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Stimulus‐secretion coupling in rat pancreas: role of sodium, calcium and cyclic nucleotides studied by X‐537A and BrX‐537A.
Author(s) -
Singh M
Publication year - 1980
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1980.sp013226
Subject(s) - chemistry , ionophore , secretion , extracellular , medicine , amylase , calcium , egta , endocrinology , sodium , divalent , ouabain , veratridine , biophysics , biochemistry , biology , enzyme , organic chemistry , sodium channel
1. 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 secretory 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 45Ca2+. 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.