Evidence against cyclic GMP as a mediator of the actions of secretagogues on amylase release from guinea-pig pancreas

Gardner, Jerry D.; Rottman, Alvin J.

doi:10.1016/0304-4165(80)90452-3

Cited by 33 publications

(10 citation statements)

References 24 publications

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“…In rat pancreatic acinar cells, phosphodiesterase inhibitors, which increase cGMP levels and elevate cGMP content induced by carbachol, do not alter amylase secretion under control conditions and during stimulation by carbachol [13]. These observations [4,11,13] suggest that cGMP does not play a major role in the stimulus-secretion coupling of pancreatic acinar cells.…”

Section: Introductionmentioning

confidence: 72%

“…Several reports have suggested that the guanylate cyclase/cGMP system is present in pancreatic acini but does not mediate stimulus-secretion coupling [4,11,13]. To address this question, cellular cGMP levels were measured using a [ 3 H]cGMP radioimmunoassay kit.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, Gunther and Jamieson have observed that, in guinea pig pancreatic acini, sodium nitroprusside (SNP) elevates levels of cGMP 60-fold over basal, but it does not trigger amylase secretion [11]. Similarly, Gardner and Rottman [4] have demonstrated that, in guinea pig pancreatic acini, several Ca 2+ -mobilizing secretagogues increase Ca 2+ efflux, cGMP (18-fold increase) and amylase secretion, whereas SNP and hydroxylamine, which increase cGMP 45-to 72-fold over basal, respectively, fail to increase Ca 2+ efflux or amylase secretion [4]. In rat pancreatic acinar cells, phosphodiesterase inhibitors, which increase cGMP levels and elevate cGMP content induced by carbachol, do not alter amylase secretion under control conditions and during stimulation by carbachol [13].…”

Section: Introductionmentioning

confidence: 88%

“…In pancreatic acinar cells, interactions between NO, cGMP and pancreatic enzyme secretion have been recognized previously, but direct roles for NO and cGMP in mediating the secretory process are controversial [4,[11][12][13]. Haymovits and Scheele [12] have reported that, in guinea pig pancreatic acini, several secretagogues, such as carbamylcholine chloride (carbachol) and cholecystokinin (CCK), which are Ca 2+ -mobilizing agents [38], increase cellular cGMP levels and high concentrations of cGMP analogs cause amylase secretion at a level approximately 30% of that observed with a maximal concentration of carbachol.…”

Section: Introductionmentioning

confidence: 99%

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Effect of uncoupling NO/cGMP pathways on carbachol- and CCK-stimulated Ca 2+ entry and amylase secretion from the rat pancreas

Yoshida

Tsunoda

Owyang

1997

Pfl�gers Archiv European Journal of Physiology

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Nitric oxide (NO) production reportedly regulates guanosine 3', 5'-cyclic monophosphate (cGMP) formation and Ca2+ influx in pancreatic acini. We have investigated the functional roles of the NO/cGMP messenger system in rat pancreatic acini. In dispersed acini, the levels of amylase secretion, cytosolic [Ca2+]([Ca2+]i), NO synthase, and cGMP were measured. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 0.01-100 microM) had no effect on amylase secretion induced by various concentrations of carbachol, cholecystokinin octapeptide (CCK-8) or the high affinity CCK agonist, JMV-180. Similarly, L-NAME up to 100 microM did not affect the changes in Ca2+ spiking evoked by these secretagogues; nor was Ca2+ entry, refilling or oscillation altered by L-NAME. Sub- and supramaximal concentrations of these secretagogues did not change NO synthase activities compared with basal levels. While sodium nitroprusside (SNP), a NO donor, caused a 9.4-fold increase in cGMP levels compared with basal levels, carbachol, CCK-8 and JMV-180 had no effect. In addition, the guanylate cyclase inhibitor LY 83583 (10 nM to 10 microM) altered neither amylase secretion nor Ca2+ signaling induced by these secretagogues. These findings indicate that the stimulatory action of carbachol or CCK-8 is not mediated by NO or cGMP. To investigate whether cGMP stimulates pancreatic secretion we showed that both SNP and a cell-permeant cGMP analog at 0.1-1 mM stimulated amylase secretion and Ca2+ transients to a level equal to 10-15% and 13-24%, respectively, of those observed with maximal concentrations of secretagogues. The guanylate cyclase activator guanylin (1-10 microM), which increased cGMP levels 2.4-fold compared with basal levels, elicited a small amount of amylase secretion and a small Ca2+ transient. In conclusion, exogenous NO is capable of increasing endogenous cGMP, which results in a modest increase in the [Ca2+]i transient and pancreatic amylase secretion. However, the NO/cGMP system does not appear to be involved significantly in the mediation of Ca2+ signaling and amylase secretion stimulated by carbachol and CCK-8.

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Section: Introductionmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Effect of uncoupling NO/cGMP pathways on carbachol- and CCK-stimulated Ca 2+ entry and amylase secretion from the rat pancreas

Yoshida

Tsunoda

Owyang

1997

Pfl�gers Archiv European Journal of Physiology

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“…NOS activity in isolated cell/acini in response to secretagogues was detected using arginine to citrulline conversion (Gukovskaya & Pandol 1994;Wrenn et al 1994;Ahn et al 1998), by evaluating nitrite concentration (Wrenn et al 1994;Ahn et al 1998;Jaworek et al 2000), or cGMP production (Haymovits & Scheele 1976;Gardner & Rottman 1980;Pandol & Schoeffield-Payne 1990;Wrenn et al 1994;Gilon et al 1995;Gukovskaya & Pandol 1995;Xu et al 1997;Yoshida et al 1997;Ahn et al 1998). Leptin receptor (Jaworek et al 2002a) and protease-activated receptor-2 stimulation (Kawabata et al 2002) was also able to generate NO in acinar cells.…”

Section: Localization Of Nitric Oxide Synthase In Pancreasmentioning

confidence: 99%

Free radicals and the pancreatic acinar cells: role in physiology and pathology

Chvanov

Petersen

Tepikin

2005

Phil. Trans. R. Soc. B

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Reactive oxygen and nitrogen species (ROS and RNS) play an important role in signal transduction and cell injury processes. Nitric oxide synthase (NOS)-the key enzyme producing nitric oxide (NO)-is found in neuronal structures, vascular endothelium and, possibly, in acinar and ductal epithelial cells in the pancreas. NO is known to regulate cell homeostasis, and its effects on the acinar cells are reviewed here. ROS are implicated in the early events within the acinar cells, leading to the development of acute pancreatitis. The available data on ROS/RNS involvement in the apoptotic and necrotic death of pancreatic acinar cells will be discussed.

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