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

1974 ◽  
Vol 52 (4) ◽  
pp. 780-785 ◽  
Author(s):  
T. H. Brian Haig

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.

1981 ◽  
Vol 196 (2) ◽  
pp. 383-390 ◽  
Author(s):  
M J Wakelam ◽  
D G Walker

1. The specificity of the effect of glucose on the induction of glucokinase activity that occurs when hepatocytes freshly isolated from 13-day-old rats are incubated in Medium 199 together with insulin [Wakelam & Walker (1980) FEBS Lett. 111, 115-119] was examined. A pattern that is different from other known effects of glucose is found, and metabolism of this compound is not necessarily to account for this particular effect. 2. The effects of a raised glucose concentration and of insulin on the induction can be separated. The hexose initiates the process in the absence of insulin in a manner that is sensitive to actinomycin D but not to cycloheximide. The subsequent effect of insulin is dependent on the prior effect of glucose or other positive analogue, does not require the presence of glucose and is inhibited by cycloheximide but not by actinomycin D. 3. Induction of glucokinase in vitro in hepatocytes from neonatal animals is inhibited by adrenaline, glucagon and dibutyryl cyclic AMP, but not by vasopressin or angiotensin II. The inhibition by cyclic AMP is on the stage requiring insulin and is comparatively specific, because total protein synthesis is not apparently diminished. 4. The implications of these results are discussed with reference to possible mechanisms of induction and to the situation in vivo.


1976 ◽  
Vol 54 (5) ◽  
pp. 692-697 ◽  
Author(s):  
Seymour Heisler

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.


1979 ◽  
Vol 44 (5) ◽  
pp. 1651-1656 ◽  
Author(s):  
Sixtus Hynie ◽  
Jiří Smrt

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.


Author(s):  
Cecilia Valencia ◽  
Felipe Alonso Pérez ◽  
Carola Matus ◽  
Ricardo Felmer ◽  
María Elena Arias

Abstract The present study evaluated the mechanism by which protein synthesis inhibitors activate bovine oocytes. The aim was to analyze the dynamics of MPF and MAPKs. MII oocytes were activated with ionomycin (Io), ionomycin+anisomycin (ANY) and ionomycin+cycloheximide (CHX) and by in vitro fertilization (IVF). The expression of cyclin B1, p-CDK1, p-ERK1/2, p-JNK, and p-P38 were evaluated by immunodetection and the kinase activity of ERK1/2 was measured by enzyme assay. Evaluations at 1, 4, and 15 hours postactivation (hpa) showed that the expression of cyclin B1 was not modified by the treatments. ANY inactivated MPF by p-CDK1Thr14-Tyr15 at 4 hpa (P < 0.05), CHX increased pre-MPF (p-CDK1Thr161 and p-CDK1Thr14-Tyr15) at 1 hpa and IVF increased p-CDK1Thr14-Tyr15 at 17 hours postfertilization (hpf) (P < 0.05). ANY and CHX reduced the levels of p-ERK1/2 at 4 hpa (P < 0.05) and its activity at 4 and 1 hpa, respectively (P < 0.05). Meanwhile, IVF increased p-ERK1/2 at 6 hpf (P < 0.05); however, its kinase activity decreased at 6 hpf (P < 0.05). p-JNK in ANY, CHX, and IVF oocytes decreased at 4 hpa (P < 0.05). p-P38 was only observed at 1 hpa, with no differences between treatments. In conclusion, activation of bovine oocytes by ANY, CHX, and IVF inactivates MPF by CDK1-dependent specific phosphorylation without cyclin B1 degradation. ANY or CHX promoted this inactivation, which seemed to be more delayed in the physiological activation (IVF). Both inhibitors modulated MPF activity via an ERK1/2-independent pathway, whereas IVF activated the bovine oocytes via an ERK1/2-dependent pathway. Finally, ANY does not activate the JNK and P38 kinase pathways.


Blood ◽  
1969 ◽  
Vol 34 (3) ◽  
pp. 348-356 ◽  
Author(s):  
SEYMOUR WERTHAMER ◽  
CARL HICKS ◽  
LEONARD AMARAL

Abstract The in vitro effects of sterols, cholesterol and 3-methyl cholanthrene and steroids, cortisol, prednisolone and testosterone on protein synthesis in separate popultions of human lymphocytes and leukocytes has been investigated. It has been shown that all agents used result in the inhibition of protein synthesis under these conditions. It has also been shown that the inhibitory mechanism of the steroid hormones requires the presence of plasma, presumably as a protein binding factor in order to achieve its effect. The sterol, cholesterol and 3-methyl cholanthrene, in the absence of plasma, still inhibit amino acid incorporation. However, in the case of cholesterol, the magnitude of inhibition is lower than that observed in the presence of plasma, perhaps indicating a partial plasma dependence. The results presented therefore support the hypothesis that the inhibition of lymphocyte protein synthesis by steroid hormones occurs only when the steroid is bound to a plasma protein. The physiologic role of the plasma protein-cortisol complex and its relation to the condition of lymphopenia in man is discussed.


1976 ◽  
Vol 71 (2) ◽  
pp. 231-238 ◽  
Author(s):  
RÉGINE PICON

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.


Reproduction ◽  
1989 ◽  
Vol 86 (1) ◽  
pp. 373-381 ◽  
Author(s):  
B. K. Tsang ◽  
D. F. Mattice ◽  
M. Li ◽  
E. K. Asem

Development ◽  
1987 ◽  
Vol 100 (4) ◽  
pp. 599-609
Author(s):  
J.-C. Beetschen ◽  
J. Gautier

Axolotl eggs were heat shocked (36.8°C, 10min) inside their jelly layers. Heat shock (HS) was shown to induce the precocious appearance of a grey crescent (GC) in a number of eggs immediately after fertilization (Benford & Namenwirth, 1974). It was also demonstrated that this phenomenon occurs in fertilized or artificially activated eggs only when they are shocked within 11/2h after spawning. The GC forms still later in heated unfertilized, nonactivated eggs. The role of the jelly layers is considered to be mechanical: a proportion of eggs is maintained in a tilted position until the egg is able to orient animal pole upwards under the influence of gravity as a late consequence of activation. The jelly layers are not essential if the eggs are artificially tilted or rotated during HS. GC formation can also be induced in in vitro maturing oocytes, provided they are tilted during HS. Gravity thus plays an essential role in the cytoplasmic rearrangements leading to HS-induced GC formation. Our results indicate a synergistic action between heat and gravity in this process. The cytological appearance of the GC formed in those experiments is that of a ‘Born's crescent’ with a conspicuous ‘vitelline wall’ (Pasteels, 1964). When oocytes are enucleated before maturation, HS has no effect on GC formation. A nuclear factor is therefore essential, as has been demonstrated in early GC formation induced by inhibitors of protein synthesis. Finally, incorporation of amino acids into oocyte proteins appears to be rapidly inhibited by HS (from 5 min). However, we cannot conclude that GC formation is in fact triggered by inhibition of protein synthesis. It is also likely that HS disrupts cytoskeletal structure, hence facilitating cytoplasmic rearrangements. Nevertheless, these results are in agreement with the scheme we recently proposed for GC formation in the rotated axolotl oocyte (Gautier & Beetschen, 1985).


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