title: Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion.
abstract: It is generally assumed that the functional consequences of stimulation with Ca2+ -mobilizing agonists are derived exclusively from the second messenger action of intracellular Ca2+, acting on targets inside the cells. However, during Ca2+ signaling events, Ca2+ moves in and out of the cell, causing changes not only in intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous cell types possess an extracellular Ca2+ "sensor" raises the question of whether these dynamic changes in external [Ca2+] may serve some sort of messenger function. We found that in intact gastric mucosa, the changes in extracellular [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were sufficient and necessary to elicit alkaline secretion and pepsinogen secretion, independent of intracellular [Ca2+] changes. These findings suggest that extracellular Ca2+ can act as a "third messenger" via Ca2+ sensor(s) to regulate specific subsets of tissue function previously assumed to be under the direct control of intracellular Ca2+.
authors.affiliation: Dipartimento di Fisiologia Generale ed Ambientale, Università di Bari, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Caroppo
authors.forename: Andrea
authors.initials: A
authors.lastname: Gerbino
authors.forename: Gregorio
authors.initials: G
authors.lastname: Fistetto
authors.forename: Matilde
authors.initials: M
authors.lastname: Colella
authors.forename: Lucantonio
authors.initials: L
authors.lastname: Debellis
authors.forename: Aldebaran M
authors.initials: AM
authors.lastname: Hofer
authors.forename: Silvana
authors.initials: S
authors.lastname: Curci
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D004566:Electrodes; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D008856:Microscopy, Fluorescence; D020116:Pepsinogen A / Q000737:chemistry / Q000378:metabolism; D011898:Ranidae; D015398:Signal Transduction; D013096:Spermine / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D013096:Spermine; D002217:Carbachol; D020116:Pepsinogen A; D000225:Adenine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium