soluble guanylate cyclase activity from rat lung and other mammalian tissues. The corresponding cytosine and thymine nucleotides showed little or no inhibitory activity, except for thymidine 5'-tetraphosphate, which inhibited glanylate cyclase activity but to a lesser extent than did the purine nucleoside tetraphosphates. ATetP and GTetP were found to be potent inhibitors of soluble guanylate cyclase activity from rat, guinea pig and mouse lung, rat heart and rat brain. Both purine nucleoside tetraphosphates were competitive inhibitors of the rat lung soluble enzyme. ATetP and GTetP had Ki values of 1 muM and 2.5 muM, respectively. The experimental data suggest that purine nucleoside tetraphosphates, and perhaps other purine nucleotides, may play a biologic role in modulating mammalian soluble guanylate cyclase activity.

Adenine Nucleotides↗