Direct cytoplasmic CA(2+) responses to gastrin-releasing peptide in single beta cells.
The neuropeptide gastrin releasing peptide (GRP) stimulates insulin secretion and induces oscillations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](cyt)) in clonal insulinoma cells. It is not known whether GRP affects [Ca(2+)](cyt) in normal beta cells. We investigated, in single, normal, mouse islet beta cells, the effects of GRP on [Ca(2+)](cyt), by dual wavelength spectrophotofluorometry. Beta cells were identified by their typical response to glucose or tolbutamide. At 15 mM glucose, GRP (100 nM) evoked an immediate [Ca(2+)](cyt) transient to 423 +/- 48 nM compared to 126 +/- 18 nM before GRP (P < 0.001). After the initial transient, [Ca(2+)](cyt) exhibited either a sustained elevation or oscillations. At 3.3 mM glucose, in cells with a non-oscillating [Ca(2+)](cyt), GRP stimulated a prompt increase in [Ca(2+)](cyt) (from 60 +/- 6 to 285 +/- 30 nM, P = 0.024) followed by either a sustained increase in [Ca(2+)](cyt) or [Ca(2+)](cyt) oscillations. We conclude that GRP promptly elevates [Ca(2+)](cyt) by a direct action in normal mouse pancreatic beta cells.
Karlsson
S
S
Wallenberg Laboratory, Department of Medicine, Lund University, SE-205 02 Malmö, Sweden. Sven.Karlsson@medforsk.mas.lu.se
Sundler
F
F
Ahrén
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010191:Pancreatic Polypeptide / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism
D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D019886:Gastrin-Releasing Peptide; D005934:Glucagon; D005947:Glucose; D002118:Calcium