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Carbachol inhibits stimulant-induced increases in fundic D-cell cytosolic Ca2+ concentration
1Third Department of Internal Medicine, Kobe University School of Medicine, Japan.
Abstract:
We undertook these studies to examine the mechanisms by which carbachol inhibits somatostatin release. For these studies, we utilized cultured D-cells isolated from the canine gastric fundus. Carbachol inhibited somatostatin release induced by both pentagastrin and 12-O-tetradecanoyl-phorbol-13-acetate but did not alter the redistribution of protein kinase C induced by these agents. In contrast, carbachol diminished the increase in D-cell cytosolic free calcium levels ([Ca2+]i) induced by pentagastrin, and this effect was no longer evident after pretreatment of D-cells with pertussis toxin. Although carbachol by itself had no effect on [Ca2+]i, after pretreatment of D-cells with pertussis toxin, carbachol both enhanced [Ca2+]i and stimulated somatostatin release. These data indicate that carbachol activates signals in D-cells that result in both increase and decrease in [Ca2+]i. The latter effect, which appears to be mediated via a pertussis toxin-sensitive guanine nucleotide binding protein, may be one mechanism responsible for cholinergic inhibition of somatostatin release.
Insights
Carbachol inhibits canine gastric somatostatin release by modulating calcium levels via a pertussis toxin-sensitive pathway. This cholinergic signaling affects intracellular calcium, impacting somatostatin secretion from D-cells.
Area of Science:
- Gastroenterology
- Cell Signaling
- Endocrinology
Background:
- Somatostatin is a key regulator of gastric function.
- Cholinergic pathways, like carbachol, influence hormone release.
- Understanding the precise mechanisms of somatostatin regulation is crucial.
Purpose of the Study:
- To investigate the cellular mechanisms by which carbachol inhibits somatostatin release from canine gastric D-cells.
- To elucidate the role of intracellular calcium and protein kinase C in this inhibitory process.
Main Methods:
- Utilized cultured D-cells isolated from the canine gastric fundus.
- Assessed somatostatin release induced by pentagastrin and 12-O-tetradecanoyl-phorbol-13-acetate.
- Measured changes in cytosolic free calcium levels ([Ca2+]i) and protein kinase C redistribution.
- Employed pertussis toxin pretreatment to investigate G-protein involvement.
Main Results:
- Carbachol inhibited pentagastrin- and 12-O-tetradecanoyl-phorbol-13-acetate-induced somatostatin release.
- Carbachol did not affect protein kinase C redistribution.
- Carbachol diminished pentagastrin-induced increases in [Ca2+]i, an effect blocked by pertussis toxin.
- Pertussis toxin pretreatment enabled carbachol to increase [Ca2+]i and stimulate somatostatin release.
Conclusions:
- Carbachol elicits opposing effects on D-cell cytosolic calcium, involving both increases and decreases.
- The inhibitory effect of carbachol on somatostatin release is mediated by a pertussis toxin-sensitive pathway, likely involving a guanine nucleotide-binding protein.
- This pertussis toxin-sensitive pathway modulating calcium is a key mechanism for cholinergic inhibition of somatostatin release.