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Chemical Compound Review

l-Phenylisopropyladenosine     (2R,3S,4R,5R)-2- (hydroxymethyl)-5-[6...

Synonyms: L-PIA, CHEMBL139000, AG-K-04012, SureCN8907369, R-(-)-PIA, ...
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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


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


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].


  1. Characterization and specificity of antibodies to protein I of Neisseria gonorrhoeae produced by injection with various protein I-adjuvant preparations. Wetzler, L.M., Blake, M.S., Gotschlich, E.C. J. Exp. Med. (1988) [Pubmed]
  2. Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction. Thornton, J.D., Liu, G.S., Olsson, R.A., Downey, J.M. Circulation (1992) [Pubmed]
  3. Porin protein of Neisseria gonorrhoeae: cloning and gene structure. Gotschlich, E.C., Seiff, M.E., Blake, M.S., Koomey, M. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  4. Neonatal alloimmune thrombocytopenia due to a new platelet-specific alloantibody. McFarland, J.G., Blanchette, V., Collins, J., Newman, P.J., Wang, R., Aster, R.H. Blood (1993) [Pubmed]
  5. Adenosine A1 antagonists. 3. Structure-activity relationships on amelioration against scopolamine- or N6-((R)-phenylisopropyl)adenosine-induced cognitive disturbance. Suzuki, F., Shimada, J., Shiozaki, S., Ichikawa, S., Ishii, A., Nakamura, J., Nonaka, H., Kobayashi, H., Fuse, E. J. Med. Chem. (1993) [Pubmed]
  6. Interactions in the behavioral effects of methylxanthines and adenosine derivatives. Katims, J.J., Annau, Z., Snyder, S.H. J. Pharmacol. Exp. Ther. (1983) [Pubmed]
  7. Bell object relations inventory for adolescents and children: reliability, validity, and factorial invariance. Bell, M. Journal of personality assessment. (2003) [Pubmed]
  8. A1 adenosine receptors inhibit chloride transport in the shark rectal gland. Dissociation of inhibition and cyclic AMP. Kelley, G.G., Poeschla, E.M., Barron, H.V., Forrest, J.N. J. Clin. Invest. (1990) [Pubmed]
  9. Phospholipase D plays a role in ischemic preconditioning in rabbit heart. Cohen, M.V., Liu, Y., Liu, G.S., Wang, P., Weinbrenner, C., Cordis, G.A., Das, D.K., Downey, J.M. Circulation (1996) [Pubmed]
  10. Adenosine-dependent activation of tyrosine hydroxylase is defective in adenosine kinase-deficient PC12 cells. Erny, R., Wagner, J.A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  11. Prenatal diagnosis of neonatal alloimmune thrombocytopenia using allele-specific oligonucleotide probes. McFarland, J.G., Aster, R.H., Bussel, J.B., Gianopoulos, J.G., Derbes, R.S., Newman, P.J. Blood (1991) [Pubmed]
  12. Myocardial glucose utilization. Failure of adenosine to alter it and inhibition by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine. Dale, W.E., Hale, C.C., Kim, H.D., Rovetto, M.J. Circ. Res. (1991) [Pubmed]
  13. Demonstration of both A1 and A2 adenosine receptors in DDT1 MF-2 smooth muscle cells. Ramkumar, V., Barrington, W.W., Jacobson, K.A., Stiles, G.L. Mol. Pharmacol. (1990) [Pubmed]
  14. Inhibition of the effects of adenosine on force of contraction and the slow calcium inward current by pertussis toxin is associated with myocardial lesions. Böhm, M., Brückner, R., Schäfer, H., Schmitz, W., Scholz, H. Cardiovasc. Res. (1988) [Pubmed]
  15. Cooperation of thyrotropin, but not basic fibroblast growth factor, with an adenosine receptor agonist in Ca2+ mobilization from thapsigargin-sensitive pools in single FRTL-5 thyroid cells. Sho, K., Okajima, F., Kondo, Y. Endocrinology (1995) [Pubmed]
  16. Effects of adenosine and xanthine derivatives on breathing during acute hypoxia in the anesthetized newborn piglet. Darnall, R.A., Bruce, R.D. Pediatr. Pulmonol. (1987) [Pubmed]
  17. Localization of a PlA1 epitope to the amino terminal 66 residues of platelet glycoprotein IIIa. Bowditch, R.D., Tani, P.H., Halloran, C.E., Frelinger, A.L., McMillan, R., Ginsberg, M.H. Blood (1992) [Pubmed]
  18. Epidermal growth factor modulates the lipolytic action of catecholamines in rat adipocytes. Involvement of a Gi protein. Tebar, F., Ramírez, I., Soley, M. J. Biol. Chem. (1993) [Pubmed]
  19. Chemical modification of A1 adenosine receptors in rat brain membranes. Evidence for histidine in different domains of the ligand binding site. Klotz, K.N., Lohse, M.J., Schwabe, U. J. Biol. Chem. (1988) [Pubmed]
  20. Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. Nakayama, M., Bennett, C.J., Hicks, J.L., Epstein, J.I., Platz, E.A., Nelson, W.G., De Marzo, A.M. Am. J. Pathol. (2003) [Pubmed]
  21. Preferential inhibition of Akt and killing of Akt-dependent cancer cells by rationally designed phosphatidylinositol ether lipid analogues. Castillo, S.S., Brognard, J., Petukhov, P.A., Zhang, C., Tsurutani, J., Granville, C.A., Li, M., Jung, M., West, K.A., Gills, J.G., Kozikowski, A.P., Dennis, P.A. Cancer Res. (2004) [Pubmed]
  22. T cell recognition of Neisseria meningitidis class 1 outer membrane proteins. Identification of T cell epitopes with selected synthetic peptides and determination of HLA restriction elements. Wiertz, E.J., van Gaans-van den Brink, J.A., Schreuder, G.M., Termijtelen, A.A., Hoogerhout, P., Poolman, J.T. J. Immunol. (1991) [Pubmed]
  23. Inhibition of atrial natriuretic peptide-induced cGMP accumulation by purinergic agonists in FRTL-5 thyroid cells. Involvement of both pertussis toxin-sensitive and insensitive mechanisms. Okajima, F., Kondo, Y. J. Biol. Chem. (1990) [Pubmed]
  24. Characterization of adenosine A1 receptors in intact DDT1 MF-2 smooth muscle cells. Gerwins, P., Nordstedt, C., Fredholm, B.B. Mol. Pharmacol. (1990) [Pubmed]
  25. Insulin, prostaglandin E1, PHENYLISOPROPYLADENOSINE AND NICOTINIC ACID AS REGULATORS OF FAT CELL METABOLISM. Wieser, P.B., Fain, J.N. Endocrinology (1975) [Pubmed]
  26. Role of biofilm-associated protein bap in the pathogenesis of bovine Staphylococcus aureus. Cucarella, C., Tormo, M.A., Ubeda, C., Trotonda, M.P., Monzón, M., Peris, C., Amorena, B., Lasa, I., Penadés, J.R. Infect. Immun. (2004) [Pubmed]
  27. The non-MHC quantitative trait locus Cia5 contains three major arthritis genes that differentially regulate disease severity, pannus formation, and joint damage in collagen- and pristane-induced arthritis. Brenner, M., Meng, H.C., Yarlett, N.C., Joe, B., Griffiths, M.M., Remmers, E.F., Wilder, R.L., Gulko, P.S. J. Immunol. (2005) [Pubmed]
  28. Media conditioned by human leukemic T-cells induce expression of IL2 receptors and proliferation of normal T lymphocytes. Kosmatopoulos, C., Allouche, M., Triebel, F., Zanti, M., Clemenceau, C., Gluckman, J.C., Jasmin, C., Georgoulias, V. Int. J. Cancer (1986) [Pubmed]
  29. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells. Elliott, R.J., Szabo, M., Wagner, M.J., Kemp, E.H., MacNeil, S., Haycock, J.W. J. Invest. Dermatol. (2004) [Pubmed]
  30. The class 1 outer membrane protein of Neisseria meningitidis: gene sequence and structural and immunological similarities to gonococcal porins. Barlow, A.K., Heckels, J.E., Clarke, I.N. Mol. Microbiol. (1989) [Pubmed]
  31. Genetic variation of the platelet- surface integrin GPIIb-IIIa (PIA1/A2-SNP) shows a high association with Type 2 diabetes mellitus. Tschoepe, D., Menart, B., Ferber, P., Altmann, C., Haude, M., Haastert, B., Roesen, P. Diabetologia (2003) [Pubmed]
  32. Ligand-induced phosphorylation, clustering, and desensitization of A1 adenosine receptors. Ciruela, F., Saura, C., Canela, E.I., Mallol, J., Lluís, C., Franco, R. Mol. Pharmacol. (1997) [Pubmed]
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