Publications by authors named "Schlondorff D"

Massive secretory diarrhea is associated with some villous adenomas. The mechanism of this secretion is unknown but the character of the diarrhea resembles that of cyclic nucleotide-mediated diarrheas. We have compared the cyclic nucleotide metabolism of a large secretory villous adenoma with a nonsecretory villous adenoma, a solid carcinoma and their normal mucosae.

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Because there is an accumulation of macrophages in the Bowman's space during human and experimental glomerulonephritis, we have studied the binding of [3H]-uridine labeled macrophages to isolated glomeruli. Binding was related to the glomerular protein and macrophage concentrations, temperature, time of incubation, and was a saturable process. Macrophage adherence depended on glomerular lipoxygenase activity but not on glomerular cyclooxygenase activity since preincubation of glomeruli with nordihydroguaiaretic acid (NDGA) inhibited this phenomenon whereas preincubation with indomethacin was ineffective.

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Prostaglandin (PG) inhibits the hydroosmotic effect of vasopressin. We therefore reexamined the interaction of vasopressin (VP), cAMP, and prostaglandins in toad bladder epithelial cells. Vasopressin slightly, but reproducibly, stimulated PGE2 and thromboxane B2 (TXB2) synthesis in cells prepared by the use of collagenase.

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We examined the influence of angiotensin II (ANG II), arginine vasopressin (AVP), and platelet activating factor (PAF) on prostaglandin (PG) synthesis and cell contractility in human glomerular mesangial cells in culture. Addition of sodium butyrate to the culture medium for 40 h significantly increased synthesis of both 6-keto-PGF1 alpha and PGE2 in the presence of exogenous arachidonic acid and of PGE2 under basal conditions. To optimize conditions in all further experiments, cells cultured with butyrate were studied.

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Prostaglandin E2 (PGE2) inhibits the action of the antidiuretic hormone (ADH) in isolated collecting tubules. A negative feedback loop has been postulated whereby ADH stimulates PGE2 synthesis. Furthermore, lysyl-bradykinin (LBK) inhibits the antidiuretic effect of ADH, probably via PGE2.

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The mechanism of arachidonic acid release and prostaglandin E2 (PGE2) synthesis was studied in cultured mesangial cells from rat kidneys. Both the ionophore A23187 and angiotensin II stimulated radioimmunoassayable PGE2 synthesis. The effect of angiotensin occurred within minutes, with half-maximal stimulation around 10(-9) M.

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Prostaglandins produced by the glomerulus are important factors in controlling glomerular function. The controlling step, i.e.

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The interaction of inflammatory cells and glomerular prostaglandins (PG) may be important during glomerulonephritis. We therefore examined the influence of platelet-activating factor (PAF), (a mediator of inflammation released from leukocytes) and of phagocytosis of zymosan on arachidonic acid metabolism and on cell contractility in rat glomerular mesangial cells in culture. PAF increased PGE2 synthesis (determined by radioimmunoassay) within minutes (threshold: 10(-10)M; maximal effect: 10(-7)M).

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The interaction of proliferating macrophages with the glomerulus may play an important role in certain forms of glomerulonephritis. This interaction could involve metabolites of arachidonic acid (C20:4) such as prostaglandins (PG) and lipoxygenase products. We therefore investigated the conversion of exogenous [3H] C20:4 into hydroxyeicosatetraenoic acids (HETE) and PG by isolated glomeruli and macrophages from rats, alone and in combination.

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Obstructive uropathy is associated with changes in several renal functions. As some of these are mediated by cAMP, we examined whether changes in cAMP metabolism could contribute to the pathophysiology of unilateral ureteral ligation in rats. We found that basal adenylate cyclase in the cortex of the obstructed kidney doubled after 3-7 days, but the response to NaF and parathyroid hormone was decreased.

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A role for transmembrane calcium movement in vasopressin stimulation of its target cell has been postulated based on studies with calcium entry blockers such as verapamil. We examined the effect of three sets of structurally different calcium blockers--D600 (an analogue of verapamil), diltiazem, and nifedipine--on water flow in toad bladder. D600 (200 microM), diltiazem (200 microM), and nifedipine (60 microM) inhibited vasopressin-induced water flow but enhanced adenosine 3',5'-cyclic monophosphate (cAMP)-induced water flow, suggesting that the drugs inhibit cAMP generation in response to vasopressin but enhance the response to exogenous cAMP by inhibiting phosphodiesterase activity.

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In addition to their effect on angiotensin and bradykinin metabolism, converting enzyme inhibitors (CEI) may also alter prostaglandin (PG) synthesis. We therefore examined two CEI, SQ 14,225 (captopril) and SQ 20,881, for their in vitro effect on PG synthesis by glomeruli and aortic strips from rats. Glomeruli incubated in test tubes produced predominantly PGE2 and PGF2 alpha.

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The interaction of vasopressin with prostaglandins were examined in the toad bladder by determining water flows, cAMP levels, and cAMP-dependent protein kinase activity. Both water flow and activation of cAMP-kinase in response to vasopressin were enhanced after prostaglandin inhibition, consistent with inhibition of vasopressin-induced cAMP generation by endogenous prostaglandins. On the other hand exogeneous PGE stimulated cAMP generation.

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There is evidence that prostaglandins modulate renal hemodynamics in unilateral ureteral obstruction. We examined prostaglandin synthesis by glomeruli from rats with 24- and 72-h unilateral ureteral ligation. During prelabeling of the lipid pools with [14C]arachidonate glomeruli from the ligated kidney incorporated less 14C label than those from contralateral or normal control kidneys.

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We noted five cases of reversible acute deterioration of renal function in patients with very mild to moderate renal insufficiency who received indomethacin for an acute gouty attack. This decrease in renal function was consistent with a primary decrease in renal blood flow. In addition, hyperkalemia developed in the patients, which we attribute to a decrease in renin and aldosterone secretion, a decrease in distal tubular delivery of sodium, and, more importantly, to a decrease in urine flow.

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The effect of acute infusion of the prostaglandin synthetase inhibitors - meclofenamate or indomethacin - was examined in awake rats. Studies were performed in normal rats undergoing either sodium or water diuresis and in salt-replete rats with chronic renal insufficiency. Prostaglandin synthetase inhibitors had no effect on renal plasma flow, glomerular filtration rate or fractional excretion of sodium in any of the groups.

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Calcium ion plays a major regulatory role in many hormone-stimulated systems. To determine the site of calcium's action in the toad urinary bladder, we examined the effect of trifluoperazine, a compound that binds specifically to the calcium binding protein, calmodulin, and thereby prevents activation of enzymes by the calcium- calmodulin complex. 10 microM trifluoperazine inhibited vasopressin stimulation of water flow, but did not alter vasopressin's effects on urea permeability or short-circuit current.

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Amrinone is a new noncatechol, nonglycoside agent with cardiotonic and vasodilator properties. This paper examines the effects of amrinone in the toad urinary bladder, a tissue whose function may be altered by many factors which also change cardiovascular activity. Amrinone enhanced the effect of vasopressin and cyclic AMP on water and urea permeabilities, as well as the effect of vasopressin on sodium transport.

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Prostaglandins are important modulators of the action of vasopressin. Others researchers have proposed that vasopressin stimulates prostaglandin synthesis, completing a negative feedback loop and thereby limiting vasopressin's antidiuretic effect. We have re-examined this question, using specific radioimmunoassay and thin-layer radiochromatography to determine prostaglandin synthesis by the toad bladder.

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Prostaglandins play a role in the regulation of renal blood flow and glomerular filtration. In the presence of [14C]arachidonate the pattern of prostaglandins produced by isolated glomeruli was PGF2 alpha > PGE2 > PGD2 = TXB2 = 6-keto-PGF1 alpha (a metabolite of prostacyclin). Glomeruli prelabeled with [14C]arachidonate showed an additional labeled prostaglandin that co-chromatographs with 6,15-diketo-13,13-dihydro-PGF1 alpha and may represent breakdown product of prostacyclin.

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