Disease relevance of Isopropylphenyladenosine

• In an attempt to elucidate the mechanism of inhibition, we have examined the effect of pertussis toxin (PTX) on the ability of the stable adenosine analogue (-)phenylisopropyladenosine (PIA) to inhibit glutamate release from cerebellar neurones maintained in primary culture [1].
• 3. Hypothyroidism also enhanced inhibition of adenylate cyclase by phenylisopropyladenosine (with 100 mM-Na+ and 10 microM-GTP present) [2].
• In the absence of DPCPX both the functional depression and arrhythmias induced by ISO were prevented in the presence of phenylisopropyladenosine (PIA; 1 microM; A1 receptor agonist) [3].
• Quinolinic acid neurotoxicity: protection by intracerebral phenylisopropyladenosine (PIA) and potentiation by hypotension [4].

High impact information on Isopropylphenyladenosine

• Phenylisopropyladenosine (an adenosine deaminase-resistant adenosine analog) prevented or reversed both adenosine deaminase-stimulated phosphorylation and activation of CGI-PDE (IC50 approximately 0.2 nM) [5].
• The ability of phenylisopropyladenosine (PIA) to modulate basal and maximal insulin-stimulated glucose uptake was compared in adipocytes from SHR and WKY rats [6].
• The effect of adenosine removal was reversed by addition of phenylisopropyladenosine (500 nM), which is resistant to hydrolysis by the deaminase [7].
• The inhibitory actions of PIA on adenylate cyclase were blocked by the adenosine receptor antagonists, theophylline and isobutylmethylxanthine [8].
• However, subsequent addition of phenylisopropyladenosine nearly restored transport activity without alteration of A-kinase activity [9].

Chemical compound and disease context of Isopropylphenyladenosine

• Cells were preincubated for 18-24 h with pertussis toxin, and the responses to FSH and to the adenosine analog phenylisopropyladenosine (PIA) were measured by assaying cAMP accumulation [10].
• Hypothyroidism resulted in decreased sensitivity to noradrenaline and increased sensitivity to phenylisopropyladenosine [11].
• We recently discovered that in FRTL-5 cells the P1-purinergic agonist PIA (phenylisopropyladenosine) markedly enhanced P2-purinergic agonist-induced responses in an IAP (islet-activating protein or pertussis toxin)-sensitive manner [12].
• The effect of mastoparan was not additive to that of phenylisopropyladenosine and was completely abolished by pretreatment of adipocytes with pertussis toxin (1 microg/ml for 2 hours) [13].

Biological context of Isopropylphenyladenosine

• Adenosine and alpha(2)-adrenergic antilipolytic effects were estimated through the inhibition of theophylline-induced lipolysis by phenylisopropyladenosine and clonidine, respectively [14].
• In 125I-cyanopindolol/isoproterenol competitive binding experiments phenylisopropyladenosine (PIA) significantly increased the IC50 for isoproterenol from 48 +/- 6 nM to 140 +/- 48 nM and steepened the slope of the competition curves from -0.56 +/- 0.03 to -0.90 +/- 0.21 [15].

Anatomical context of Isopropylphenyladenosine

• 5. The effect of GTP in modifying the displacement of the antagonist [3H]diethylphenylxanthine from synaptosomal membranes by unlabelled phenylisopropyladenosine was more pronounced in the hypothyroid state [2].
• (4) Diabetes decreased the GTP-dependent right-wards shift in the dose-curve for displacement of the antagonist [3H]DPCPX by PIA in adipocyte plasma membranes [16].
• Conversely, the response to the antilipolytic effector, phenylisopropyladenosine (PIA), was significantly reduced in adipose tissue explants from ST or fasted cows [17].

Associations of Isopropylphenyladenosine with other chemical compounds

• In the presence of GTP, adenylyl cyclase activity in S49, NS-20, and CL was stimulated respectively by isoproterenol and prostaglandin E1 (PGE1), by PGE1 and the adenosine analog, phenylisopropyladenosine, and by PGE1 and isoproterenol, with the first of the listed stimulants eliciting higher activities than the second [18].
• Lowering of serum GH levels, by treatment of rats with an antiserum (anti-rGH) specific for rat GH, increased the sensitivity of adipocytes to the anti-lipolytic agonists N6-phenylisopropyladenosine (PIA) and prostaglandin E1 [19].
• The adenosine A1-receptor agonist N6-(phenylisopropyl)-adenosine (PIA) had a powerful negative inotropic effect in ISO-stimulated atria [20].
• Adipocytes were incubated with adenosine deaminase followed by epinephrine, isoproterenol, or epinephrine plus phenylisopropyladenosine, and glycerol release was measured [21].
• (1) Streptozotocin-diabetes decreased the responsiveness of noradrenaline- or forskolin-stimulated lipolysis to inhibition by phenylisopropyladenosine (PIA), prostaglandin E1 (PGE1) and nicotinate in rat adipocytes [16].

Gene context of Isopropylphenyladenosine

• Second, EEDQ did not alter the inhibition of forskolin-stimulated adenylyl cyclase activity induced by the adenosine A1 receptor agonist phenylisopropyladenosine (PIA).(ABSTRACT TRUNCATED AT 400 WORDS)[22]
• Although NaCl-free HBSS improved TSH- or Graves' IgG-induced IP and cAMP production in cells with recombinant TSHR; the modulatory action of phenylisopropyladenosine was lost [23].
• The increase in 3H-thymidine incorporation induced by hexosaminidase B was also inhibited by mannan and PIA [24].
• By using phenylisopropyladenosine to block IFN-induced lipolysis, we found that in the absence of increased FA flux, INF gamma did not exert a ketogenic effect [25].
• The ability of GH to modulate the PIA-activated adenosine receptor to stimulate dissociation of heterotrimeric Gi was assessed by measurement of pertussis toxin-catalysed ADP-ribosylation of Gi; GH does not appear to alter the interaction between the activated receptor and Gi [26].

Analytical, diagnostic and therapeutic context of Isopropylphenyladenosine

• To determine its mechanisms at the level of receptor-G-protein activation, the present studies examined the effect of T62 on A1-stimulated [35S]guanosine-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding in brain membranes, and by [35S]GTPgammaS autoradiography using the A1 agonist, phenylisopropyladenosine (PIA), to activate G-proteins [27].

References