Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion.
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+.
Caroppo
Rosa
R
Dipartimento di Fisiologia Generale ed Ambientale, Università di Bari, Italy.
Gerbino
Andrea
A
Fistetto
Gregorio
G
Colella
Matilde
M
Debellis
Lucantonio
L
Hofer
Aldebaran M
AM
Curci
Silvana
S
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
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