[Calcium-dependent signaling of acid secretion in isolated parietal cells from guinea pigs and its modification by ethanol].
Treatment of isolated parietal cells from guinea pig gastric mucosa with ethanol caused a rapid increase in [Ca2+]i and concomitant decrease in the capacity for carbachol-stimulated acid secretion in a dose dependent manner. Carbachol rapidly increased the [Ca2+]i from trimethoxybenzoic acid 8-(diethylamino)-octyl ester sensitive intracellular pool. In contrast, the increase with ethanol was through La3+ sensitive Ca2+ channel from external source, which suppressed the Ca2+ response subsequently stimulated with carbachol. Pretreatment of the cells with EGTA or La3+ completely prevented the elevation of [Ca2+]i with ethanol and preserved the Ca2+ response to carbachol. These findings indicate that ethanol-induced elevation of [Ca2+]i may desensitize the stimulation of carbachol. Furthermore, treatment of the parietal cells with ethanol increased the activity of protein kinase C in both cytosolic and membrane fractions of the cells. Activation of protein kinase C with phorbol diester suppressed the capacity for acid secretion. These results suggest that ethanol may inhibit the carbachol-stimulated acid secretion through the desensitization of Ca2+ response and the activation of protein kinase C.
Niki
S
S
Department of Preventive Medicine, Kyoto Prefectural University of Medicine.
Rokutan
K
K
Nakamura
K
K
Ogihara
S
S
Kutsumi
H
H
Saitoh
T
T
Aoike
A
A
Kawai
K
K
D000818:Animals; D002118:Calcium / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000431:Ethanol; D011493:Protein Kinase C; D002118:Calcium