Online Pharmacy, Tramadol, Paxil, antibiotics, amoxicillin, zithromax, Rx Online, pharmaceuticals, DHEA, prescription medications, prescription drugs.

Drugs online research references

J Cardiovasc Pharmacol. 2000 Nov;36(5):656-68.
Cardiac ischemia oxidizes regulatory thiols on ryanodine receptors: captopril acts as a reducing agent to improve Ca2+ uptake by ischemic sarcoplasmic reticulum.

Menshikova EV, Salama G.

Department of Cell Biology and Physiology, University of Pittsburgh, School of Medicine, Pennsylvania 15261, USA.

We tested the hypothesis that ischemia alters sarcoplasmic reticulum (SR) Ca2+ transport by oxidizing regulatory thiols on ryanodine receptors (RyRs), and that membrane-permeable sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitors protect against ischemia-induced oxidation and explain in part, the therapeutic actions of captopril. Ca2+ uptake and adenosine triphosphatase (ATPase) activity was measured from SR vesicles isolated from control or ischemic dog and human ventricles and compared with or without sulfhydryl reductants. The rate and amount of Ca2+ uptake was lower for canine ischemic SR compared with control (6.5 +/- 0.2 --> 18.5 +/- 1.1 nmol Ca2+/mg/min and 123.1 +/- 4.7 --> 235.0 +/- 17.3 nmol Ca2+/mg; n = 8 each). Captopril, dithiothreitol (DTT), glutathione (GSH), and L-cysteine increased the rate and amount of Ca2+ uptake by canine and human ischemic SR vesicles by approximately 50%. Reducing agents had no effect on Ca2+- ATPase activity in either canine control or ischemic (approximately 40% less than control) SR. Captopril was as potent as DTT at reversing the oxidation of skeletal and cardiac RyRs induced by reactive disulfides (RDSs) or nitric oxide (NO). In neonatal rat myocytes, RDSs or NO triggered SR Ca2+ release and increased cytosolic Ca2+, an effect reversed by captopril and DTT but not GSH or cysteine. Pretreatment of myocytes with captopril (exposure and then wash) inhibited Ca2+ elevation elicited by RDSs or NO, indicating that captopril is an effective, membrane-permeable intracellular reducing agent. Thus, net SR Ca2+ accumulation is reduced by ischemia in part due to the oxidation of thiols that gate RyRs, an effect reversed by captopril.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11065227&dopt=Abstract

J Biol Chem. 2001 Feb 16;276(7):4998-5004. Epub 2000 Nov 06.
Angiotensin I-converting enzyme transition state stabilization by HIS1089: evidence for a catalytic mechanism distinct from other gluzincin metalloproteinases.

Fernandez M, Liu X, Wouters MA, Heyberger S, Husain A.

Enzyme Research Unit, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.

Angiotensin (Ang) I-converting enzyme (ACE) is a member of the gluzincin family of zinc metalloproteinases that contains two homologous catalytic domains. Both the N- and C-terminal domains are peptidyl-dipeptidases that catalyze Ang II formation and bradykinin degradation. Multiple sequence alignment was used to predict His(1089) as the catalytic residue in human ACE C-domain that, by analogy with the prototypical gluzincin, thermolysin, stabilizes the scissile carbonyl bond through a hydrogen bond during transition state binding. Site-directed mutagenesis was used to change His(1089) to Ala or Leu. At pH 7.5, with Ang I as substrate, k(cat)/K(m) values for these Ala and Leu mutants were 430 and 4,000-fold lower, respectively, compared with wild-type enzyme and were mainly due to a decrease in catalytic rate (k(cat)) with minor effects on ground state substrate binding (K(m)). A 120,000-fold decrease in the binding of lisinopril, a proposed transition state mimic, was also observed with the His(1089) --> Ala mutation. ACE C-domain-dependent cleavage of AcAFAA showed a pH optimum of 8.2. H1089A has a pH optimum of 5.5 with no pH dependence of its catalytic activity in the range 6.5-10.5, indicating that the His(1089) side chain allows ACE to function as an alkaline peptidyl-dipeptidase. Since transition state mutants of other gluzincins show pH optima shifts toward the alkaline, this effect of His(1089) on the ACE pH optimum and its ability to influence transition state binding of the sulfhydryl inhibitor captopril indicate that the catalytic mechanism of ACE is distinct from that of other gluzincins.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11067854&dopt=Abstract

Comp Biochem Physiol Comp Physiol. 1992 Apr;101(4):819-25.
The vasopressor action of angiotensin in the snake Bothrops jararaca.

Breno MC, Picarelli ZP.

Servico de Farmacologia, Instituto Butantan, Sao Paulo, Brazil.

1. Carotid blood pressure from anesthetized B. jararaca snakes was recorded in order to study angiotensin action in this reptile. 2. Whereas [Asn1,Val5] AII and AIII were less potent than [Asp1,Ile5] AII and [Asp1,Val5] AII, [Sar1,Ile5] AII was slightly more potent. 3. Captopril abolished the responses to AI (0.01-3 micrograms/kg). 4. [Sar1,Ala8] AII was uneffective but [Sar1,Leu8] AII or phenoxybenzamine were able to reduce AII vasopressor responses. 5. These results led to the conclusion that the vasopressor response of AII in B. jararaca is due to an interaction with its own receptor but, part of the AII receptor population seems to be coupled to the sympatho-adrenal system. Moreover, structural requirements seem to be necessary for the AII response in B. jararaca.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1351456&dopt=Abstract

online pharmacies || Hair Million herbal formula for hair loss and hair growth || Amoxicillin || Tramadol || Paxil || Rx Drugs USA, Prescription Drugs Online Pharmacy || Zithromax || online pharmacy || Antibiotics and prescription medications online literature || Antibiotics