Effect of A23187 on amylase release from dispersed acini prepared from guinea pig pancreas

Gardner, J. D.; Walker, Michael D.; Rottman, Alvin J.

doi:10.1152/ajpgi.1980.238.5.g458

Cited by 6 publications

(4 citation statements)

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“…It is possible that stimulation of pancreatic secretion, in at least mouse and guinea pig, is primarily under the control of a single regulatory pathway. In guinea-pig pancreatic acini, TPA alone elicits a full secretory response, whereas the response to A23187 is about 33 % ofmaximum (Gardner et al, 1980;Gunther, 1981; the present paper); in mouse acini the secretory response to TPA is 28 % of maximum, whereas A23187 elicits a much larger response, close to that induced by carbamoylcholine (Williams et al, 1978; the present paper). Although the substrates of protein kinase C and Ca2+-activated phosphorylation enzymes (i.e.…”

Section: U-supporting

confidence: 51%

Regulation of protein phosphorylation in pancreatic acini. Distinct effects of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate

Burnham¹,

Munowitz²,

Hootman³

et al. 1986

Biochemical Journal

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Regulation of protein phosphorylation in isolated pancreatic acini by the intracellular messengers Ca2+ and diacylglycerol was studied by using the Ca2+ ionophore A23187 and the tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate. As assessed by two-dimensional polyacrylamide-gel electrophoresis, the phorbol ester (1 microM) and Ca2+ ionophore (2 microM) altered the phosphorylation of distinct sets of proteins between Mr 83,000 and 23,000 in mouse and guinea-pig acini. The phorbol ester increased the phosphorylation of four proteins, whereas the ionophore increased the phosphorylation of two proteins and, in mouse acini, decreased the phosphorylation of one other protein. In addition, the phorbol ester and ionophore each caused the dephosphorylation of two proteins, of Mr 20,000 and 20,500. Administered together, these agents reproduced the changes in phosphorylation induced by the cholinergic agonist carbamoylcholine. The effects of the phorbol ester and ionophore on acinar amylase release were also studied. In mouse pancreatic acini, a maximally effective concentration of phorbol ester (1 microM) produced a secretory response that was only 28% of that produced by a maximally effective concentration of carbamoylcholine, whereas the ionophore (0.3 microM) stimulated amylase release to two-thirds of the maximal response to carbamoylcholine. In contrast, in guinea-pig acini, the phorbol ester and carbamoylcholine evoked similar maximal secretory responses, whereas the maximal secretory response to the ionophore was only 35% of that to carbamoylcholine. Combination of phorbol ester and ionophore resulted in a modest synergistic effect on amylase release in both species. It is concluded that cholinergic agonists act via both diacylglycerol and Ca2+ to regulate pancreatic protein phosphorylation, but that synergism between these intracellular messengers is of limited importance in stimulating enzyme secretion.

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Section: U-supporting

confidence: 51%

Regulation of protein phosphorylation in pancreatic acini. Distinct effects of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate

Burnham¹,

Munowitz²,

Hootman³

et al. 1986

Biochemical Journal

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“…To test this proposition, we measured the effect of the Ca ++ ionophore A2318"/ on amylase discharge and 45Ca++ efflux. A23187 bypasses cell surface receptors to trigger protein secretion from adult pancreas, presumably by increasing the [Ca÷+]c via mobilization of intracellular Ca ++ stores and/or increasing Ca ++ influx from the extracellular medium (6,11,15,19,35). Fig.…”

Section: Effect Of A23187 Alone and In Combination With Dbcamp Or Phorbol Dibutyrate On 45ca++ Efflux And Amylase Discharge In Pancreaticmentioning

confidence: 99%

Stimulus-secretion coupling in the developing exocrine pancreas: secretory responsiveness to cholecystokinin.

Chang¹,

Jamieson²

1986

The Journal of Cell Biology

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Abstract. We have studied the onset of secretory responsiveness to cholecystokinin (CCK) during development of the rat exocrine pancreas. Although acinar cells of the fetal pancreas (1 d before birth) are filled with zymogen granules containing the secretory protein, a-amylase, the rate of amylase secretion from pancreatic lobutes incubated in vitro was not increased in response to CCK. In contrast, the rate of CCKstimulated amylase discharge from the neonatal pancreas (1 d after birth) was increased four-to eightfold above that of the fetal gland. The postnatal amplification of secretory responsiveness was not associated with an increase in the number or cell surface expression of ~zsI-CCK binding sites. When 125I-CCK-33 binding proteins were analyzed by affinity crosslinking, two proteins of Mr 210,000 and 100,000-160,000 were labeled specifically in both fetal and neonatal pancreas. To determine if cell surface receptors for CCK in the fetal pancreas are functional and able to generate a rise in the cytosolic [Ca++], we measured 4sCa÷* et~ux from tracer-loaded lobules. 45Ca++ efllux from both fetal and neonatal pancreas was comparably increased by CCK, indicating CCKinduced Ca ÷+ mobilization and elevated cytosolic [Ca÷÷]. The Ca ++ ionophore A23187 also stimulated the rate of 45Ca++ extrusion from pancreas of both ages. Increased amylase secretion occurred concurrently with A23187-stimulated 45Ca++ efflux in neonatal pancreas, but not in the fetal gland. A23187 in combination with dibutyryl cAMP potentiated amylase release from the neonatal gland, but not from fetal pancreas. Similarly, the protein kinase C activator, phorbol dibutyrate, did not increase the rate of secretion from the fetal gland when added alone or in combination with A23187 or CCK. We suggest that CCK-receptor interaction in the fetal pancreas triggers intracellular Ca ++ mobilization. However, one or more signal transduction events distal to Ca +÷ mobilization have not yet matured. The onset of secretory response to CCK that occurs postnatally may depend on amplification of these transduction events.

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“…In other gastrointestinal organ systems, e.g., the pan-creatic exocrine or endocrine cells and gastric parietal cells, the synergistic action between cAMP-and calcium-mediated responses has been established. A secretagogue which mobilizes cellular calcium (carbachol, cholecystokinin, bombesin, or the calcium ionophore A23187) potentiates the action of a secretagogue that acts through, or mimics the action of cAMP (vasoactive intestinal polypeptide [VIP],' secretin, or 8-Br-AMP) on amylase secretion from dispersed pancreatic acini of rat and guinea pig (1,2). Dibutyryl cAMP in combination with carbachol or A23187 amplifies enzyme secretion from rat pancreas (3,4).…”

Section: Introductionmentioning

confidence: 99%

Synergistic action of cyclic adenosine monophosphate- and calcium-mediated chloride secretion in a colonic epithelial cell line.

Cartwright¹,

McRoberts²,

Mandel³

et al. 1985

J. Clin. Invest.

167

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Vasoactive intestinal polypeptide (VIP) and the calcium ionophore A23187 caused dose-dependent changes in the potential difference and the short circuit current (I.) across confluent T84 cell monolayers mounted in modified Ussing chambers. Both VIP and A23187 stimulated net chloride secretion without altering sodium transport. Net chloride secretion accounted for the increase in I,<. When A23187 was tested in combination with VIP, net chloride secretion was significantly greater than predicted from the calculated sum of their individual responses indicating a synergistic effect. VIP increased cellular cyclic AMP (cAMP) production in a dose-dependent manner, whereas A23187 had no effect on cellular cAMP. We then determined whether VIP and A23187 activated different transport pathways. Earlier studies suggest that VIP activates a basolaterally localized, barium-sensitive potassium channel as well as an apically localized chloride conductance pathway. In this study, stimulation of basolateral membrane potassium efflux by A23187 was documented by preloading the monolayers with MRb+. Stimulation of potassium efflux by A23187 was additive to the VIP-stimulated potassium efflux. By itself, 0.3 ,uM A23187 did not alter transepithelial chloride permeability, and its stimulation of basolateral membrane potassium efflux caused only a relatively small amount of chloride secretion. However, in the presence of an increased transepithelial chloride permeability induced by VIP, the effectiveness of A23187 on chloride secretion was greatly augmented.Our studies suggest that cAMP and calcium each activate basolateral potassium channels, but cAMP also activates an apically localized chloride channel. Synergism results from cooperative interaction of potassium channels and the chloride channel.

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Effect of A23187 on amylase release from dispersed acini prepared from guinea pig pancreas

Cited by 6 publications

References 0 publications

Regulation of protein phosphorylation in pancreatic acini. Distinct effects of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate

Regulation of protein phosphorylation in pancreatic acini. Distinct effects of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate

Stimulus-secretion coupling in the developing exocrine pancreas: secretory responsiveness to cholecystokinin.

Synergistic action of cyclic adenosine monophosphate- and calcium-mediated chloride secretion in a colonic epithelial cell line.

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