Drugs online research references
Theriogenology. 1998 Sep;50(4):651-7.
Effect of kininase II inhibitors on bradykinin-stimulated bovine sperm motility.
Somlev B, Subev M.
Institute of Biology and Immunology of Reproduction, Sofia, Bulgaria.
It has been found that the enzyme kininase II present in the seminal plasma inactivates the kinins produced by the kallikreins, thus blocking their beneficial effects on the motility of post-ejaculated mammalian spermatozoa. In this study we examined the influence of 2 kininase II inhibitors (captopril and enalapril maleate) on bradykinin-induced bovine sperm motility. Ejaculates were collected from Holstein-Friesian bulls, and semen samples exhibiting reduced sperm motility (30 to 60%; mean 53 +/- 3.8%) were used. Each semen sample was divided into 6 portions: 1) control; 2) treated with bradykinin (M-8); 3) treated with captopril (M-2); 4) treated with enalapril maleate (M-3); 5) treated with bradykinin + captopril; and 6) treated with bradykinin + enalapril maleate. Total sperm motility was recorded over 4 h at 1-h intervals. It was found that in the second hour after treatment both the combinations of bradykinin + captopril and bradykinin + enalapril maleate considerably enhanced sperm motility compared with that of the controls (P < 0.01 and P < 0.05, respectively). Total sperm motility rates of semen samples treated with these combinations were also higher than in the samples treated either with inhibitors alone or with bradykinin alone. We concluded that the stimulatory effect of bradykinin on bovine sperm motility was considerably potentiated and prolonged by the addition of the kininase II inhibitors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10732155&dopt=Abstract
Res Commun Mol Pathol Pharmacol. 1999;104(3):345-60.
Inhibition of calcium ionophore-stimulated leukotriene generation from intact human neutrophils by captopril.
Mansour M, Agha A.
Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Effects of captopril on the formation of leukotrienes (LTs) from stimulated intact human neutrophils were investigated. Neutrophils were stimulated with 1 microM calcium ionophore A23187 for the generation of LTs. A reverse phase high performance liquid chromatography technique and UV spectroscopy were used to detect and quantitate the released LTs namely, LTB4. LTC4. delta6-trans-LTB4 and delta6-trans-12-epi-LTB4. Preincubation of neutrophils with captopril significantly reduced LTB4 formation in a concentration-dependent manner, as compared to diluent-treated control cells. Since LTA4 is the substrate for both LTB4 and LTC4, thus in presence of captopril, shunting of LTA4 from synthesis of LTB4 was not directed to LTC4 formation. This finding was evidenced by the significant decrease of LTC4 production under the influence of high concentration of the drug. Formation of LTB4 stereoisomers, delta6-trans-LTB4 and delta6-trans-12-epi-LTB4 was not markedly altered by captopril. In subsequent experiments, when neutrophils were stimulated with A23187 after preincubation with exogenous arachidonic acid (75 microM), and treatment with captopril, similar findings were obtained for LTB4 and LTC4. Meanwhile, formation of the nonenzymatic hydrolysis products of LTA4 tended to rise reaching significant level in case of delta6-trans-LTB4, at the high concentration of captopril. These results demonstrate that captopril is an inhibitor of enzymatically generated LTs produced by intact human neutrophils, being more potent against LTB4. These effects of captopril on LTs are not mediated via an inhibition of arachidonic acid formation from membrane phospholipids. It could be suggested that captopril, at doses used clinically. could inhibit the generation of LTB4 without affecting LTC4. Consequently, these findings might account for possible antiinflammatory activity for captopril, and further suggest that some of the observed side effects of captopril might not be related to an overproduction of LTC4.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10741385&dopt=Abstract
Immunopharmacology. 2000 Mar;46(3):237-46.
Angiotensin converting-like enzymes from urine of untreated renovascular hypertensive and normal patients: purification and characterization.
Costa RH, Casarini DE, Plavnik FL, Marson O, Alves KB.
Department of Biochemistry, Universidade Federal de Sao Paulo-Escola Paulista de Medicina, SP, Brazil.
Angiotensin converting-like enzymes (ACE) were isolated from urine of normal (P0N, P1N and P2N) and untreated renovascular hypertensive (P0, P1 and P2) patients. The urine were submitted to ion exchange chromatography. Enzymes P0 and P0N were eluted with the equilibrium buffer (0.02 M Tris-HCl, pH 7.0), while P1, P1N, P2 and P2N with ionic strength linear gradient of 0.02-0.5 M Tris-HCl, pH 7.0 in 0.7 mS and P2 and P2N in 1.2 mS conductance. The active fractions were submitted to gel filtration in Sephadex G-150, equilibrated and performed with 0.05 M Tris-HCl/0.15 M NaCl buffer, pH 8.0. All enzymes were homogeneous when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (molecular mass: P0, P2 and P2N about 60 kDa; P1, 95 kDa and P21N 170 kDa). The enzymes were recognized by Y1 polyclonal antibody raised against human renal ACE. The K(M) values were in millimolar order for hippuryl-L-His-Leu (HHL) while for benzyloxycarbonyl-Phe-L-His-Leu (ZFHL) they were in 10(-4) M order. The enzymes were able to hydrolyze angiotensin I (AI) (P0 and P0N about 25%, P1 and P1N about 70%, P2 100% and P2N 66%) and bradykinin (BK) (P0N 22%, P1N 81%, P2N 62%, P0 and P1 50% and P2 35%), and their activities were inhibited by captopril.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10741903&dopt=Abstract
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