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

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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Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665317 ◽

1983 ◽

Vol 50 (04) ◽

pp. 804-809 ◽

Cited By ~ 16

Author(s):

Torstein Lyberg

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Immune Complexes ◽

Phosphodiesterase Inhibitors ◽

Inhibitory Effect ◽

Intracellular Camp ◽

Human Monocytes ◽

Purified Protein Derivative ◽

A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

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Is Phospholipase A2 (PLA2) Involved In PAF-Acether Formation By Platelets

10.1055/s-0038-1652801 ◽

1981 ◽

Author(s):

M Chignard ◽

B B Vargaftig ◽

J P Le Couedic ◽

J Benveniste

Keyword(s):

Arachidonic Acid ◽

Cyclic Amp ◽

Chelating Agents ◽

Creatine Phosphokinase ◽

Platelet Activating Factor ◽

Calcium Ionophore ◽

Adenosine Diphosphate ◽

Creatine Phosphate ◽

Dibutyryl Cyclic Amp ◽

A 23187

PAF-acether (platelet-activating factor) has been recently identified as l-O-alkyl-2-acetyl-sn-glyceryl-phosphorylcholine, and later chemically synthetized. Platelets form PAF-acether upon stimulation with the calcium ionophore A 23187 or with more physiological stimuli such as thrombin or collagen. By contrast, arachidonic acid (AA) and adenosine diphosphate (ADP) do not trigger formation of PAF-acether. Since 1) PAF-acether is a phospholipid derivative and 2) aggregating agents which trigger PAF-acether formation are potent platelet PLA2 stimulators, we speculated that PLA2 could be implicated in its formation.Rabbit washed platelets were incubated at 37°C in the presence of thrombin (2.5 U/ml) or of ionophore A 23187 (2.5 uM) for 7 min and ethanol (80 % final) was added. After centrifugation, the supernatant was evaporated and concentrated. The extract was tested for its aggregating property on rabbit washed platelets preincubated with a cyclo-oxygenase inhibitor (aspirin) and an ADP scavenging system (creatine phosphate and creatine phosphokinase).In the presence of calcium chelating agents such as EDTA (5 mM) and EGTA (5 mM) most of the synthesis of PAF-acether was suppressed (93 % and 100 % of inhibition respectively). Dibutyryl cyclic AMP (5 mM) also suppressed PAF-acether formation from platelets challenged by thrombin or by the ionophore A 23187 (100 % and 62 % inhibition respectively). Bromophenacyl bromide (0.1 mM) and compound CB 874 (0.1 mM) proved also to be very potent inhibitors of PAF-acether synthesis (100 % inhibition both). All these drugs are well-known platelet PLA2 inhibitors. Upon stimulation platelets also form a deacetylated PAF-acether (lyso- PAF-acether) which could be the direct precursor of PAF-acether. The release of lyso-PAF-acether and the blockade of PAF-acether formation by various molecules having in common a PLA- inhibitory activity lead us to conclude that a PLA2 may be implicated in PAF-acether formation from platelets. Alternative explanations include the possibility that the various inhibitors act on other membrane-related sites.

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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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Regulation of Pancreatic Acinar Function: Effects of Cyclic AMP, Dibutyryl Cyclic AMP, and Theophylline in Vitro

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y74-102 ◽

1974 ◽

Vol 52 (4) ◽

pp. 780-785 ◽

Cited By ~ 7

Author(s):

T. H. Brian Haig

Keyword(s):

Protein Synthesis ◽

Cyclic Amp ◽

Digestive Enzymes ◽

Amylase Secretion ◽

Dibutyryl Cyclic Amp ◽

Rat Pancreas ◽

Rule Out

The role of cyclic AMP in the regulation of pancreatic acinar function has been assessed by measuring the effects of exogenous cyclic AMP, dibutyryl cyclic AMP, and theophylline on protein synthesis and amylase secretion. The rate at which slices of rat pancreas incorporated leucine into protein did not change as a consequence of treatment with either cyclic AMP or dibutyryl cyclic AMP, nor did the slices alter their rate of amylase secretion. Moreover, theophylline did not enhance the ability of submaximal doses of pancreozymin to stimulate amylase secretion or to suppress protein synthesis. These results fail to demonstrate that cyclic AMP regulates either the synthesis or secretion of pancreatic digestive enzymes but they do not rule out the possibility.

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Comparison of protocols for cryopreservation of rhesus monkey spermatozoa by post-thaw motility recovery and hyperactivation

Reproduction Fertility and Development ◽

10.1071/rd06019 ◽

2006 ◽

Vol 18 (7) ◽

pp. 777 ◽

Cited By ~ 5

Author(s):

S. M. Nichols ◽

B. D. Bavister

Keyword(s):

Statistical Analysis ◽

Cyclic Amp ◽

Rhesus Macaques ◽

The Other ◽

In Vitro Fertilisation ◽

Dibutyryl Cyclic Amp ◽

Atmospheric Air ◽

Cryopreservation Techniques ◽

Over Time

Cryopreservation of spermatozoa is useful for gene banking and for in vitro fertilisation (IVF). This study compared several published cryopreservation techniques to find the most efficient for rhesus macaques. Effectiveness was assessed by sperm longevity (post-thaw motility % and duration) and ability to hyperactivate in response to chemical activators (caffeine, dibutyryl cyclic AMP). Each ejaculate from three males was treated with four published cryopreservation protocols (Seier et al. 1993; Sanchez-Partida et al. 2000; Si et al. 2000; Isachenko et al. 2005). Upon thawing, each sub-sample was incubated either at 37°C in 5% CO2 in air with or without activators or at ~22°C in atmospheric air without activators for 0–24 h. Samples cryopreserved using one method showed zero motility and were not included in the 2 × 2 G-test statistical analysis. The other methods all demonstrated good immediate post-thaw motility rates (68%, 73% and 62% respectively) and underwent capacitation after exposure to activators. Sperm motility in each treatment decreased over time at both temperatures but overall, incubation at 22°C preserved motility better in all three methods. In summary, cryopreservation of rhesus spermatozoa using the method published by Sanchez-Partida et al. or Seier et al. appeared best, potentially supporting gene banking as well as allowing for multiple IVF uses from the same sample.

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The inhibitory effects of some adenosine nucleolipids on the lipolysis in rat epididymal fat pads in vitro

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19791651 ◽

1979 ◽

Vol 44 (5) ◽

pp. 1651-1656 ◽

Cited By ~ 2

Author(s):

Sixtus Hynie ◽

Jiří Smrt

Keyword(s):

Fatty Acids ◽

Cyclic Amp ◽

Dibutyryl Cyclic Amp ◽

Inhibitory Effects ◽

Epididymal Fat ◽

Fat Pads

3'-Oleolyl-2,3-dihydroxypropyl-AMP, 3'-stearoyl-2,3-dihydroxypropyl-AMP, octadecyl-AMP and palmitamidoethyl-AMP inhibited in comparison with adenosine or fatty acids much stronger the lipolysis in rat epididymal fat pads in vitro stimulated by isoproterenol, theophylline and dibutyryl cyclic AMP. The inhibition of the effects of the two latter drugs suggest that the described effect is caused not only by the inhibition of the cyclic AMP production but also by the inhibition of its effect on the following steps in process of lipolysis.

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

Journal of Molecular and Cellular Cardiology ◽

10.1016/0022-2828(76)90013-4 ◽

1976 ◽

Vol 8 (9) ◽

pp. 713-725 ◽

Cited By ~ 13

Author(s):

K Goshima

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Myocardial Cells ◽

Dibutyryl Cyclic Amp ◽

Beating Rate

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TESTOSTERONE SECRETION BY FOETAL RAT TESTES IN VITRO

Journal of Endocrinology ◽

10.1677/joe.0.0710231 ◽

1976 ◽

Vol 71 (2) ◽

pp. 231-238 ◽

Cited By ~ 67

Author(s):

RÉGINE PICON

Keyword(s):

Cyclic Amp ◽

Synthetic Medium ◽

Functional Differentiation ◽

Dibutyryl Cyclic Amp ◽

Testosterone Secretion ◽

Testosterone Production ◽

Foetal Rat

SUMMARY Testosterone secretion by foetal rat testes (13½–21½ days of gestation) explanted for 3 days in a synthetic medium was measured every 24 h by radioimmunoassay. During the first day of explantation, the foetal testis produced, respectively, 1013 ± 132, 8734 ± 1118, 9179 ± 2185 and 3886 ± 309 (s.e.m.) pg/testis when explanted at 14½, 16½, 18½ and 21½ days respectively. Testosterone production by 13½-day-old testes was not detectable on the first day of culture, but appeared on subsequent days. Daily testosterone secretion increased on the 2nd and 3rd days of culture in 14½-day-old testes and decreased in older stages. These results suggest that the functional differentiation of the testis is independent of stimulatory factors like gonadotrophins. Dibutyryl cyclic AMP was found to stimulate testosterone production significantly from 14½ days of gestation onwards.

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