Drugs online research references









J Insect Physiol. 2000 Nov 1;46(11):1423-1431.
Effect of helicokinins and ACE inhibitors on water balance and development of Heliothis virescens larvae.

Seinsche A, Dyker H, Losel P, Backhaus D, Scherkenbeck J.

Central Research, Bayer AG, LWZ Monheim, Geb. 6220, Alfred-Nobel-Strasse 50, 40789, Monheim, Germany

The diuretic activity of the helicokinins I (YFSPWG-amide), II (VRFSPWG-amide) and III (KVKFSAWG-amide) was tested on Heliothis virescens larvae. All three kinins increased fluid secretion in isolated Malpighian tubules in a dose-dependent manner. Injections into the haemolymph caused a significant reduction in weight gain after 24 h and, in the case of helicokinin I, led to an increased mortality of 43% within 6 days. When truncated analogues of helicokinin I were tested in vitro, only the pentapeptide (FSPWG-amide) stimulated fluid secretion. Tested in vivo the pentapeptide did not influence normal development of the larvae. An alanine scan of helicokinin I showed that the substitution of phenylalanine, tryptophan and glycine led to a massive decrease or even loss of diuretic activity. The substitution of the other amino acids had no effect in vitro. The ACE inhibitors captopril, enalapril-maleate and lisinopril were tested for their influence on the development of the larvae. In combination with one of the helicokinins the in vivo injection of the ACE inhibitors led to increased rates of mortality and/or reductions in pupal weight.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10891570&dopt=Abstract [PubMed - as supplied by publisher]




Am J Physiol Lung Cell Mol Physiol. 2000 Jul;279(1):L143-51.
Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor.

Wang R, Ibarra-Sunga O, Verlinski L, Pick R, Uhal BD.

The Cardiovascular Institute and Division of Cardiology, Michael Reese Hospital, Chicago, Illinois 60616, USA.

Angiotensin-converting enzyme is involved in apoptosis of alveolar epithelial cells (Wang R, Zagariya A, Ang E, Ibarra-Sunga O, and Uhal BD. Am J Physiol Lung Cell Mol Physiol 277: L1245-L1250, 1999). This study tested the ability of the angiotensin-converting enzyme inhibitor captopril or the caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone (ZVAD-fmk) to block alveolar epithelial cell apoptosis and lung fibrosis in vivo in response to bleomycin (Bleo). Male Wistar rats received 8 U/kg of Bleo (bleomycin sulfate) or vehicle intratracheally. Subgroups of Bleo-treated rats received captopril, ZVAD-fmk, or vehicle alone. Lung collagen was assessed by picrosirius red or hydroxyproline assay at 1, 7, and 14 days post-Bleo, and apoptosis was detected by in situ end labeling (ISEL). Bleo increased alveolar septal and peribronchial collagen by 100 and 133%, respectively (both P < 0.01), by day 14 but not earlier. In contrast, ISEL was increased in alveolar and airway cells at all time points. Captopril or ZVAD-fmk inhibited collagen accumulation by 91 and 85%, respectively (P < 0. 01). Both agents also inhibited ISEL in alveoli by 99 and 81% and in airways by 67 and 63%, respectively. These data suggest that the efficacy of captopril to inhibit experimental lung fibrogenesis is related to inhibition of apoptosis. They also demonstrate the antifibrotic potential of a caspase inhibitor.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10893213&dopt=Abstract




Am J Physiol Renal Physiol. 2000 Jul;279(1):F122-9.
Nitric oxide regulates renal cortical cyclooxygenase-2 expression.

Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC.

George M. O'Brien Kidney and Urologic Diseases Center and Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennesee 37232, USA.

We have previously shown that cyclooxygenase-2 (COX-2) is localized to the cortical thick ascending limb of the loop of Henle (cTALH)/macula densa of the rat kidney, and expression increases in response to low-salt diet and/or angiotensin-converting enzyme (ACE) inhibition. Because of the localization of neuronal nitric oxide synthase (nNOS) to macula densa and surrounding cTALH, the present study investigated the role of nitric oxide (NO) in the regulation of COX-2 expression. For in vivo studies, rats were fed a normal diet, low-salt diet or low-salt diet combined with the ACE inhibitor captopril. In each group, one-half of them were treated with the nNOS inhibitors 7-nitroinidazole (7-NI) or S-methyl-thiocitrulline. Both of these NOS inhibitors inhibited increases in COX-2 mRNA and immunoreactive protein in response to low salt and low salt+captopril. For in vitro studies, COX-2 expression was studied in primary cultures of rabbit cTALH cells immunodisssected with Tamm-Horsfall antibody. Basal COX-2 immunoreactivity expression was stimulated by S-nitroso-N-acetyl-penicillamine (SNAP), an NO donor, and intracellular cGMP concentration. The cultured cells expressed immunoreactive nNOS, and 7-NI inhibited basal COX-2 immunoreactivity expression, which could be partially overcome by cGMP. In summary, these studies indicate that NO is a mediator of increased renal cortical COX-2 expression seen in volume depletion and suggest important interactions between the NO and COX-2 systems in the regulation of arteriolar tone and the renin-angiotensin system by the macula densa.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10894794&dopt=Abstract













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