title: Intracellular signal transduction during gastrin-induced histamine secretion in rat gastric ECL cells.
abstract: Activation of G(q) protein-coupled receptors usually causes a biphasic increase in intracellular calcium concentration ([Ca(2+)](i)) that is crucial for secretion in nonexcitable cells. In gastric enterochromaffin-like (ECL) cells, stimulation with gastrin leads to a prompt biphasic calcium response followed by histamine secretion. This study investigates the underlying signaling events in this neuroendocrine cell type. In ECL cells, RT-PCR suggested the presence of inositol 1,4,5-trisphosphate receptor (IP(3)R) subtypes 1-3. The IP(3)R antagonist 2-aminoethoxydiphenyl borate abolished both gastrin-induced elevation of [Ca(2+)](i) and histamine release. Thapsigargin increased [Ca(2+)](i), however, without inducing histamine secretion. In thapsigargin-pretreated cells, gastrin increased [Ca(2+)](i) through calcium influx across the plasma membrane. Both nimodipine and SKF-96365 inhibited gastrin-induced histamine release. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate induced histamine secretion, an effect that was prevented by nimodipine. In summary, gastrin-stimulated histamine release depends on IP(3)R activation and plasmalemmal calcium entry. Gastrin-induced calcium influx was mediated by dihydropyridine-sensitive calcium channels that appear to be L-type channels activated through a pathway involving activation of PKC.
authors.affiliation: II. Medizinische Klinik und Poliklinik, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Zanner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hapfelmeier
authors.forename: Manfred
authors.initials: M
authors.lastname: Gratzl
authors.forename: Christian
authors.initials: C
authors.lastname: Prinz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004759:Enterochromaffin Cells / Q000502:physiology*; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D005755:Gastrins / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007425:Intracellular Membranes / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000166:cytology / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005456:Fluorescent Dyes; D005755:Gastrins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2