Response of Plasma Histaminase Activity to Small Doses of Heparin in Normal Subjects and Patients with Hyperlipoproteinemia

115

A B S T R A C T Diamine oxidase (DAO; EC 1.4.3.6) is an enzyme found in high activity in the mature cells of the upper villus of rat small intestinal mucosa and in very much lower activity in all other tissues in the nonpregnant rat. This study was designed to determine whether a provocative test for increasing the level of plasma DAO activity by heparin administration could be used to monitor the extent and severity of acute, severe, small intestinal mucosal injury. In adult rats, small intestinal loops of varying lengths were perfused with 2,100 mosM sodium sulfate solution for 60 min to produce selective damage to villus epithelium. Plasma postheparin DAO (PHD) activity (180 min after 400 U/kg i.p. heparin) was measured 7 h after initiation of perfusion. With increasing length of intestinal mucosal injury, there was a progressive decrease in both basal and plasma PHD activity. The decrease in plasma PHD activity closely reflected the length of intestinal mucosa injured (n = 128, r = 0.86, P < 0.001), and it was much more sensitive (threshold limit of detection = 13% of total length, range = 67 U/ml for 100% length of injury) than unstimulated basal levels of plasma DAO (threshold = 40%, range = 2.1 U/ml). Our previous data have suggested that DAO is unique among intestinal mucosal enzymes in that circulating levels can serve as a marker of mucosal injury; this study illustrates that the addition of a lowdose heparin administration enhances the use of DAO even further as a sensitive, quantitative, circulating marker for monitoring the extent of small intestinal mucosal injury in the rat.Dr.

Section: Discussionsupporting

confidence: 93%

“…Heparin administration is known to increase plasma DAO activity in man and other mammalian species (11,(15)(16)(17)(18). Several studies suggest that the source of this plasma postheparin DAO (PHD) in the rat is the intestine (11,19,20).…”

Section: Introductionmentioning

confidence: 99%

Plasma postheparin diamine oxidase. Sensitive provocative test for quantitating length of acute intestinal mucosal injury in the rat.

Luk

Bayless²,

Baylin³

1983

115

“…DAO activity is produced in particularly high amounts by the maternal placenta (5,6), and this results in large increases in enzyme activity in plasma (e.g., [7][8][9][10][11] (unpublished data) during pregnancy. In nonpregnant animals, the enzyme is released upon injection of heparin into the circulation of humans (12)(13)(14) and the rat, rabbit (15), and guinea pig (15,16). Inasmuch as this release is apparent within 20 s (14) and because DAO activity is present in or on microvascular endothelial cells from rat and guinea pig (17), we have examined the possibility that heparin might act by displacement of DAO from vascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

“…In nonpregnant animals, the enzyme is released upon injection of heparin into the circulation of humans (12)(13)(14) and the rat, rabbit (15), and guinea pig (15,16). Inasmuch as this release is apparent within 20 s (14) and because DAO activity is present in or on microvascular endothelial cells from rat and guinea pig (17), we have examined the possibility that heparin might act by displacement of DAO from vascular endothelial cells. By analogy, lipoprotein lipase (LPL) activity (EC 3.1.1.3) is released along with DAO activity into the circulation by heparin (13,14), is bound to cultured endothelial cells from bovine pulmonary artery (18) and calf aorta (19), and is displaced from these cells by heparin from sites believed to contain heparan sulfate-like moieties (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Binding of diamine oxidase activity to rat and guinea pig microvascular endothelial cells. Comparisons with lipoprotein lipase binding.

Robinson‐White¹,

Baylin²,

Olivecrona³

et al. 1985

Microvascular endothelial cells from rat and guinea pig fat pads were shown to bind diamine oxidase (DAO) activity when incubated with soluble extracts of placenta (33 DAO U/mg of placenta) and a purified placental enzyme preparation (94 U/ gg of protein). The extent of binding was dependent on the concentration of enzyme activity and tissue. Saturation of binding sites with 5,000 U of DAO/ml resulted in levels of bound activity (up to 11-13 U/mg of endothelial cells) in excess of that observed in all tissues except placenta. Scatchard plots suggested that there were at least two DAO binding sites (apparent K., 92 and 2,450 U/ml). Although the same cell preparations bound 125I-labeled lipoprotein lipase (LPL), the presence of LPL on the endothelial cell surface did not interfere with the binding of DAO activity except when cells were exposed to high concentrations of LPL. Alternatively, bound DAO activity was partially displaced (up to 33%) only with high concentrations (30 zg/ml) of LPL. DAO activity may thus be bound to at least two populations of sites, one of which may bind LPL. Both enzymes, however, were displaced by heparin (0.05-5 U/ml) and DAO binding was impaired by prior treatment of cells with proteolytic and glycosaminoglycandegrading enzymes. The demonstration of DAO binding to vascular endothelial cells provides a further example of the ability of these cells to bind enzymes at their surface and thereby act on biologically active substances in the circulation.

“…In the nonpregnant rat, the small intestine is the tissue containing the highest DAO activity, and the increase in circulating DAO that occurs following heparin administration appears to come primarily from the small intestine (8,9). In man, a similar rise in plasma DAO is seen after heparin infusion, and the small intestine is again the tissue containing the highest DAO activity (10,11). However, the potential value of DAO as an index of intestinal function has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity.

Luk¹,

Bayless²,

Baylin³

1980

233

158

A B S T R A C T Diamine oxidase (histaminase) is an enzyme founid in high concentrations in the intestinal mucosa of humans and other mammalian species. We investigate(l whether plasma and mucosal levels of diaminie oxidase activity reflect both the maturational status ofthe mucosa during its development in the newborn rat and the degree of mucosal damage during its injury in the adult rat. Litter mates were reared under identical conditions and killed at different ages from day 0 to day 40 after birth. Diamine oxidase in the small intestine was low at birth, increased gradually with age, reached a peak at 22 d, and then remained at normiial adult levels, similar to the developmental patterns of maltase and sucrase. Plasma diamine oxidase rose in parallel with intestinal levels (n = 500, r = 0.84, P < 0.001), reached a peak at 24 d, and then remiained at normal adult levels. Diamine oxidase activitv in 15 nonintestinal tissues was <5% of ileal mucosal activity, and no nonintestinal activities showed increase with age. Adult rat intestinal loops were perfused with hyperosmolar sodium sulfate solutions to procluce selective d(amage to villus mucosa. With increasing mucosal damage, there was a progressive decrease in the enzyme activities studied; first, lactase levels fell, then maltase and sucrase, and finally muciosal and plasma diamine oxidase activity levels fell. The decrease in plasma diamine oxidase reflected the degree of mucosal damage (n = 29, P < 0.04). Diamine oxidase activity is thus unique among intestinal mucosal enzymes studied to date in that circulating levels can serve as a marker of mucosal maturation and integrity.