Methylprednisolone stimulation of guanylate cyclase activity in rat small intestinal mucosa: Possible role in electrolyte transport

Marnane, W. G.; Tai, Y. H.; Decker, R. A.; Boedeker, Edgar C.; Charney, Alan N.; Donowitz, Mark

doi:10.1016/0016-5085(81)90657-0

Cited by 15 publications

(2 citation statements)

References 37 publications

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“…5B). These findings are consistent with other reports of glucocorticoid-mediated stimulation of sGC activity in other types of tissue, such as rat glomeruli and small intestine mucosa (27,30).…”

Section: Discussionsupporting

confidence: 94%

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Perez

Lakshminrusimha

Wedgwood

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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In the pulmonary vasculature, cGMP levels are regulated by soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5). We previously reported that lambs with persistent pulmonary hypertension of the newborn (PPHN) demonstrate increased reactive oxygen species (ROS) and altered sGC and PDE5 activity, with resultant decreased cGMP. The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O(2) for 24 h. Six lambs received 5 mg/kg hydrocortisone every 8 h times three doses (PPHN-hiHC), five lambs received 3 mg/kg hydrocortisone followed by 1 mg·kg(-1)·dose(-1) times two doses (PPHN-loHC), and six lambs were ventilated with O(2) alone (PPHN). All groups were compared with healthy 1-day spontaneously breathing lambs (1DSB). O(2) ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved arterial-to-alveolar ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose hydrocortisone also increased sGC activity, decreased PDE5 expression, decreased ROS, and increased total vascular SOD activity vs. PPHN lambs. These data suggest that hydrocortisone treatment in clinically relevant doses improves oxygenation and decreases hyperoxia-induced changes in sGC and PDE5 activity, increasing cGMP levels. Hydrocortisone reduces ROS levels in part by increasing SOD activity in PPHN lambs ventilated with 100% O(2.) We speculate that hydrocortisone increases cGMP by direct effects on sGC and PDE5 expression and by attenuating abnormalities induced by oxidant stress.

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Section: Discussionsupporting

confidence: 94%

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Perez

Lakshminrusimha

Wedgwood

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Glucocorticoid hormones have been shown to influence the structure and/or function of a wide variety of cell types, including small-and large-intestinal epithelial cells (Charney et al, 1975;Ananna et al, 1979;Scott et al, 1981; Lentze et al, 1985;Dudeja et al, 1987). For example, these hormones have been shown to affect intestinal fluid, electrolyte and nutrient absorption (Charney et al, 1975;Binder, 1978;Field, 1978;Meneely & Ghishan, 1982; Dudeja et al, 1987), epithelial-cell maturation (Henning & Sims, 1979) and the activities of certain plasma-membrane-bound enzymes (Lebenthel et al, 1972;Daniels et al, 1973;Marnane et al, 1981). Recently, our laboratory has also demonstrated that administration of the synthetic glucocorticoid dexamethasone altered the glycosphingolipid composition of the rat proximal-small-intestinal mucosa as well as changing the lipid fluidity and phospholipid composition of rat small-and largeintestinal brush-border membranes (Brasitus et al, 1987b;Dudeja et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone influences the lipid fluidity, lipid composition and glycosphingolipid glycosyltransferase activities of rat proximal-small-intestinal Golgi membranes

Dudeja

Dahiya

Brown

et al. 1988

Biochemical Journal

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Experiments were performed to examine the effects of subcutaneous administration of the synthetic glucocorticoid dexamethasone (100 micrograms/day per 100 g body wt.) on the lipid fluidity, lipid composition and glycosphingolipid glycosyltransferase activities of rat proximal-small-intestinal Golgi membranes. After 4 days of treatment, Golgi membranes and liposomes prepared from treated rats were found to possess a greater fluidity than their control (diluent or 0.9% NaCl) counterpart, as assessed by steady-state fluorescence-polarization techniques using three different fluorophores. Moreover, analysis of the effects of temperature on the anisotropy values of 1,6-diphenylhexa-1,3,5-triene, using Arrhenius plots, demonstrated that the mean break-point temperatures of treated preparations were 4-5 degrees C lower than those of control preparations. Changes in the fatty acyl saturation index and double-bond index of treated membranes, secondary to alterations in stearic acid, linoleic acid and arachidonic acid, at least in part, appeared to be responsible for the differences in fluidity noted between treated and control Golgi membranes. Concomitant with these fluidity and lipid-compositional alterations, treated membranes possessed higher specific activities of UDP-galactosyl-lactosylceramide galactosyltransferase and CMP-N-acetylneuraminic acid:lactosylceramide sialyltransferase than their control counterparts. Experiments utilizing benzyl alcohol, a known fluidizer, furthermore suggested that the fluidity alteration induced by dexamethasone may be responsible for the increased activity of the former, but not the latter, glycosphingolipid glycosyltransferase.

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Ion and Water Transport in the Intestine

Powell¹

1986

Physiology of Membrane Disorders

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Methylprednisolone stimulation of guanylate cyclase activity in rat small intestinal mucosa: Possible role in electrolyte transport

Cited by 15 publications

References 37 publications

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Dexamethasone influences the lipid fluidity, lipid composition and glycosphingolipid glycosyltransferase activities of rat proximal-small-intestinal Golgi membranes

Ion and Water Transport in the Intestine

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