Patterns of cyclic nucleotides in normal and leukaemic human leucocytes

Abstract

Summary.-Because recent observations indicate that metabolism of cyclic nucleotides may be altered in neoplastic cells, the intracellular levels of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) were measured in mononuclear leukaemic and normal human leucocytes. The activities of adenylate cyclase, guanylate cyclase and cyclic nucleotide phosphodiesterases were also determined. Under basal conditions, cAMP levels were always higher in the normal leucocytes, whilst cGMP levels were of the same order of magnitude in both normal and leukaemic cells, causing the cAMP/cGMP ratios to be significantly lower in leukaemic leucocytes. Leukaemic cells significantly increased cyclic nucleotide levels in response to theophylline, but did not respond to serotonin, carbamylcholine or D,L-isoproterenol. Preincubation of these leucocytes with theophylline produced a detectable cAMP response to D,L-isoproterenol but no cGMP response to serotonin or carbamylcholine was found. Adenylate cyclase and guanylate cyclase were significantly lower in leukaemic than in normal cells, which could largely explain the abnormal cyclic nucleotide pattern found in human leukaemic leucocytes. In our experiments, cAMP phosphodiesterase activity was comparable in normal and leukaemic cells, whereas cGMP phosphodiesterase activity was undetectable in all mononuclear-leucocyte preparations with the methods used.

Plasma cyclic nucleotide levels in patients with homozygous beta‐thalassaemia

“…In agreement with the hypothesis that cyclic adenosine 3', 5'-monophosphate (CAMP) and cyclic guanosine 3', 5'-monophosphate (cGMP) play a role in the control of cell growth and differentiation (1)(2)(3)(4), alterations in cyclic nucleotide metabolism have often been found in neoplastic tissues (5)(6)(7)(8)(9)(10)(11). Recently, alterations in extracellular cyclic nucleotide levels have also been reported in human malignancies.…”

Effect of high doses of somatostatin on adenylate cyclase activity in peripheral mononuclear leukocytes from normal subjects and from acute leukemia patients

“…However, control validity constitutes a major problem in the -<. evaluation of cAMP metabolism in human acute leukemia blasts since at present normal human lymphoblasts and myeloblasts are not available for study 15. With this limitation in mind, our results confirm that under basal conditions a low adenylate cyclase activity characterizes both ALL and ANLL cells which also show a markedly decreased responsiveness to isoproterenol, probabl}r due to a reduction in adrenergic receptors ~ 3.…”

Duodenal mucosa and extracellular cyclic nucleotide pattern in coeliac disease.

“…from control subjects and in those from coeliac 'rom four control subjects (@),five untreated ase patients (-), and three treated coeliac disease disease patients who had been treated. In homogenates from coeliac disease patients who had not been treated peptide concentrations of [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] [tg/ml failed to increase adenylate cyclase E ASSAYS AND BIOCHEMISTRY activity consistently, whereas concentrations of glucagon and atrial natriuretic peptide 50-200 [tg/ml all stimulated the enzyme to the rere measured by double antibody RIA same degree (Figure). Basal guanylate cyclase using commercially available kits activity was lower in homogenates from coeliac Antibody Glucagon, Diagnostic disease patients who had not been treated than in Corporation, Los Angeles, CA, USA; those from patients who had been treated and Atrial Natriuretic Peptide, Immuno from control subjects, though the differences ogy Service Production BV, Wijchen, were not statistically significant (Table I).…”