PubMed Health⌕ Search

Biomedical subjects

C R Creveling

Publications and source records attributed to C R Creveling.

At least 73 records · Page 4Linked to original sources
PubMed1980

Membrane potentials in cell-free preparations from guinea pig cerebral cortex: effect of depolarizing agents and cyclic nucleotides.

The distribution of [3H]triphenylmethylphosphonium ion between the medium and vesicular entities was examined in a cell-free, particulate preparation from guinea pig cerebral cortex. This distribution followed the Nernst relationship with regard to the external potassium ion concentration and, in physiological media, indicated the maintenance of a mean trans-membrane potential ranging from -58 to -78 mV. The neurotoxins batrachotoxin, veratridine, and grayanotoxin I, partially depolarized the preparation. Tetrodotoxin blocked the depolarization by batrachotoxin, veratridine, and gray-anotoxin I. The depolarization by these neurotoxins was potentiated by the presence of anemone toxin II and presumably reflected the response of vesicular components of neuronal origin. An additional potassium-sensitive depolarization probably represented the response of vesicular components of glial origin with an apparent transmembrane potential of -8 to -35 mV. No correlation could be demonstrated between changes in transmembrane potential and stimulation of cyclic AMP generation by a variety of agents in this preparation.

Animals↗
PubMed1980

Immunocytochemical localization of catechol-O-methyltransferase in the pregnant rat uterus.

Light microscopic immunocytochemical observations of catechol-O-methyl-transferase (COMT) localization in the pregnant rat uterus were made with a specific antibody to soluble rat liver COMT and the peroxidase-antiperoxidase technique. The changes in cellular localization of COMT were followed from the onset of pregnancy to 12 h after delivery of the last fetus. COMT first appeared on day 5 of pregnancy in endometrial epithelial cells of the uterus. On day 7, COMT appeared in the decidual cells on the antimesometrial side of the uterus close to the implanting blastocyst. Two morphologically distinct, COMT-positive, decidual cells were observed: polygonal cells and stellate cells. After parturition, COMT-positive decidual cells remained in the decidua basalis. The possible physiological roles of COMT in the pregnant uterus are discussed.

Animals↗
PubMed1980

Effects of ring fluorination on the cardiovascular actions of dopamine and norepinephrine in the dog.

The 2-, 5- and 6-fluoro (F) analogs of dopamine (DA) and (+/-)-norepinephrine (NE) were compared with the respective parent molecules for alpha, beta-1 and beta-2 adrenergic and vascular DA activities in pentobarbital-anesthetized dogs. 2-F and 5-F DA were equipotent while 6-F DA was about 4-fold less active than DA in causing renal vasodilation in phenoxybenzamine pretreated dogs (vascular DA activity). The three analogs were indistinguishable from DA for vasoconstrictor activity in the femoral vascular bed (alpha adrenergic activity). 2-F and 6-F DA were equipotent to DA while 5-F was about 2-fold more active than DA in inotropic activity (beta-1 adrenergic activity). In contrast, F NE analogs showed marked differential activities. 2-F NE resembled isoproterenol in increasing cardiac contractility, lowering diastolic blood pressure and causing vasodilation in the femoral vascular bed. The 5-F analog was the most potent for (beta-1 adrenergic activity and produced biphasic effects on blood pressure and the femoral vascular bed. 6-F NE exerted no inotropic activity in dose 50- to 80-fold higher than the threshold dose of l-NE and caused vasoconstriction. Thus, fluorine substitution in either of the three positions in the benzene ring of DA induced only minor, if any, differences in receptor activation when compared with DA. On the other hand, fluorine substitution in the benzene ring of NE yielded compounds with marked differential receptor activity. These data indicate that the differences between the effects of F substitution on DA and NE analogs must be related to the only structural difference between the two catecholamines, the presence of a beta-hydroxyl group in NE.

Animals↗
PubMed1979

Effect of fluorine substitution on the agonist specificity of norepinephrine.

Substitution of fluorine for hydrogen in position 2, 5, or 6 of the aromatic ring of norepinephrine markedly alters the alpha- and beta-adrenergic agonist properties of norephinephrine. The 6-fluoro isomer is an beta-adrenergic agonist with virtually no beta agonist activity, while the 2-fluoro isomer is a beta-adrenergic agonist with little alpha activity. The 5-fluoro isomer is equipotent with norepinephrine as an alpha agonist and significantly more potent as a beta agonist. The possible physiochemical basis for these differences is discussed.

Animals↗
PubMed1979

Immunohistochemical demonstration of catechol-o-methyltransferase in mammalian brain.

Catechol-O-methyltransferase (COMT)(EC 2.1.1.6) was localized using fluorescence immunohistochemistry in rat liver and kidney and in rat, chinchilla, and bovine brains. In the brain, specific fluorescence was visable only in non-neuronal cellular elements in all three species. Ventricular ependymal cells and cells of the choroid plexuses exhibited the greatest intensity of immunofluorescence. Glial immunofluorescence appeared prominently in large myelinated fiber tracts. Interfascicular and perineuronal satellite oligodendrocytes as well as fibrous astrocytes were immunoreactive, though myelin itself did not exhibit a positive reaction. Bergmann glial cells in the cerebellum also stained brightly for COMT. Although this study indicates that the predominant localization of COMT is non-neuronal, it is important to note that the presence of small quantities of this enzyme in neurons cannot be excluded. The patterns of localization observed in the non-neuronal elements suggest that this enzyme may function as a barrier to free diffusion of catechol compounds within the central nervous system.

Animals↗
PubMed1979

Calcium-dependent cyclic nucleotide phosphodiesterase. Inhibition of basal activity by heat-stable factors from rat cerebrum.

The boiled supernatant fraction from rat cerebrum contained factors which inhibited the basal activity of a Ca2+-dependent phosphodiesterase from rat cerebrum. Two inhibitory fractions were isolated by DEAE-cellulose or Sephadex chromatography and were deemed proteins, based on their sensitivity to trypsin digestion. The inhibitory fractions eluted from DEAE-cellulose columns prior to the Ca2+-dependent activator protein. The inhibitory factors, unlike the activator protein, were stable to heat treatment under alkaline conditions. The inhibitory factors caused both an increase in Km for cyclic GMP and a decrease in V. In the presence of calcium ions and purified activator protein, the Ca2+-dependent phosphodiesterase was not inhibited by the factors, but instead was slightly stimulated. The inhibitory factors caused a slight apparent stimulation of a Ca2+-independent phosphodiesterase from rat cerebrum but this proved instead to be a nonspecific stabilizing effect which was minimicked by bovine serum albumin. After prolonged alkaline treatment, the purified activator protein caused a modest Ca2+-independent activation of Ca2+-dependent phosphodiesterase. The inhibitory factors antagonized the activation of Ca2+-dependent phosphodiesterase by alkaline treated activator protein or by lysophosphatidylcholine. The inhibitory factors had no effect on activity of trypsinized Ca2+-dependent phosphodiesterase. Of various other proteins, only casein mimicked the effects of the inhibitory factors on phoshodiesterase activity.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1979

Synthesis and biological properties of 2-, 5-, and 6-fluoronorepinephrines.

2-Fluoro-, 5-fluoro- and 6-fluorodimethoxybenzaldehydes were prepared by photochemical decomposition of the corresponding diazonium fluoroborates. The aldehydes were converted to the cyanohydrin trimethylsilyl ethers, which, in turn, were reduced to the dimethoxyphenethanolamines. Boron tribromide demethylation afforded the racemic ring-fluorinated norepinephrines. An alternate route, using the dibenzyloxyfluoroaldehyde, was also used to prepare 6-fluoronorepinephrine. The fluorine substituent markedly increases the phenolic acidities of these analogues. The biological properties conferred upon norepinephrine by the fluorine substituents in peripheral and central adrenergically responsive systems clearly demonstrate that 2-fluoronorepinephrine is a nearly a pure beta-adrenergic agonist, while 6-fluoronorepinephrine is an alpha-adrenergic agonist. 5-Fluoronorepinephrine retains both beta- and alpha-adrenergic agonist properties. Receptor-binding studies with specific radiolabeled ligands indicate that the specificity conferred by the site of fluorine substituents results from a change in the affinity of these analogues for the alpha- and beta-adrenergic receptors.

Animals↗
PubMed1977

N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor.

The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine.

Adenylyl Cyclases↗
PubMed1977

Effect of 2-fluorohistidine upon leukocytopoiesis in mice.

Administrationof L-2-fluorohistidine to mice produces a dose and time dependent leukopenia, hypocellularity with reduction in hematopoiesis in the spleen and bone marrow, and depletion of lymphocytes in the spleen, lymph nodes and cortex of the thymus. The LD50 is 250 mg/kg at five days. The effect on hematopoetic tissue is nearly as great at non-leathal "therapeutic" doses. Effects on circulating erythrocyte and reticulocyte levels and the deposition of hemosiderin in the spleen are minimal. At non-leathal doses the effects of this amino acid analog appear to be completely reversible after 6 to 10 days.A description of the toxicity, histopathology and a discussion of the possible mechanisms of action are presented.

Animals↗