scholarly journals MEDIATION OF IMMUNOLOGIC DISCHARGE OF LYSOSOMAL ENZYMES FROM HUMAN NEUTROPHILS BY GUANOSINE 3',5'-MONOPHOSPHATE

1974 ◽  
Vol 140 (1) ◽  
pp. 225-238 ◽  
Author(s):  
L. J. Ignarro ◽  
W. J. George
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Lysosomal Enzymes ◽  
Extracellular Calcium ◽  
Human Neutrophils ◽  
Enzyme Release ◽  
Dibutyryl Cyclic Amp ◽  
Relationship Of ◽  
The Relationship ◽  
Stimulation Of

The purpose of this investigation was to elucidate the relationship of cyclic GMP and calcium to the immunologic discharge of lysosomal enzymes from purified human neutrophils. Contact of neutrophils with a variety of immunologic stimuli, including zymosan particles treated with either normal or rheumatoid arthritic (RA) serum, heat-aggregated (agg) IgG, particulate and immobilized agg IgG each treated with RA serum, and zymosan-treated serum, provoked the discharge of ß-glucuronidase, but not cytoplasmic lactate dehydrogenase, and stimulated the accumulation of cyclic GMP. Both enzyme release and elevation of cyclic GMP levels required the presence of extracellular calcium as neither cellular event proceeded in its absence. Cholinergic enhancement of the immunologic secretion of ß-glucuronidase from neutrophils by acetylcholine was associated with a concomitant accumulation of cyclic GMP. These actions of acetylcholine on neutrophils did not proceed in the absence of extracellular calcium. Whereas the concentrations of cyclic GMP in neutrophils were elevated by both immune reactants and a combination of the latter and acetylcholine, cyclic AMP levels remained unaltered. Thus, cyclic GMP, but not cyclic AMP, was associated with the immunologic and pharmacologic discharge of lysosomal enzymes from neutrophils. Contrariwise, cyclic AMP, but not cyclic GMP, was associated with inhibition of lysosomal enzyme release. For example, dibutyryl cyclic AMP and epinephrine inhibited the release of ß-glucuronidase from neutrophils that was elicited by each of the immune reactants tested. Moreover, cyclic AMP levels in the cells were elevated markedly in every instance that enzyme discharge was inhibited by epinephrine. Epinephrine did not alter the neutrophil concentrations of cyclic GMP at times when those of cyclic AMP were elevated. The data in this report constitute partial evidence that the immunologic discharge of lysosomal enzymes from human neutrophils is mediated or signaled by intracellular cyclic GMP and that calcium is linked to this stimulation of enzyme secretion.

scholarly journals HORMONAL CONTROL OF LYSOSOMAL ENZYME RELEASE FROM HUMAN NEUTROPHILS

1974 ◽  
Vol 139 (6) ◽  
pp. 1395-1414 ◽  
Author(s):  
L. J. Ignarro ◽  
T. F. Lint ◽  
W. J. George
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Lysosomal Enzyme ◽  
Lysosomal Enzymes ◽  
Hormonal Control ◽  
Human Neutrophils ◽  
Cell Contact ◽  
Enzyme Release ◽  
Lactate Dehydrogenase Activity ◽  
Particle Uptake

The purpose of this investigation was to examine the effects of autonomic neurohormones, cyclic nucleotides, and related agents on the immunologic discharge of lysosomal enzymes from, and phagocytosis by, purified human neutrophils. In order to discern the possible intracellular mechanisms by which certain neurohormones influence neutrophil function, the concentrations of cyclic AMP and cyclic GMP in neutrophils were assessed during cell contact with phagocytizable particles and autonomic agents. The model system employed for study was the interaction of purified human neutrophils with rheumatoid arthritic (RA) serum-treated zymosan particles at 37°C in a neutral, balanced salt solution containing glucose. Neutrophils ingested the particles and discharged ß-glucuronidase but not lactate dehydrogenase activity during 30 min of incubation. Treatment of zymosan particles with RA serum was more effective than treatment with normal serum with regard to the extent of both particle uptake and lysosomal enzyme release. During contact of neutrophils with RA serum-treated zymosan particles epinephrine, isoproterenol, and cyclic AMP inhibited both particle ingestion and ß-glucuronidase discharge. These actions of epinephrine were associated with a concomitant elevation of cyclic AMP levels. In contrast to the actions of catecholamines and cyclic AMP, acetylcholine and cyclic GMP accelerated lysosomal enzyme release without affecting particle uptake. The actions of acetylcholine were associated with a concomitant elevation of cyclic GMP levels. Increases in neutrophil levels of cyclic GMP but not of cyclic AMP were associated also with the discharge of ß-glucuronidase provoked by particles in the absence of added cholinergic agents. The data suggest that the immunologic release of lysosomal enzymes from human neutrophils can be regulated by autonomic neurohormones, perhaps via the selective formation of appropriate nucleotides.

CORRELATION OF CYCLIC AMP AND CYCLIC GMP ACCUMULATION AND STEROIDOGENESIS DURING STIMULATION OF BOVINE LUTEAL CELLS WITH LUTEINIZING HORMONE

1980 ◽  
Vol 86 (1) ◽  
pp. 45-52 ◽  
Author(s):  
W. Y. LING ◽  
M. T. WILLIAMS ◽  
J. M. MARSH
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Direct Evidence ◽  
Significant Rise ◽  
Maximum Increase ◽  
Luteal Cells ◽  
Bovine Corpus Luteum ◽  
Intermediary Role ◽  
The Relationship ◽  
Stimulation Of

The relationship between LH-induced steroidogenesis and the production of cyclic AMP and cyclic GMP was studied as a function of LH dose and time in isolated luteal cells from pregnant cows. Submaximal steroidogenic concentrations of LH caused a transient but significant rise in cyclic AMP that peaked after incubation for 5 min. A consequent rise in progesterone occurred at 30 min even though cyclic AMP had returned to the basal level at that time. Higher steroidogenic doses of LH elicited a maximum increase of cyclic AMP at 5 min and this was sustained for up to 1 h; the related progesterone production was significantly raised at 15 min and reached a maximum plateau at 30 min. The corresponding levels of cyclic GMP did not appear to be altered by any of the LH concentrations used. The present study has provided direct evidence that even at very low doses of LH, cyclic AMP plays an intermediary role in the stimulation of steroidogenesis in a mixed population of cells isolated from the bovine corpus luteum. Cyclic GMP, on the other hand, did not appear to play a role in the action of LH on the same population of luteal cells.

Lipolytic response, cyclic AMP and cyclic GMP accumulation in rat adipocytes stimulated with ACTH: Effect of MtT-F4 tumor and clofibrate treatment

1979 ◽  
Vol 57 (7) ◽  
pp. 738-744 ◽  
Author(s):  
C. Gianoulakis ◽  
M. Lis ◽  
M. Chrétien
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Fat Cells ◽  
Dibutyryl Cyclic Amp ◽  
Tumor Bearing ◽  
Tissue Cells ◽  
Adipose Tissue Cells ◽  
Fasted Rats ◽  
Stimulation Of

A hyperlipidemia was induced in male Fisher rats by implantation for 31 days of a mammotropic tumor (MtT-F4) which secretes large quantities of ACTH, GH, and prolactin. Following stimulation of isolated adipose tissue cells with ACTH, the lipolytic response and the accumulation of cyclic AMP were higher in cells derived from the rats with the tumor, while the accumulation of cyclic GMP was not different from control adipocytes. Further, when the isolated adipose tissue cells were stimulated with dibutyryl cyclic AMP the lipolytic response was increased to the same extent in both control and tumor-bearing groups. Clofibrate treatment did not alter the increased lipolytic response though it partially decreased the accumulation of cyclic AMP following stimulation by ACTH in adipocytes derived from tumor-bearing rats. However, clofibrate treatment resulted in a significantly greater accumulation of cyclic GMP in fat cells stimulated with ACTH from both control and tumor-bearing rats. Clofibrate in the diet did not alter the levels of GH or prolactin in the control rats nor were the elevated hormone levels of the tumor-bearing rats changed. Thus the adipose tissue cells from fasted rats treated with clofibrate and treatment withdrawn 24 h prior to sacrifice did not exhibit a decrease in the lipolytic response to ACTH. However, the decrease in the accumulation of cyclic AMP and the increase in the accumulation of cyclic GMP observed may suggest an involvement of these nucleotides in the mechanism of action of clofibrate on the adipose tissue.

Control of brown adipose tissue lipolysis and respiration by adenosine

1983 ◽  
Vol 245 (6) ◽  
pp. E555-E559 ◽  
Author(s):  
D. Szillat ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Palmitic Acid ◽  
Brown Adipose Tissue ◽  
Brown Adipocyte ◽  
Tissue Respiration ◽  
Dibutyryl Cyclic Amp ◽  
Response Curves ◽  
Brown Adipose ◽  
Stimulation Of

Adenosine competitively inhibited the stimulatory effects of (-)-isoproterenol on lipolysis and respiration in hamster brown adipocytes. The low value of the apparent ki for respiratory inhibition by adenosine (7 nM) indicated that the nucleoside may control brown adipocyte function under physiological concentrations. Significantly, the dose-response curves for isoproterenol stimulation of lipolysis and respiration were both shifted by adenosine to higher agonist concentrations by the same order of magnitude, providing additional evidence for a tight coupling between lipolysis and respiration. The inhibitory effects of adenosine were rapidly reversed by a) adenosine deaminase, b) agents known to increase intracellular cyclic AMP levels (isoproterenol, isobutylmethylxanthine, dibutyryl cyclic AMP), and c) direct stimulation of respiration with palmitic acid. These results, combined with the fact that adenosine failed to affect respiration evoked either by dibutyryl cyclic AMP or by palmitic acid, strongly indicate that adenosine regulates brown adipose tissue respiration at an early metabolic step of the stimulus-thermogenesis sequence, most probably at the level of the adenylate cyclase complex.

Mechanism of TSH action. Studies with dibutyryl cyclic AMP and dibutyryl cyclic GMP

FEBS Letters ◽  
1971 ◽  
Vol 13 (6) ◽  
pp. 342-344 ◽  
Author(s):  
V. Macchia ◽  
S. Varrone
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Dibutyryl Cyclic Amp

Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin–pancreozymin

1979 ◽  
Vol 57 (6) ◽  
pp. 541-546 ◽  
Author(s):  
H. L. Cailla ◽  
H. Sarles ◽  
M. V. Singer
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Juice ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Parallel Increase ◽  
Calcium Bicarbonate ◽  
Strong Linear Correlation ◽  
Protein Output ◽  
Dose Dependent ◽  
Stimulation Of

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin–pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg−1 h−1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg−1 h−1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg−1 h−1 of CCK and later for 12 and 24 U kg−1 h−1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.

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