Induction of Enzyme Secretion in Rat Pancreatic Slices Using the Ionophore A-23187 and Calcium

Eimerl, Sarah; Savion, Naphtali; Heichal, Ora; Selinger, Zvi

doi:10.1016/s0021-9258(19)42572-6

Cited by 96 publications

(4 citation statements)

References 19 publications

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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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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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“…The increase in pancreatic enzyme secretion caused by CCK or cholinergic agents is reduced or abolished when calcium is removed from the incubation medium [23][24][25]. Furthermore, divalent cation ionophores such as A23187 can increase pancreatic enzyme secretion, and this increase, like that caused by CCK or cholinergic agents, can be abolished by removing extracellular calcium [12,26,27]. These observations were initially interpreted to indicate that secretagogues such as CCK or cholinergic agents cause stimulation of pancreatic enzyme secretion by virtue of their ability to increase the inward movement of calcium from the extracellular medium into pancreatic acinar cells [26].…”

Section: Calciummentioning

confidence: 99%

“…Furthermore, divalent cation ionophores such as A23187 can increase pancreatic enzyme secretion, and this increase, like that caused by CCK or cholinergic agents, can be abolished by removing extracellular calcium [12,26,27]. These observations were initially interpreted to indicate that secretagogues such as CCK or cholinergic agents cause stimulation of pancreatic enzyme secretion by virtue of their ability to increase the inward movement of calcium from the extracellular medium into pancreatic acinar cells [26]. Subsequently, direct measurements of the effect of secretagogues on transport of 45Ca by pancreatic acinar cells showed that CCK and cholinergic agents do not alter the inward movement of calcium into the tissue but cause a significant increase in calcium outflux [9-14, 24, 25].…”

Section: Calciummentioning

confidence: 99%

Biochemical basis of action of gastrointestinal hormones

Gardner

1979

World j. surg.

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The actions of secretin and VIP on pancreatic enzyme secretion result from their abilities to activate adenylate cyclase and increase cellular cyclic AMP. The actions of cholecystokinin, cholinergic agents, caerulein, bombesin, litorin, physalaemin, and eledoisin on pancreatic enzyme secretion result from their abilities to cause release of bound cellular calcium. Although this action causes an increase in cellular cyclic GMP, it remains to be determined whether or not cyclic GMP is a mediator of the action of secretagogues on pancreatic enzyme secretion. Secretagogues that increase cyclic AMP do not alter calcium transport or cyclic GMP and do not modify the changes in calcium transport or cyclic GMP caused by other agents. Secretagogues that cause release of cellular calcium and increase cyclic GMP do not alter cyclic AMP and do not cause major changes in the increase in cyclic AMP produced by other secretagogues. Although the two mechanisms of action of pancreatic secretagogues are initially distinct, they interact at some presently undefined step, and this interaction results in potentiation of enzyme secretion. The finding that two agents potentiate each other has important implications for the mechanisms of action of the two agents and has potential therapeutic applications.

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“…CB prevents phagocytosis but facilitates the secretory release of lysosomal enzymes from granulocytes (10,13). The calcium ionophore A-23187 binds to cell membranes and chelates calcium, thereby promoting calcium influx (16) which may account for its capacity to induce secretion of hormones (insulin) (17), enzymes (amylase) (18), and mediators (histamine, ECF-A) (19,20). Lysosomal enzymes apparently are released minimally by ionophore (5).…”

mentioning

confidence: 99%

Histaminase release from human granulocytes.

Zeiger¹,

Twarog²,

Colten³

1976

The Journal of Experimental Medicine

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Histaminase (EC-1.4.3.6), one of the two catabolic enzymes for histamine, is contained in human granulocytes. Opsonized zymosan or the calcium ionophore A-23187 induce a dose-dependent release of histaminase from human granulocytes in vitro. Release is completed within 30 min, is temperature dependent, and requires divalent cations. Opsonized zymosan-induced histaminase release was maximal in the presence of both calcium and magnesium, whereas ionophore release was magnesium independent. The total cellular content of histaminase could be released by both opsonized zymosan and ionophore. In contrast, only 25% of the cellular beta glucuronidase, a lysosomal enzyme, was released after maximal stimulation with opsonized zymosan; there was minimal release of beta glucuronidase with ionophore. Zymosan- and ionophore-induced histaminase release was inhibited by agents that are presumed to interfere with cell metabolism and disrupt microtubules. Human granulocytes therefore may modulate the effect of histamine by releasing histaminase at a site of inflammation. Studies of granulocyte histaminase release in vitro may also provide a new model to explore granulocyte function and secretion.

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Induction of Enzyme Secretion in Rat Pancreatic Slices Using the Ionophore A-23187 and Calcium

Cited by 96 publications

References 19 publications

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

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

Biochemical basis of action of gastrointestinal hormones

Histaminase release from human granulocytes.

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