Plasma and urine cyclic nucleotide levels in patients with neoplastic diseases

Peracchi, M.; Lombardi, Luigia; Toschi, Vincenzo; Bamonti-Catena, F.; Mandelli, V.; Maiolo, Anna Teresa; Baldini, Luca; Polli, E.

doi:10.1002/1097-0142(19841215)54:12<3028::aid-cncr2820541235>3.0.co;2-#

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…The plasma, urine and intracellular cAMP levels were shown to be decreased in various malignancies, in particular in chronic lymphocytic leukaemia (CLL) [11][12][13][14]. In CLL lymphocytes, both the density of b 2 -AR on the cell surface and the response to catecholamines are diminished [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Defects of β₂‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression

Kamp

Liebl²,

Haen³

et al. 1997

Eur J Clin Investigation

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The second messenger 3':5'-cyclic adenosine monophosphate (cAMP) inhibits the proliferation of human B lymphocytes. In lymphoid malignancies, cAMP levels or the number of beta 2-adrenergic receptors seem to be decreased. In order to explore this phenomenon further, the function of the beta 2-adrenergic receptor complex was examined in mononuclear leucocytes (MNLs) from patients with B-cell chronic lymphocytic leukaemia (CLL). Peripheral blood MNLs from 25 CLL patients (16 male, nine female: aged 62 +/- 9 years) and 10 healthy volunteers (seven male, three female; aged 47 +/- 19 years) were used. The binding characteristics of beta 2-adrenergic receptors (beta 2-AR) on MNLs were determined by radioligand binding assays with [125I]-cyanopindolol ([125I]-CYP). The number of high-affinity binding sites for [125I]-CYP was significantly lower in CLL patients (313 +/- 300 sites per cell; mean +/- SD) than in control subjects (1479 +/- 1268 sites per cell). Moreover, the density of beta 2-AR decreased with disease progression, from Binet stage A (371 +/- 236, n = 13) to B (236 +/- 136, n = 7) and C (141 +/- 59, n = 5) (P < 0.05; Kruskal-Wallis analysis). Functional analyses of the beta 2-AR complex were performed by measuring the cellular cAMP content of MNLs in response to different stimulators. The cAMP production of MNLs upon isoprenaline stimulation (ISO; 10 min, 10(-4) mol L-1) was slightly lower in CLL patients (12.5 +/- 7.04 pmol 10(-6) cells) than in control subjects (15.91 +/- 10.08 pmol 10(-6) cells), and decreased with CLL progression (stage A 14 +/- 7; stage B 13.66 +/- 3.91; stage C 3.07 +/- 0.79 pmol 10(-6) cells). In contrast, cAMP accumulation in response to cholera toxin (CHO; 10(-4) gml-1, 120 min) was not different in control subjects (70.07 +/- 31.30 pmol 10(-6) cells) and CLL patients (stage A 95.24 +/- 123.07, stage B 70.76 +/- 57.37, stage C 33.21 +/- 33.73 pmol 10(-6) cells). When stimulated with forskolin (100 mumol L-1, 15 min), control MNLs produced about ten-fold more cAMP than CLL MNLs (188.56 +/- 92.53 vs. 17.88 +/- 10.32 pmol 10(-6) cells); this response was not stage dependent. Taken together, the results show that the beta 2-AR transmembrane signalling is impaired in CLL patients. The correlation of some beta 2-AR signalling defects with disease progression suggests that they may contribute to the disease progression of CLL patients.

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Section: Introductionmentioning

confidence: 99%

Defects of β₂‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression

Kamp

Liebl²,

Haen³

et al. 1997

Eur J Clin Investigation

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“…Kinetic parameters ( K m and V max ) have not been reported for hRBC guanyl cyclase and adenyl cyclase, or cnPDEs (cyclic nucleotide phosphodiesterases). Extracellular (plasma) concentrations of 13.6 nM and 4.1 nM have been reported for cAMP and cGMP, respectively (Peracchi et al, ). Assuming that the physiologic extracellular levels are 10–20 μM, the intracellular levels 0.1–10 μM, and that uptake balances efflux at steady state, an iterative method was employed to estimate real K m ‐values for OAT2 uptake of cyclic nucleotides.…”

Section: Methodsmentioning

confidence: 99%

The role of OAT2 (SLC22A7) in the cyclic nucleotide biokinetics of human erythrocytes

Sager

Smaglyukova

Fuskevaag

2018

Journal Cellular Physiology

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The present study was conducted to characterise the transporter(s) responsible for the uptake of cyclic nucleotides to human erythrocytes. Western blotting showed that hRBC expressed OAT2 (SLC22A7), but detection of OAT1 (SLC22A6), or OAT3 (SLC22A8) was not possible. Intact hRBC were employed to clarify the simultaneous cyclic nucleotide egression and uptake. Both these opposing processes were studied. The Km‐values for high affinity efflux was 3.5 ± 0.1 and 39.4 ± 5.7 μM for cGMP and cAMP, respectively. The respective values for low affinity efflux were 212 ± 11 and 339 ± 42 μM. The uptake was characterised with apparently low affinity and similar Km‐values for cGMP (2.2 mM) and cAMP (0.89 mM). Using an iterative approach in order to balance uptake with efflux, the predicted real Km‐values for uptake were 100–200 μM for cGMP and 50–150 μM for cAMP. The established OAT2‐substrate indomethacin showed a competitive interaction with cyclic nucleotide uptake. Creatinine, also an OAT2 substrate, showed saturable uptake with a Km of 854 ± 98 μM. Unexpectedly, co‐incubation with cyclic nucleotides showed an uncompetitive inhibition. The observed Km‐values were 399 ± 44 and 259 ± 30 μM for creatinine, in the presence of cGMP and cAMP, respectively. Finally, the OAT1‐substrate para‐aminohippurate (PAH) showed some uptake (Km‐value of 2.0 ± 0.4 mM) but did not interact with cyclic nucleotide or indomethacin transport.

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“…Before being assayed for cyclic nucleotides plasma was extracted with ethanol as previously described (19). In all subjects dietary sodium intake was unrestricted (120-140 mmol/day) at the time of the study.…”

Section: Patients With Hepatocellular Carcinomamentioning

confidence: 99%

Pattern of Plasma Cyclic Nucleotides and Related Hormones in Liver Cirrhosis and Hepatocellular Cacinoma

Bamonti-Catena

Peracchi²,

Conte³

et al. 1998

CCLM

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To evaluate the pattern of plasma cyclic adenosine 3',5'-monophosphate, cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon levels in different stages of chronic liver diseases, we measured these variables in 20 normal subjects, 25 patients with genetic hemochromatosis, associated with liver cirrhosis in 19 cases and not in six, eight patients with compensated and 15 with decompensated alcoholic or posthepatitic cirrhosis, and 12 with hepatocellular carcinoma. All variables were within the normal range in non-cirrhotic hemochromatotic patients. Cyclic adenosine 3',5'-monophosphate levels were within the normal range (9.5-15.7 nmol/l) in hemochromatotic cirrhotics and elevated in other patients. Cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon were above the normal ranges (1.92-5.91 nmol/l, 8.8-62.7 ng/l, and 39-165 ng/l, respectively) in most patients with cirrhosis both with and without hemochromatosis and in most individuals with hepatocellular carcinoma. Cyclic guanosine 3',5'-monophosphate correlated with atrial natriuretic factor in the former groups but not in the latter. These findings indicate that glucagon and atrial natriuretic factor hypersecretion is an early event in cirrhosis, regardless of its etiology. In hepatocellular carcinoma, the underlying cirrhosis may account for most hormonal and metabolic changes although cyclic guanosine 3',5'-monophosphate increases could also be due to the neoplastic process per se.

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Plasma and urine cyclic nucleotide levels in patients with neoplastic diseases

Cited by 11 publications

References 29 publications

Defects of β₂‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression

Defects of β₂‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression

The role of OAT2 (SLC22A7) in the cyclic nucleotide biokinetics of human erythrocytes

Pattern of Plasma Cyclic Nucleotides and Related Hormones in Liver Cirrhosis and Hepatocellular Cacinoma

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Plasma and urine cyclic nucleotide levels in patients with neoplastic diseases

Cited by 11 publications

References 29 publications

Defects of β2‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression

Defects of β2‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression

The role of OAT2 (SLC22A7) in the cyclic nucleotide biokinetics of human erythrocytes

Pattern of Plasma Cyclic Nucleotides and Related Hormones in Liver Cirrhosis and Hepatocellular Cacinoma

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Defects of β₂‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression

Defects of β₂‐adrenergic signal transduction in chronic lymphocytic leukaemia: relationship to disease progression