Disease relevance of l-Phenylisopropyladenosine

• To avoid raising anti-protein III (PIII)-blocking antibodies and limit potential lipooligosaccharide toxicity, PI was chromatographically isolated with minimal PIII contamination (less than 1%) from Pgh 3-2 (PIB), a serum-sensitive gonococcal strain and UU1 (PIA), a serum-resistant gonococcal strain [1].
• Intravenous PIA 15 minutes before 30-minute ischemia also limited infarct size to 6 +/- 2% at the highest dose [2].
• Hybridization analysis suggests that there is a single structural gene for PI and that it is homologous to the gene found in a PIA-bearing strain of gonococcus [3].
• When rabbits pretreated with PIA were paced at 220 beats per minutes, PIA still limited infarct size (16 +/- 4%), indicating that protection was not the result of bradycardia [2].
• Neonatal alloimmune thrombocytopenia associated with Ca is likely to be as severe as that seen in cases due to incompatibilities for the HPA-1 (PIA) and HPA-4 (Pen) platelet alloantigen systems, because each is located on GPIIIa, a densely represented molecule on the platelet surface [4].

Psychiatry related information on l-Phenylisopropyladenosine

• (B) Compounds 7-11 (8-substituted 1,3-dialkylxanthines) and 19-21 (imidazo[2,1-i]purin-5(4H)-one derivatives) ameliorated the shortened latency in the (R)-PIA-induced amnesia model but not in the scopolamine-induced amnesia model [5].
• The relative potencies of alkylxanthines in reversing locomotor activity depression elicited by L-phenylisopropyladenosine (L-PIA) were similar to relative potencies in competing for adenosine receptors labeled by [3H]cyclohexyladenosine [6].
• Support for construct validity came from moderate correlations with concurrent BASC and PIA scores, analyses of variance showing greater deficits in object relations in pathological subgroups compared with normals, and a trend analysis showed that Alienation scores followed a lawful relationship with increasing severity of psychopathology [7].

High impact information on l-Phenylisopropyladenosine

• The "S" stereoisomer of PIA (S-PIA) was a less potent inhibitor of forskolin stimulated chloride secretion, consistent with the affinity profile of PIA stereoisomers for an A1 receptor [8].
• Propranolol 100 mumol/L, which blocks DAG production from metabolites produced by PLD catalysis, completely abolished the protective effects of both metabolic preconditioning and (R)-PIA exposure in myocytes [9].
• (R)-N6-Phenylisopropyladenosine (PIA) stimulates dopa production 3- to 5-fold in PC12 cells, with a half-maximal effective concentration (EC50) of 50 nM [10].
• Oligonucleotide-based typing of fetuses at risk for NATP whose fathers are heterozygous for the PIA antigens allows early recognition of affected fetuses so that prenatal therapy of mothers can be instituted if necessary [11].
• In contrast, PIA effectively inhibited 3-O-methyl-D-glucose uptake in myocytes even during insulin stimulation [12].

Chemical compound and disease context of l-Phenylisopropyladenosine

• Inhibition of adenylate cyclase by (R)-PIA was attenuated by the A1 receptor antagonist XAC and following inactivation of Gi with pertussis toxin (100 ng/ml) [13].
• After pretreatment with pertussis toxin the inhibitory effects both on force of contraction and on the maximal rate of depolarisation of adenosine and PIA were abolished [14].
• Pertussis toxin treatment abolished the PIA, but not the TSH, action, whereas thapsigargin-induced Ca2+ depletion of the inositol 1,4,5-trisphosphate-sensitive pool inhibited the actions of both TSH and PIA [15].
• Aminophylline, but not enprofylline, reversed the respiratory depression caused by PIA [16].

Biological context of l-Phenylisopropyladenosine

• These data indicate that a PlA1 alloantigenic epitope is located within a small, unglycosylated fragment of GPIIIa containing the polymorphism responsible for the PIA phenotype [17].
• The addition of PIA restored the effect of EGF on both lipolysis and cyclic AMP [18].
• Since EGF decreased the IC50 for the inhibitory effect of PIA on (ISO+ADA)-stimulated lipolysis, we suggest that EGF modulates the interaction between GS and Gi in the control of adenylate cyclase [18].
• From the selective protection of [3H] PIA and [3H]DPCPX binding from inactivation, it is concluded that agonists and antagonists occupy different domains at the binding site [19].
• Unlike normal or hyperplastic epithelium, GSTP1 CpG island hypermethylation can be detected in some PIA lesions [20].

Anatomical context of l-Phenylisopropyladenosine

• We explored the feasibility of allele-specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP [11].
• Molecular modeling identified putative interactions of PIAs with the phosphoinositide-binding site in the PH domain of Akt, and growth factor-induced translocation of Akt to the plasma membrane was inhibited by PIA administration [21].
• These data support the hypothesis that atrophic epithelium in a subset of PIA lesions may lead to high-grade PIN and/or adenocarcinoma [20].
• At least six of the peptides that were found to contain T cell epitopes show homology to constant regions of the meningococcal class 3 OMP and the gonococcal porins PIA and PIB [22].
• Extracellular ATP, N6-(L-2-phenylisopropyl)adenosine (PIA) and other purinergic agonists inhibited atrial natriuretic peptide (ANP)-induced cGMP accumulation in FRTL-5 thyroid cells [23].

Associations of l-Phenylisopropyladenosine with other chemical compounds

• While the nonmetabolizable adenosine analogue N6-(phenylisopropyl)adenosine (PIA) inhibited ADA-stimulated lipolysis, EGF affected neither ADA-stimulated lipolysis nor the dose-response curve for PIA [18].
• In competition experiments, NECA was more potent at inhibiting 125I-PAPA-APEC binding than (R)-PIA, with their respective IC50 values being 5.6 and 351 nM [13].
• Adenosine receptor agonists inhibited the formation of cAMP induced by isoprenaline (IC50 for (R)-PIA, 0.4 nM) [24].
• Insulin-stimulated glucose oxidation was enhanced by the addition of N6 (phenylisopropyl)adenosine (PIA), prostaglandin E1 (PGE1) or nicotinic acid during a 1-h incubation of small amounts 5-8 mg/ml) of rat fat cells [25].
• Furthermore, disruption of the ica operon in a bap-positive strain had no effect on in vitro biofilm formation, a finding which strongly suggested that Bap could compensate for the deficiency of the PIA/PNAG product (a biofilm matrix polysaccharide) [26].

Gene context of l-Phenylisopropyladenosine

• Many of the cells within PIA lesions contain elevated levels of GSTP1, glutathione S-transferase-alpha (GSTA1), and cyclooxygenase-II proteins, suggesting a stress response [20].
• To refine the region toward positional identification, Cia5 subcongenic strains were generated and studied in PIA and CIA [27].
• Both PIA and IL2 receptor-inducing activities were abrogated by treatment of LCM with proteolytic enzymes or by heating at 47 degrees C for 30 min [28].
• The lack of PIA stimulation of basic fibroblast growth factor-induced phospholipase-C gamma activation as well as the rise in [Ca2+]i suggests that the cooperative PIA action occurs specifically on phospholipase-C beta [15].
• Rapid and acute intracellular calcium, however, were observed in HaCaT keratinocytes in response to alpha-MSH (10(-15)-10(-7) M), KPV (10(-15)-10(-7) M), KP-D-V (10(-15)-10(-7) M) and ACTH (10(-15)-10(-7) M), but only in the presence of PIA, an adenosine agonist that inhibits the cyclic AMP pathway [29].

Analytical, diagnostic and therapeutic context of l-Phenylisopropyladenosine

• When the PIA was given at reperfusion, infarct size was 46 +/- 6%, indicating that receptor activation must precede ischemia to protect [2].
• Western blot studies also reveal immunologically conserved domains between the class 1 protein, PIA and PIB [30].
• PIA-genotyping was carried out by standard restriction fragment length analysis (RFLA) of PCR amplified lymphocyte template DNA [31].
• Through immunocytochemistry with the use of antibodies against A1 adenosine receptors (A1Rs) and confocal microscopy, we show that stimulation of A1Rs by the agonist (R)-phenylisopropyladenosine [(R)-PIA] caused a rapid (5-15 min) aggregation (clustering) of receptor molecules on the surface of DDT1MF-2 cells [32].
• Quantification of the content of A1Rs by immunoblotting and flow cytometry in cells pretreated with 50 nM (R)-PIA indicates a time-dependent slow down-regulation of the receptor [32].

References