THE EFFECT OF DIBUTYRYL CYCLIC ADENOSINE‐3′,5′‐MONOPHOSPHATE ON PROTEIN SECRETION FROM THE RAT EXOCRINE PANCREAS <i>in vitro</i>

Fast, Diane K.; Tenenhouse, Alan

doi:10.1111/j.1476-5381.1976.tb08630.x

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…Moreover, dibutyryl cyclic AMP potentiated the effect of the ionophore on amylase secretion and stimulated efflux of 45Ca from pancreatic fragments. The latter observation was at variance with results obtained by Fast & Tenenhouse (1976). The difference between their observations and the present results could be methodological.…”

Section: Resultscontrasting

confidence: 56%

“…The difference between their observations and the present results could be methodological. In the present study, efflux was determined after extracellular 45Ca was washed out from the preloaded fragments (see Case & Clausen, 1973) whereas Fast & Tenenhouse (1976) studied 45Ca efflux directly after loading the tissue. Using the latter method in our laboratory, dibutyryl cyclic AMP was found to inhibit 45Ca efflux for the first 40 min and a combination of dibutyryl cyclic AMP with A23187 did not result in abolition of A23187-induced efflux (M. Singh, unpublished observations).…”

Section: Resultsmentioning

confidence: 99%

“…It has been suggested that the effect of cyclic AMP may be mediated through conservation of secretagogue mobilized Ca2+ at a site at which enzyme secretion was triggered (Heisler et al 1974;Fast & Tenenhouse, 1976). This was not borne out by the results of the present study.…”

Section: Resultsmentioning

confidence: 99%

“…A number of investigators have studied the role of Ca2+ (Case & Clausen, 1973;Matthews et al 1973;Gardner et al 1975;Williams & Chandler, 1975) and of cyclic nucleotides (by studying the interaction of octapeptide of porcine cholecystokinin (CCK-OP) or carbamylcholine with secretin, VIP and dibutyryl cyclic AMP and of secretin or VIP by CCK-OP, carbamylcholine, or dibutyryl cyclic GMP, see Gardner & Jackson (1977)). Dibutyryl cyclic AMP was reported to potentiate the effect of secretagogues in rat pancreas by inhibiting Ca2+ efflux thus maintaining an elevated intracellular Ca2+ concentration (Fast & Tenenhouse, 1976). Heisler & Lambert (1978) reported dissociation between the synthesis of cyclic GMP and secretary response to carbachol when the extracellular Ca2+ concentration was lowered to 0 05 mm.…”

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confidence: 99%

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Calcium and cyclic nucleotide interaction in secretion of amylase from rat pancreas in vitro.

Singh¹

1979

The Journal of Physiology

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SUMMARY1. Interaction of Ca2+ and cyclic nucleotides in stimulus-secretion coupling in rat pancreas in vitro was studied utilizing the divalent cation inophore A23187. phosphodiesterase inhibitors, cyclic nucleotides and cholera toxin.2. Amylase secretion was increased by the ionophore in the presence of extracellular Ca2+ in a dose-dependent fashion. Activation of CCK-PZ receptors simultaneously with induction of amylase secretion by A23187 did not alter amylase secretion whereas theophylline or caffeine had effects additive to A23187. Dibutyryl cyclic AMP potentiated the effect of ionophore whereas dibutyryl cyclic GMP had no effect on basal or ionophore-induced amylase secretion. Cholera toxin by itself did not effect amylase secretion whereas it potentiated the effect ofionophore.3. A23187 increased bidirectional fluxes of 45Ca and increased efflux of 45Ca in a fashion similar to CCK-PZ. Theophylline did not alter basal efflux of 45Ca. Dibutyryl cyclic AMP increased the basal efflux of 45Ca whereas, cholera toxin, dibutyryl cyclic GMP and sodium butyrate had no effect.4. Theophylline increased basal cyclic AMP levels with a peak effect observed at 5 min. Combination of theophylline and ionophore did not lead to an increase in levels of cyclic AMP greater than that observed with theophylline alone. Cholera toxin increased cyclic AMP levels at 30 and 60 min of incubation.5. Ionophore and CCK-PZ increased tissue cyclic GMP levels significantly greater than that obtained with theophylline alone. This effect was dependent on extracellular Ca2+. The effect of ionophore on tissue levels of cyclic GMP could be dissociated from its effect on 45Ca efflux and amylase secretion.6. It is concluded from these studies that Ca2+ plays a predominant role in regulating amylase secretion with interactions occurring between Ca2+ and cyclic AMP and Ca2+ and cyclic GMP. It appears that by themselves cyclic AMP and cyclic GMP do not play a significant role in regulating enzyme secretion.

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Section: Resultscontrasting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Calcium and cyclic nucleotide interaction in secretion of amylase from rat pancreas in vitro.

Singh¹

1979

The Journal of Physiology

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“…Ionophore A23187 acts at the plasma membrane of cells to increase influx of extracellular Ca2+ (Foreman, Mongar & Gomperts, 1973;Cochrane & Douglas, 1974; Charles, Lawecki, Pictet & Grodsky, 1975; Cochrane, Douglas, Mouri & Nakazato, 1975;Garcia, Kirpekar & Prat, 1975) and has been used to study the role of Ca2+ and cyclic nucleotides in stimulus-secretion coupling in pancreatic acinar cells (Eimerl, Savion, Heichal & Selinger, 1974;Christophe et al 1976;Fast & Tenenhouse, 1976;Heisler, 1976;Schreurs et al 1976;Williams et al 1977;Heisler & Lambert, 1978;Singh, 1979). Introduction of Ca2+ into acinar cells by ionophore A23187 stimulates amylase secretion (Eimerl et al 1974;Williams & Lee, 1974;Christophe et al 1976;Schreurs et al 1976; Singh, 1979) indicating that a rise in intracellular Ca2+ is of critical importance in digestive enzyme secretion.…”

Section: Introductionmentioning

confidence: 99%

Stimulus‐secretion coupling in rat pancreas: role of sodium, calcium and cyclic nucleotides studied by X‐537A and BrX‐537A.

Singh¹

1980

The Journal of Physiology

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SUMMARY1. The aim of the present work was to study the role of Na+, Ca2+ and cyclic nucleotides in stimulus-secretion coupling in rat pancreatic acinar cells utilizing Ca2+ specific ionophore A23187 as well as ionophores X-537A and BrX-537A which transport both monovalent and divalent cations across biological membranes.2. X-537A, BrX-537A and A23187 increased amylase secretion by a direct energy dependent action without damaging the cells. Antimycin-A and dinitrophenol increased the spontaneous release of amylase.3. In the absence of extracellular Ca2+, the secretary response to X-537A and BrX-537A was reduced by 57 and 50 % respectively whereas A23187 was without effect. In the absence of extracellular Na+, both basal and ionophore stimulated secretion of amylase were increased. Replacement of Na+ by Li+ or Tris+ in Ca2+-free medium abolished the increase in amylase secretion.4. X-537A increased bidirectional flux of uCa2+. Efflux of 45Ca2+ persisted in Ca2+-free media. In Tris-Ringer and Li-Ringer, basal 45Ca2+ influx and amylase secretion were increased. Moreover X-537A enhanced both 45Ca2+ efflux and amylase secretion. This effect was abolished in media containing no Na+ and Ca2+ suggesting that Na+ concentration gradient across the membrane is critical for digestive enzyme secretion.5. Theophylline increased basal concentration of cyclic-GMP at 1, 2, 5, 15 and 30 min. X-537A stimulated cyclic-GMP synthesis in presence of theophylline with a peak effect observed at 15 min with X-537A. Incubation of pancreatic fragments in Ca2+-free media containing EGTA (5 x 10-5 M) decreased basal and X-537A stimulated synthesis of cyclic-GMP.6. From these data it is concluded that Na+ plays a direct role in Ca2+ mobilization and exocytosis. Like other tissues, cyclic-GMP synthesis is dependent on extracellular Ca2+ and does not seem to play a role in stimulus-secretion coupling.

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Stimulus secretion coupling: Role of cyclic GMP and calcium in the regulation of secretion from rat exocrine pancreas

Rochette‐Egly

Launay

Grenier

1980

Journal Cellular Physiology

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In rat pancreatic fragments, stimulation of amylase and labeled protein release by carbachol, caerulein, and ionophore A 23187 results within minutes in a short rise in cyclic GMP levels. Cyclic AMP levels do not change significantly. The secretory response elicited by each secretagogue is not modified when combined in pairs. Under intracellular calcium depleting conditions, both the cyclic GMP and the secretory responses to secretagogues are inhibited in parallel, suggesting a good correlation between both processes. Furthermore, 8-Bromocyclic GMP induces pancreatic secretion, but to a lesser extent, and fails to alter the increase in secretion caused by the various secretagogues. However, other agents such as imidazole, ascorbic acid, phenylhydrazine, and sodium azide also increase cyclic GMP levels but fail to stimulate pancreatic secretion. On the other hand, dibutyryl cyclic AMP also stimulates amylase and labeled protein discharge and potentiates the increase caused by cabachol, caerulein, and ionophore A 23187. These results do not permit conclusions regarding a cause and effect relationship between cyclic GMP and secretion. A role for calcium seems to be the most likely.

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THE EFFECT OF DIBUTYRYL CYCLIC ADENOSINE‐3′,5′‐MONOPHOSPHATE ON PROTEIN SECRETION FROM THE RAT EXOCRINE PANCREAS in vitro

Cited by 9 publications

References 20 publications

Calcium and cyclic nucleotide interaction in secretion of amylase from rat pancreas in vitro.

Calcium and cyclic nucleotide interaction in secretion of amylase from rat pancreas in vitro.

Stimulus‐secretion coupling in rat pancreas: role of sodium, calcium and cyclic nucleotides studied by X‐537A and BrX‐537A.

Stimulus secretion coupling: Role of cyclic GMP and calcium in the regulation of secretion from rat exocrine pancreas

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