Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pipecolic Acids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed2002

Effects of A(3) adenosine receptor activation and gene knock-out in ischemic-reperfused mouse heart.

OBJECTIVES: To characterize effects of A(3) adenosine receptor (A(3)AR) activation and gene knock-out on responses to ischemia-reperfusion in mouse heart. METHODS: Perfused hearts from wild-type and A(3)AR gene knock-out (A(3)AR KO) mice were subjected to 20 min ischemia and 30 min reperfusion. Functional responses were assessed and changes in energy metabolism and cytosolic pH monitored via 31P-NMR spectroscopy. RESULTS: Selective A(3)AR agonism with 100 nM 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (chloro-IB-MECA) enhanced post-ischemic contractile recovery without altering contracture development in wild-type hearts, an effect unrelated to non-selective activation of A(1) or A(2) adenosine receptors. Chloro-IB-MECA also improved recovery in hearts overexpressing A(1)ARs. Paradoxically, post-ischemic recovery was enhanced by A(3)AR KO. Developed pressure, +dP/dt, and -dP/dt all recovered to higher levels in A(3)AR KO (70-80% of pre-ischemia) vs. wild-type hearts (45-50% of pre-ischemia) (P<0.05). Enhanced recovery was unrelated to recoveries of ATP, phosphocreatine (PCr), inorganic phosphate (P(i)), energy state ([ATP]/[ADP] x [P(i)], DeltaG(ATP)) or cytosolic pH. CONCLUSIONS: Selective A(3)AR activation is cardioprotective in wild-type hearts and hearts overexpressing A(1)ARs, yet A(3)AR gene deletion generates an ischemia-tolerant phenotype without altering energy metabolism or pH. This may be due to compensatory changes or undefined genotypic differences in A(3)AR KO vs. wild-type hearts.

Adenosine↗
PubMed2002

Substitution of Gly-548 to Ala in the substrate binding pocket of prothrombin Perijá leads to the loss of thrombin proteolytic activity.

Prothrombin Perijá is a dysprothrombin derived from a homozygous patient that manifests low thrombin activity upon activation in a one-stage assay. Purified prothrombin Perijá showed normal appearance on SDS-PAGE. and was cleaved normally to form alpha-thrombin by the prothrombinase complex. The activated form, thrombin Perijá, however, did not show any proteolytic activity towards native substrates, fibrinogen, protein C or various synthetic substrates for alpha-thrombin, but it was able to bind to antithrombin III, although the binding capacity was markedly reduced even in the presence of heparin. Thrombin Perijá showed full reactivity toward a small inhibitor, DFP, indicating that the molecular defect is in the substrate binding site in the thrombin molecule but not in the active site itself. By DNA sequence analysis of the patient prothrombin gene, we identified a G to C mutation at nucleotide 20016 in exon 14, which predicts a Gly-548 to Ala substitution in the prothrombin Perijá molecule. The structural modeling of thrombin Perijá suggests that Ala-548 is located close to the limb of the cavity wall of the substrate binding pocket, and that the methyl group blocks protrusion of the guanidino group of Arg into the cavity. This steric hindrance may well inhibit the access of Arg-containing substrates to the catalytic Ser-525 leading to the loss of proteolytic activity.

Alanine↗
PubMed1999

Pharmacological effects of a novel recombinant hirudin, CX-397, in vivo and in vitro: comparison with recombinant hirudin variant-1, heparin, and argatroban.

The novel recombinant hirudin analog CX-397 was investigated with respect to its pharmacological activity and antithrombin profiles in vivo and in vitro. In three different types of thrombosis models in rats, including stasis and thrombin-induced venous, glass surface-activated arterio-venous shunt, and ferric chloride-induced arterial thrombosis models, CX-397 and rHV-1 elicited potent antithrombotic effects, where the minimum effective doses of rHV-1 tended to be higher than those of CX-397 in the arterio-venous shunt and arterial thrombosis models. The hemorrhagic risk of CX-397 in template bleeding in rats was not higher than that of rHV-1, indicating that CX-397 is superior to rHV-1 for treating the platelet-dominant type of thrombosis. However, no differences were detected between CX-397 and rHV-1 in their effects on in vitro coagulation times and thrombin-induced platelet aggregation, suggesting the possibility that some unknown mechanisms other than simple thrombin inhibition are also involved in their antithrombotic actions.

Amino Acid Sequence↗
PubMed1984

Effect of excitatory amino acid antagonists on the high pressure neurological syndrome in rats.

The onset pressures for the tremor, myoclonus and convulsions seen in the high pressure neurological syndrome (HPNS) are increased following cis-2,3-piperidine dicarboxylic acid 1 mmol/kg in the rat. Glutamic acid diethyl ester 1-3 mmol/kg has no effect on tremor or myoclonus, but increases the convulsion pressure when 3 mmol/kg is given immediately before compression. These and earlier data with 2-amino-7-phosphonoheptanoic acid suggest that excitation at the N-methyl-D-aspartate receptor is important in HPNS tremor, and that excitation at the quisqualate receptor contributes to HPNS convulsions.

Animals↗
PubMed1993

Involvement of the "tethered ligand" receptor in thrombin-induced endothelium-mediated relaxations.

The mechanisms by which the serine protease, alpha-thrombin, mediates relaxations were examined in isolated dog and pig coronary arteries and dog saphenous veins. In rings of coronary arteries and saphenous veins contracted submaximally with prostaglandin F2 alpha or U46619, alpha-thrombin (0.1-10 nM) caused relaxations that were abolished by treatment with N omega-nitro-L-arginine (L-NNA) or removal of the endothelium, indicating that the relaxations were mediated by endothelium-derived nitric oxide. These relaxations were blocked by the thrombin active site inhibitor, MD-805, indicating the requirement of thrombin's catalytic site to induce the relaxations. The thrombin exosite inhibitor, BMS-180742, decreased the sensitivity to alpha-thrombin without altering maximal relaxations. Indomethacin, a cyclooxygenase inhibitor, had no inhibitory effect on the relaxations caused by alpha-thrombin, indicating that the relaxations were not mediated by cyclooxygenase products. Similar to alpha-thrombin, the thrombin receptor activating peptide (human sequence: SFLLRNP, 1-100 microM) caused relaxations in pig coronary artery and dog saphenous vein but not in dog coronary artery. These relaxations were blocked by L-NNA but not by indomethacin. The results indicate that alpha-thrombin induces endothelium-dependent relaxations by a novel signaling mechanism that involves proteolytic cleavage of the thrombin receptor to expose a new amino terminus that functions as a "tethered peptide ligand" to activate thrombin receptors on the endothelial cells and release nitric oxide.

Amino Acid Sequence↗
PubMed1994

The role of P-type calcium channels in the depolarization-induced activation of nitric oxide synthase in frontal cortex.

In this study we demonstrate that 50 mM K+ stimulates the conversion of L-[3H]arginine to L-[3H]citrulline and that this effect is blocked by 10 microM N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, and Ca(2+)-free conditions. Amiloride (1 mM) and low Na+ conditions were used to test the possible involvement of the Na(+)-Ca2+ exchanger. These treatments were without effect. The calcium channel blockers 10 mM Mg2+, 100 microM Cd2+, and 10 mM Co2+ also blocked the K+ response, suggesting the involvement of voltage-dependent calcium channels (VDCCs). The specific VDCC involved seems to be the P type, as funnel-web spider toxin blocked the response whereas 200 microM Ni2+, 10 microM nifedipine, and 100 nM omega-conotoxin did not.

Amiloride↗
PubMed1989

Behavioural and electroencephalographic effects of excitatory amino acid antagonists and sigma opiate/phencyclidine-like compounds in rats.

The present work was a comparative study of the electrocortical and behavioural effects of phencyclidine-like drugs and sigma-opiate drugs and of some excitatory amino acid antagonists. Phencyclidine-like drugs and sigma-opiate drugs elicited three dose-dependent electrocortical patterns: 1. Increase of periods of cortical desynchronization 2. Increase of the amplitude of fast (20-30 Hz) cortical waves; 3. Appearance of typical cortical complexes consisting of slow-wave (0.5-2 Hz) sharp-wave complexes. These effects were accompanied by excitatory motor symptoms, such as stereotyped movements of the neck and limbs. The NMDA competitive antagonist D,L-2-amino-5-phosphonovaleric acid (D,L-AP5), administered intracerebroventricularly (0.25-2 mumol), elicited phencyclidine-like stereotyped behaviour and cortical desynchronization, but failed to elicit/sigma typical cortical complexes. The non-selective amino acid antagonist cis-2,3 piperidine dicarboxilic acid (cis 2,3-PDA), administered intraperitoneally (3.3 mmol) failed to elicit both stereotyped behaviour and typical phencyclidine/sigma cortical complexes. The results strongly suggest the hypothesis that a reduction of excitatory amino acid neurotransmission, utilizing N-methyl-d-aspartate (NMDA)-preferring receptors, may be involved in the genesis of phencyclidine/sigma-induced stereotyped behaviour.

2-Amino-5-phosphonovalerate↗