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Common reference intervals for nationwide use were developed for 40 major tests, based on three multicentre studies by advanced statistical methods. Sex- and age-related profiles of reference values are of great relevance not only for interpreting test results, but for applying clinical decision limits specified in various clinical guidelines.

ADP-ribosyl cyclase activities in cultured rat astrocytes were examined by using TLC for separation of enzymatic products. A relatively high rate of [ 3 H]cyclic ADP-ribose production converted from [3 H]NAD ϩ by ADP-ribosyl cyclase (2.015 Ϯ 0.554 nmol/min/mg of protein) was detected in the crude membrane fraction of astrocytes, which contained ϳ50% of the total cyclase activity in astrocytes. The formation rate of [ 3 H]ADPribose from cyclic ADP-ribose by cyclic ADP-ribose hydrolase and/or from NAD ϩ by NAD glycohydrolase was low and enriched in the cytosolic fraction. Although NAD ϩ in the extracellular medium was metabolized to cyclic ADP-ribose by incubating cultures of intact astrocytes, the presence of Triton X-100 in the medium for permeabilizing cells increased cyclic ADP-ribose production three times as much. Isoproterenol and GTP increased [ 3 H]cyclic ADP-ribose formation in crude membrane-associated cyclase activity. This isoproterenol-induced stimulation of membrane-associated ADP-ribosyl cyclase activity was confirmed by cyclic GDP-ribose formation fluorometrically. This stimulatory action was blocked by prior treatment of cells with cholera toxin but not with pertussis toxin. These results suggest that ADPribosyl cyclase in astrocytes has both extracellular and intracellular actions and that signals of ␤-adrenergic stimulation are transduced to membrane-bound ADP-ribosyl cyclase via G proteins within cell surface membranes of astrocytes. Key Words: ADP-ribosyl cyclase-AstrocyteCyclic ADP-ribose hydrolase -Isoproterenol-NAD ϩ -Membrane-bound ADP-ribosyl cyclase. J. Neurochem. 74, 669 -675 (2000). NADϩ is metabolized to ADP-ribose (ADPR) directly by NAD glycohydrolase or by a two step-enzyme reaction: conversion of NAD ϩ to cyclic ADPR (cADPR) by ADP-ribosyl cyclase and subsequently cADPR to ADPR by cADPR hydrolase. The ADP-ribosyl cyclase is detected in various tissues, from sea urchin eggs to human cardiac myocytes (Rusinko and Lee, 1989; Aarhus, 1991, 1993;Kim et al., 1993;Takasawa et al., 1993;Kukimoto et al., 1996;Lee, 1997). An intermediate of this enzyme reaction, cADPR, is a modulator for mobilizing Ca 2ϩ from ryanodine receptor Ca 2ϩ release channels (Koshiyama et al., 1991;Galione, 1993;Mészáros et al., 1993). In the CNS, it has long been known that an extracellular NAD glycohydrolase-like enzyme in rat brain synaptosomes hydrolyzes NAD ϩ to ADPR (Snell et al., 1984). ADP-ribosyl cyclase is also distributed in neuronal tissues (Rusinko and Lee, 1989). However, the physiological significance of such enzymes (De Flora et al., 1996) is not well understood in relation to the synaptic transmission in the extracellular synaptic cleft and intracellular signal transduction (Snell et al., 1984).Recently, a predominantly extracellular localization of ADP-ribosyl cyclase activity has been shown in cultured cortical astrocytes (Pawlikowska et al., 1996). However, in light of what is now known on the intracellular function of cADPR (Galione et al., 1991;Lee, 1994;Sitsapesan et al., 1995;Guo a...

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