Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Captopril, competitive inhibitor of angiotensin converting enzyme, is clinically employed for its antihypertensive activity and drug-dependent granulocytopenia or agranulocytosis have been seldom observed during treatment. In previous unpublished studies an activating effect of the drug on the complement alternate pathway has been demonstrated. In this paper we demonstrate that captopril-treated serum is able to "in vitro" induce granulocyte activation and aggregation. Granulocyte aggregation was shown by the turbidimetric method and cellular activation was confirmed by the release of the granule associated enzyme lysozyme and beta-glucuronidase. On this basis complement-mediated leukoaggregation and leukosequestration in vivo could be proposed as the effector mechanism of peripheral leukopenia.
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PMID:Captopril-induced granulocyte aggregation. A possible complement mediated mechanism of peripheral leukopenia. 676 21

Low-molecular-weight proteins (LMWPs) accumulate in the proximal tubular cells of the kidney, which makes these proteins interesting tools for renal drug targeting. We studied this approach using the LMWP lysozyme as a carrier for the angiotensin-converting enzyme inhibitor captopril. Captopril was conjugated to lysozyme via a disulfide bond. The pharmacokinetics of the captopril-lysozyme conjugate was studied in the rat. Only intact conjugate could be detected in the circulation. The total amount of captopril disulfides in the kidney was six times higher after administration of the conjugate than after the administration of an equivalent amount of free captopril. The conjugate was recovered in the urine partially as intact conjugate and partially as low-molecular-weight disulfides. The excretion of conjugate in the urine was not a consequence of the coupling of captopril to lysozyme because an equivalent bolus dose of native lysozyme was similarly excreted into the urine. By determination of the renal angiotensin-converting enzyme activity, we showed that the conjugate was degraded to the pharmacologically active captopril in vivo. We conclude that the coupling of captopril to the LMWP lysozyme results in increased captopril concentrations in the kidney and reduced captopril concentrations in the circulation.
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PMID:Specific delivery of captopril to the kidney with the prodrug captopril-lysozyme. 986 82

Nasal allergy is the most common type I allergic disease. During allergic reaction, chemical mediators may be released from residual cell, and thus, attract additional inflammatory cells. One mediator implicated in this response is bradykinin (BK), a potent proinflammatory nonapeptide. This study was designed to investigate the effects of BK on nasal mucosa, and to determine the role of angiotensin-converting enzyme (ACE) in BK-induced nasal responses. BK nasal provocation (100 micrograms) was studied in 7 normal volunteers and 7 patients with perennial allergic rhinitis. After provoking of BK response, nasal secretions and saline lavage fluids were collected for analysis of total protein (a protein secretion marker), albumin (a vascular permeability marker), and lysozyme (a serous cell marker). In addition, after administering of Captopril 50 mg, a specific ACE inhibitor, the same protocol was performed. In both groups, BK induced plasma exudation and serous gland secretion. Premedication with captopril did not alter BK-induced responses in normal individuals. In allergic patients, captopril enhanced BK-induced vascular permeability, but not glandular secretion. These results indicate that allergic subjects have nasal hyperresponsiveness to BK, and that ACE predominantly modulates the vascular permeability of allergic nasal mucosa. It seems likely that BK may contribute to the expression of nasal allergic symptoms, and that inhibition of ACE may lead to increased nasal responsiveness.
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PMID:[Role of angiotensin-converting enzyme on bradykinin nasal provocation: comparison of normal volunteers and allergic subjects]. 1019 23

We have synthesized a prodrug of the angiotensin-converting enzyme (ACE) inhibitor captopril by coupling this drug covalently to the low molecular weight protein (LMWP) lysozyme. Such drug-LMWP conjugates can be used for renal drug delivery, since LMWPs accumulate specifically in the proximal tubular cells of the kidney. In the present study, we compared the effects of captopril-lysozyme and free captopril in male Wistar rats. ACE activity in plasma and the kidney was measured after intravenous bolus injection of either the captopril-lysozyme conjugate (33 mg. kg(-1), corresponding to 0.2 mg. kg(-1) captopril) or equivalent dosages of free captopril and lysozyme. The administration of the captopril-lysozyme conjugate resulted in less plasma ACE inhibition and a longer-lasting renal ACE inhibition compared with the free drug. Effects on blood pressure and natriuresis were studied during intravenous infusion of captopril-lysozyme (275 mg. kg(-1). 6 h(-1) conjugate, corresponding to 5 mg. kg(-1). 6 h(-1) captopril) or an equimolar dosage of free captopril. Captopril-lysozyme did not affect systemic blood pressure, whereas free captopril lowered blood pressure significantly (-23 +/- 32% versus control after 6 h). Captopril-lysozyme increased natriuresis about 3-fold compared with control levels (260 +/- 32% after 6 h), whereas free captopril treatment resulted in a reduced sodium excretion (26 +/- 12%). Furthermore, captopril at a lower dose, which only moderately lowered blood pressure, showed an increased sodium excretion. We conclude that renal delivery of captopril using captopril-lysozyme results in reduced systemic activity and increased kidney-specific activity of the targeted drug.
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PMID:Targeting of captopril to the kidney reduces renal angiotensin-converting enzyme activity without affecting systemic blood pressure. 1202 48