Xanthine

About: Xanthine is a research topic. Over the lifetime, 4046 publications have been published within this topic receiving 129820 citations. The topic is also known as: Xanthine.

Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines.

Abstract: 1. The potencies of caffeine and related methylxanthines as adenosine antagonists were assessed with respect to three apparent subtypes of adenosine receptors in rat brain preparations: (i) the A1-adenosine receptor which binds with a very high affinity the ligand [3H]cyclohexyladenosine (KD, 1 nM) in rat brain membranes; (ii) a ubiquitous low-affinity A2-adenosine receptor which activates cyclic AMP accumulation in rat brain slices—this A2-adenosine system exhibits an EC50 for 2-chloroadenosine of about 20µM; and (iii) a relatively high-affinity A2-adenosine receptor which activates adenylate cyclase in rat striatal membranes—this A2-adenosine system exhibits an EC50 for 2-chloroadenosine of about 0.5µM and is present in striatal but not in cerebral cortical membranes. 2. The rank order of potency for methylxanthines versus binding of 1 nM [3H]cyclohexyladenosine in membranes from eight rat brain regions is theophylline (IC50, 20–30µM) > paraxanthine (IC50, 40–65µM) > caffeine (IC50, 90–110µM) > theobromine (IC50, 210–280µM). There thus appears to be little difference in A1-receptors in different brain regions in terms of interaction with these methylxanthines. 1-Methylxanthine is more potent than caffeine in rat cerebral cortical membranes, while 3-methylxanthine and 7-methylxanthine are less potent than caffeine. 3. The rank order of potency for methylxanthines versus activation of cyclic AMP accumulation by 50µM 2-chloroadenosine in rat striatal slices is theophylline (IC50, 60µM) > paraxanthine (IC50, 90µM) > caffeine (IC50, 120µM) » theobromine (IC50, > 1000µM). Similar potencies pertain in cerebral cortical slices. 4. The rank order of potency of methylxanthines versus activation of adenylate cyclase by 1µM 2-chloroadenosine in rat striatal membranes is theophylline (IC50, 20µM) > paraxanthine (IC50, 40µM) > caffeine (IC50, 80µM) » theobromine (IC50, > 1000µM). 5. Caffeine and other methylxanthines, thus, antagonize effectively both A1- and A2-adenosine receptors in brain perparations. Theobromine appears less effective versus A2-receptors than versus A1-receptors. Caffeine exhibits aKi value of about 50µM at the very high-affinity A1-binding sites, aKi value of about 30µM at the low-affinity A2-adenosine site in brain slices, and aKi value of about 27µM at the high-affinity A2-adenosine site in striatal membranes. The functional significance of antagonism of such adenosine receptors by caffeinein situ will depend both on the local levels of adenosine and on the affinity for adenosine for the receptor, since antagonism by xanthines is competitive in nature. In addition, the functional significance of xanthine action will depend on the degree of inhibition of adenosine input which is required to alter the output signal. For a stimulatory input to adenylate cyclase via an A2-adenosine receptor, profound antagonism by methylxanthines is probably required to alter the cyclic AMP-mediated output signal, while for inhibitory input to adenylate cyclase via an A1-adenosine receptor, presumably a lesser degree of antagonism by methylxanthines may be required to alter the cyclic AMP-mediated output signal.

Flavoprotein structure and mechanism. 4. Xanthine oxidase and xanthine dehydrogenase.

Abstract: Xanthine oxidase and xanthine dehydrogenase are enzymes involved in the metabolism of purines and pyrimidines in various organisms. Their relationship to one another has been the subject of considerable debate, primarily because of their proposed roles in ischemia/reperfusion damage in tissues. Differences in the kinetics and oxidation-reduction behavior of the two forms are accounted for by the presence in the dehydrogenase of a binding site for NAD+, as well as a substantially lower reduction potential for the flavin FADH./FADH2 couple of the dehydrogenase relative to the oxidase. This review presents recent advances of our understanding of the biochemistry and molecular biology of these systems, including a model for the overall morphology of xanthine oxidizing enzymes. The evidence that the two enzymes represent alternate forms of the same gene product, in some cases reversibly interconvertible between one another, is discussed.