Antagonistic influences of dibutyryl cyclic AMP and dibutyryl cyclic GMP on the beating rate of cultured mouse myocardial cells

The involvement of cyclic AMP in the settlement of the cypris larva of Balanus amphitrite amphitrite Darwin has been examined through the use of compounds that affect intracellular cyclic AMP levels. The activation of adenylate cyclase with forskolin, and the inhibition of phosphodiesterase with 3-isobutyl-1-methylxanthine, caffeine and theophylline, significantly increased the settlement of cyprids. Although the analogue dibutyryl cyclic AMP appeared to increase settlement, the effect was not significant. No marked increase in settlement resulted from the incubation of cyprids with dibutyryl cyclic GMP, 8-(4-chlorophenylthio) (CPT) cyclic AMP or papaverine (a phosphodiesterase inhibitor). Miconazole nitrate, an adenylate cyclase inhibitor, prevented settlement, but this effect appeared to be physico-chemical rather than pharmacological. Radioimmunoassay did not clearly show whether cyclic AMP levels changed following exposure of cyprids to a pulse of crude barnacle extract. However, exposure to forskolin significantly increased the cyclic AMP titre of cyprids. We conclude that compounds that alter intracellular cyclic AMP levels alter normal patterns of cyprid settlement. Whether this is because of an alteration in signal transduction is unclear.

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

Journal of Experimental Medicine ◽

10.1084/jem.140.1.225 ◽

1974 ◽

Vol 140 (1) ◽

pp. 225-238 ◽

Cited By ~ 48

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.

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Effects of an ATP analogue (α,β-methylene-adenosine-5′-triphosphate) on cyclic AMP and cyclic GMP levels, 45Ca efflux, and protein secretion from rat pancreas

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y76-096 ◽

1976 ◽

Vol 54 (5) ◽

pp. 692-697 ◽

Cited By ~ 3

Author(s):

Seymour Heisler

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Calcium Ionophore ◽

Competitive Inhibitor ◽

The Other ◽

Dibutyryl Cyclic Amp ◽

Onset Of Action ◽

Rat Pancreas ◽

A 23187

The effects of the α,β-methylene analogue of ATP (Ap(CH2)pp), described as a competitive inhibitor of adenylate cyclase (EC 4.6.1.1), were studied in the rat pancreas in vitro. The analogue did not alter basal cyclic AMP production and basal or carbachol-stimulated efflux of 45Ca from isotope-preloaded glands. On the other hand, Ap(CH2)pp reduced the secretory responses to carbachol, carbachol in the presence of dibutyryl cyclic AMP, pancreozymin (PZ), and the calcium ionophore, A-23187. Release of pancreatic protein in response to dibutyryl cyclic AMP itself was unaffected by the ATP analogue, suggesting that the other secretagogues tested share a common, Ap(CH2)pp-inhibitable pathway in their respective stimulatory actions. Though carbachol, PZ, and A-23187 all stimulated a rapid production (30 s) of pancreatic cyclic GMP, these responses were not affected by Ap(CH2)pp. Additional studies with the analogue indicated that it has a slow onset of action (30–45 min), i.e., its effect on secretion is preceded by secretagogue-induced changes in nucleotide levels and calcium efflux. Nonetheless, the analogue may affect cellular calcium homeostasis, if not during the initial events triggering secretion, then during those events which maintain continued secretory output in the presence of a stimulus.

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Lactic acid and steroid production by intact mouse adrenal glands and cell suspensions: effects of nucleotide derivatives and substrates

Journal of Endocrinology ◽

10.1677/joe.0.1040105 ◽

1985 ◽

Vol 104 (1) ◽

pp. 105-111 ◽

Cited By ~ 3

Author(s):

J. Hinson ◽

M. K. Birmingham

Keyword(s):

Lactic Acid ◽

Cyclic Amp ◽

Cyclic Gmp ◽

Acid Production ◽

Adrenal Glands ◽

Lactic Acid Production ◽

Cell Suspensions ◽

Dibutyryl Cyclic Amp ◽

Steroid Production ◽

Intact Mouse

ABSTRACT The effects of the dibutyryl derivatives of cyclic GMP and cyclic AMP on lactic acid and steroid production were compared in intact mouse adrenal glands at concentrations of 0·5–1 mmol/l and in mouse adrenal cell suspensions at concentrations of 0·01–1 mmol/l. The dibutyryl derivative of cyclic GMP had little or no effect on lactic acid production in either tissue preparation. It caused a slight stimulation of corticosteroid output in intact glands at a concentration of 1 mmol/l, amounting to one-tenth of the response observed with 1 mm-dibutyryl cyclic AMP. Dose-dependent increases in lactic acid and steroid production were obtained with dibutyryl cyclic AMP in cell suspensions. AMP and GMP increased lactic acid but not steroid production. All the substrates tested (glucose, glucose-6-phosphate, fructose, fructose-6-phosphate, fructose-1,6-diphosphate, 10 mmol/l; pyruvate and glycerol, 20 mmol/l) stimulated basal glycolysis in intact glands and cell suspensions and none affected basal steroid production significantly. By far the greatest increase in lactic acid production was noted with fructose-1,6-diphosphate. However, only glucose and, in unsectioned glands, pyruvate exerted a potentiating effect on the glycolytic response to ACTH. Glucose potentiated the steroidogenic response to ACTH also, but only in intact glands. The relative ineffectiveness of dibutyryl cyclic GMP is in accord with the species-dependent differing responses to the free form of the cyclic nucleotides noted in mouse and rat adrenal glands. The substrate requirements are in keeping with a rate-limiting role of phosphofructokinase and an action of ACTH at some site between the entry of glucose into the cell and the formation of fructose-1,6-diphosphate. J. Endocr. (1985) 104, 105–111

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ABILITY OF VARIOUS FACTORS TO OPPOSE THE STIMULATORY EFFECT OF DIBUTYRYL CYCLIC AMP ON THE RELEASE OF MELANOCYTE-STIMULATING HORMONE BY THE RAT PITUITARY IN VITRO

Journal of Endocrinology ◽

10.1677/joe.0.0680283 ◽

1976 ◽

Vol 68 (2) ◽

pp. 283-287 ◽

Cited By ~ 5

Author(s):

BRIDGET I. BAKER

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Inhibitory Effect ◽

Aminobutyric Acid ◽

Intermediate Lobe ◽

Dibutyryl Cyclic Amp ◽

Melanocyte Stimulating Hormone ◽

Rat Pituitary ◽

Stimulating Hormone

SUMMARY Various agents were tested for their ability to oppose the stimulatory effect of dibutyryl cyclic AMP on the release of the melanocyte-stimulating hormone from the rat neuro-intermediate lobe in vitro. Only dopamine exhibited an inhibitory effect; serotonin, γ-aminobutyric acid, tocinoic acid, tocinamide, the tripeptide Pro-Leu-Gly-NH2 and dibutyryl cyclic GMP were all ineffective.

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