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Biomedical subjects

M Donowitz

Publications and source records attributed to M Donowitz.

At least 145 records · Page 8Linked to original sources
PubMed1983

Neural control of acid-induced serotonin release from rabbit duodenum.

The neural mediation of acid-stimulated serotonin release was studied in isolated sheets of rabbit duodenal mucosa mounted in Ussing chambers. The serosal side of the mucosa was exposed to Ringer-HCO3 at pH 7.4, and the mucosal side was exposed to citrate-phosphate buffer at pH 3-6.8. Immunoreactive serotonin release occurred onto the luminal surface at pH 6 and below and onto the serosal surface at pH 5 and below, but was greater on the luminal side at each pH. The effect of cholinergic and adrenergic agonists and antagonists on mucosal serotonin release was measured at luminal pH 7.4, 5, and 4. Acid-stimulated luminal release was significantly inhibited by atropine, hexamethonium, and propranolol at pH 4 and 5 but not by phentolamine. Serotonin release was stimulated at pH 7.4 and 4 by carbachol and isoproterenol but not by norepinephrine or nicotine at pH 7.4. It is concluded that acid-induced and nonacid-induced mucosal serotonin release is partly neurally mediated by muscarinic cholinergic and beta-adrenergic mechanisms.

Animals↗
PubMed1983

Effect of dopamine and bromocriptine on rat ileal and colonic transport. Stimulation of absorption and reversal of cholera toxin-induced secretion.

Water and electrolyte transport were determined in rat ileum and colon using the single-pass perfusion technique. Intraperitoneal dopamine caused prompt stimulation of both ileal and colonic water absorption. The dopamine effect was mediated by both specific dopamine and alpha 2-adrenergic receptors. Haloperidol, a specific dopamine antagonist, and yohimbine, an alpha 2-adrenergic antagonist, inhibited the effect of dopamine in ileal absorption; both antagonists alone had no effect on basal water transport. Bromocriptine (intravenous and intraluminal) stimulated ileal and colonic water absorption, which was inhibited by haloperidol and yohimbine, and reversed cholera toxin-induced ileal secretion. Magnitude and time-courses of the increased water absorption in ileal loops, inoculated with saline, were the same as in loops, inoculated with saline, suggesting that bromocriptine acted to reverse cholera toxin-induced secretion by stimulating absorption. Bromocriptine had no effect on the cyclic adenosine monophosphate increase caused by cholera toxin. We conclude (a) dopamine stimulates water absorption in vivo in rat ileum and colon; (b) this dopamine effect is via specific dopamine and alpha 2-receptors; (c) bromocriptine stimulates water absorption in ileum and colon and also acts by dopamine and alpha 2-receptors; and (d) bromocriptine reverses cholera toxin-induced secretion.

Animals↗
PubMed1983

Pathophysiological mechanisms of diarrhoeal diseases: diverse aetiologies and common mechanisms.

A detailed review of the pathophysiology of diarrhoeal diseases is presented. Recent developments in the understanding of the mechanisms by which water absorption occurs via electrolyte transport are detailed. The secretion of Cl across the apical membrane in vivo is accompanied by a flow of Na as a counter ion, probably via the paracellular pathway. Normal regulation of active intestinal ion transport depends on cyclic AMP and cyclic GMP as well as intracellular calcium. In diarrhoeal diseases, some portion of the gut is usually found to be in a secretory rather than absorptive condition. This may be due to changes in active ion transport (decrease in Na absorption or increase in Cl secretion), alterations in intestinal motility and/or luminal osmolarity or to an increase in tissue hydrostatic pressure.

Calcium↗
PubMed1982

Ca2+- and calmodulin-dependent protein phosphorylation in rat lacrimal gland.

Ca2+, in homogenized lacrimal glands, enhanced phosphorylation of several peptides. Phosphorylation of two of these peptides was further stimulated by addition of the Ca2+-binding protein calmodulin and decreased by trifluoperazine, an inhibitor of Ca2+--calmodulin-dependent activity. Thus, Ca2+--calmodulin-dependent protein kinases and their substrates are present in lacrimal gland and could have an important role in lacrimal-gland function.

Animals↗
PubMed1982

Elevated intraluminal pressure alters rabbit small intestinal transport in vivo.

The effect of acutely increased intraluminal hydrostatic pressure (IHP) on rabbit jejunal, ileal, and colonic water and electrolyte transport was determined in vivo in a distended test segment and adjacent control segment using a perfusion system with [14C]polyethylene glycol as a nonabsorbable marker. Test-segment IHP was increased by raising the efflux catheter to produce 10-70 cm water IHP, while control-segment IHP was held constant at 0 cm water. Acutely increased IHP up to 40 cm water in the jejunum and up to 30 cm water in the ileum caused decreased net absorption in the jejunum and net secretion in the ileum but caused no significant change in control-segment transport. This indicated that IHP-induced changes in transport were mediated by local rather than systemic effects. The IHP-induced secretory process was dependent on the magnitude of elevation in IHP and reversible at less than or equal to 20 cm water in the ileum. An IHP of 30 cm water was associated with nonreversible transport changes in the ileum. Acutely increased IHP to 70 cm water did not significantly alter colonic transport. This experimental model is suitable for a comprehensive investigation of the mechanism of IHP-induced changes in small intestinal transport.

Animals↗
PubMed1982

Intestinal filtration-secretion due to increased intraluminal pressure in rabbits.

The mechanism of changes in small intestinal transport due to acutely increased intraluminal hydrostatic pressure (IHP) was investigated in detail using perfused in vivo rabbit intestinal segments. IHP affected passive transport in vivo by increasing effective mucosal surface area in the small intestine (indicated by 3HOH transport and tissue architectural changes) and increasing small intestinal permeability (indicated by a proportionately greater increase in mannitol than erythritol secretory clearance). IHP did not alter ileal blood flow rate measured by radioactive microspheres, despite grossly evident venous dilatation, or active intestinal transport in the ileum as measured by a) in vitro ion transport in the absence of elevated hydrostatic pressure, b) mucosal adenylate cyclase or Na-K-ATPase activities, and c) glucose-stimulated water and electrolyte absorption. Acutely increased IHP appears to influence the hydrodynamics of the mucosal microcirculation in the rabbit ileum to produce a driving force for passive filtration-secretion, which is associated with and possibly augmented by increased tissue permeability and effective surface area.

Animals↗
PubMed1982

Effect of cycloheximide on corticosteroid-induced changes in colonic function.

Chronic parenteral mineralocorticoid and glucocorticoid treatment increases colonic sodium and water absorption and mucosal Na-K-ATPase activity. Cycloheximide, a protein synthesis inhibitor, was utilized to compare the mechanisms of action of these corticosteroids. Rats were injected with 50 or 100 micrograms/100 g body wet cycloheximide every 12 h, 0.5 or 3 mg/100 g deoxycorticosterone (DOCA) daily, or 3 mg/100 g methylprednisolone (MP) daily, singly or in combination for 2 days. In water absorption, transmural potential difference, and the specific activity of Na-K-ATPase were measured. Cycloheximide alone did not alter colonic water, sodium, or chloride absorption or Na-K-ATPase activity but did increase transmural potential difference. DOCA-induced increases in colonic absorption and Na-K-ATPase were completely prevented by cycloheximide. Cycloheximide completely prevented the increase in Na-K-ATPase in MP-treated rats but only partially reduced the MP-induced increase in sodium and water absorption. These results suggest that this enzyme is not the primary site of glucocorticoid action. It remains to be determined whether an increase in Na-K-ATPase activity is a necessary part of the maximal colonic response to chronic glucocorticoid treatment.

Absorption↗
PubMed1982

Chloroquine stimulates absorption and inhibits secretion of ileal water and electrolytes.

The effects of chloroquine diphosphate, a drug with "'membrane-stabilizing" properties, were studied on basal ileal absorption and on ileal secretion induced by increased intracellular cAMP levels and calcium (serotonin). The studies were performed on rat (in vivo) and rabbit ileum (in vitro). Intraluminal chloroquine (10(-4) M) reversed cholera toxin- and theophylline-induced secretion in rat ileum but did not alter the cholera toxin- and theophylline-induced increases in cAMP content. Addition of chloroquine (10(-4) M) to the mucosal surface of rabbit ileum did not alter basal active electrolyte transport or the serotonin-induced decreased Na and Cl absorption but inhibited the theophylline-induced C1 secretion. Addition of chloroquine (10(-4)) M) to the serosal surface stimulated net Na and Cl absorption. This effect may involve intracellular calcium. Chloroquine increased the rabbit ileal calcium content and decreased 45Ca2+ influx from the serosal surface. Both the mucosal and serosal effects of chloroquine described led to a net increase in absorptive function of the intestine and should prove useful in developing treatment of diarrheal diseases.

Absorption↗
PubMed1982

Dopamine stimulation of active Na and Cl absorption in rabbit ileum: interaction with alpha 2-adrenergic and specific dopamine receptors.

The effects of dopamine on active intestinal ion transport have been evaluated. An epithelial sheet preparation of rabbit ileum was used in vitro with the Ussing chamber-voltage clamp technique. Dopamine, in the presence of 1 mM ascorbic acid, added to the serosal bathing solution caused a dose-dependent decrease in short-circuit current, with a half-maximal effect at 1.2 muM and maximal effect of -50 muA/cm(2) at 50 muM; dopamine decreased the potential difference, and increased the conductance and net Na and net Cl absorption. There was no effect on the residual ion flux. Dopamine did not alter the change in short-circuit current caused by mucosal glucose (10 mM) or serosal theophylline (10 mM). Mucosal dopamine had no effect. The effect of dopamine on short-circuit current was inhibited by the dopamine antagonists haloperidol and domperidone and the alpha(2)-adrenergic antagonist yohimbine; there was no effect of the alpha(1)-antagonist prazosin and the beta-antagonist propranolol. In addition, the alpha(2)-adrenergic agonist clonidine, but not the alpha(1)-agonist methoxamine caused a dose-dependent decrease in short-circuit current. The ileal effects of dopamine did not occur via conversion into norepinephrine or release of norepinephrine from the peripheral nerves since "peripheral sympathectomy" with 6-hydroxydopamine did not alter the dopamine-induced change in ileal short-circuit current. The dopamine effects were not associated with a change in basal ileal cyclic AMP content but were associated with a decrease in total ileal calcium content as measured by atomic absorption spectrometry and as estimated by (45)Ca(++) uptake. The decrease in calcium content could be attributed to a dopamine-induced decrease in (45)Ca(++) influx from the serosal surface. Because of the presence of dopamine in ileal mucosa and these effects on ileal electrolyte transport, it is possible that dopamine may be involved in the physiologic regulation of active intestinal electrolyte absorption.

Animals↗
PubMed1982

Evaluation for colon cancer in patients with occult fecal blood loss while taking aspirin: a Bayesian viewpoint.

This paper examines the implications of occult fecal blood loss in patients taking aspirin (at least 2 grams daily). Although such patients do have a somewhat higher probability of colonic carcinoma than do members of the general population, their risk is far lower than that of patients who have gastrointestinal blood loss when not taking aspirin. This difference in risk exists because aspirin itself can provoke occult blood loss in stool. Patients who manifest gastrointestinal blood loss while taking aspirin can be separated into two groups, based on whether or not that blood loss continues after aspirin is discontinued. Although patients who continue to bleed are at high risk for colonic carcinoma, those who cease having any blood loss are at lower risk than are members of the general population. Further diagnostic studies to detect colonic carcinoma should be pursued in the former group, but not in the latter, low-risk group.

Adult↗
PubMed1981

Reversible sulfasalazine-induced granulomatous hepatitis.

Sulfasalazine, a drug common in the treatment of inflammatory bowel disease, may cause liver damage. We present a patient with documented granulomatous hepatitis which resolved on liver biopsy 6 weeks after discontinuation of the drug.

Adult↗
PubMed1981

Effects of methylprednisolone on electrolyte transport by in vitro rat ileum.

Administration of the glucocorticoid methylprednisolone (MP) (30 mg/kg body wt for 3 days) to rats increased intestinal mucosal guanylate cyclase and Na-K-ATPase activities, short-circuit current (Isc), electrical potential difference (PD), net Na absorption, and net Cl secretion and reversed HCO3 transport from secretion to absorption. In the MP-treated animals, removal of HCO3 from both the mucosal and serosal bathing solutions increased Cl secretion but did not alter the Isc, PD, and net Na flux. Removal of Cl abolished the MP-induced increase in Isc but did not affect the MP-induced changes in net Na and HCO3 fluxes. At 6 h, after a single dose of MP, stimulation of guanylate cyclase activity was already maximal, whereas Na-K-ATPase activity was not detectably altered. The changes in intestinal transport properties present 6 h after MP treatment and associated with the increased guanylate cyclase activity were an increase in Isc and PD and a reversal of net Cl absorption to net secretion. These results suggest that an initial response to MP administration is a persistent increase in intestinal guanylate cyclase activity that mediates an electrogenic Cl secretory process, then is followed by a superimposed effect of increased Na-K-ATPase activity that mediates an increase in net Na absorption.

Animals↗
PubMed1981

Effects of spironolactone and amiloride on corticosteroid-induced changes in colonic function.

Mineralocorticoid and glucocorticoid effects on colonic electrolyte absorption were compared by examining the alterations caused by spironolactone and amiloride in corticosteroid-treated rats. Animals were treated for 3 days with deoxycorticosterone acetate (DOCA; 0.5 mg . 100 g-1 . day-1), methylprednisolone (MP; 3 or 0.5 mg . 100 g-1 . day), and spironolactone (14 mg . 100 g-1 . day-1 im) singly or in combination. On day 4, rats were anesthetized with pentobarbital sodium and perfused in vivo with Ringer-HCO3 solution. Both doses of MP and DOCA increased net colonic sodium and water absorption and mucosal Na-K-ATPase activity. Concurrent spironolactone treatment completely prevented these effects in DOCA-treated rats but had no effect in MP-treated rats. Untreated, MP-treated, and DOCA-treated animals were perfused with a Ringer-HCO3 solution containing 1 mM amiloride. Amiloride reduced net colonic sodium and water absorption, transmural potential difference, and potassium secretion in all rats by approximately 55%. These effects were almost immediate and completely reversible. These findings in the rat suggest that 1) different receptors mediate the colonic effects of mineralocorticoids and glucocorticoids and 2) these corticosteroids do not differ in their relative effects on amiloride-sensitive and amiloride-resistant colonic sodium transport processes.

Adrenal Cortex Hormones↗