L-type calcium channels regulate gastrin release from human antral G cells

Abstract

In mRNA samples isolated from a gastrin (G) cell-enriched human antral cell preparation, reverse transcription-polymerase chain reaction identified products encoding part of the alpha 1-subunit of class C and D L-type voltage-dependent Ca2+ channels (VDCCs). Analysis of the polymerase chain reaction products demonstrated a 100% homology with the known human gene sequences. An antibody to the class D alpha 1-subunit immunostained 30-40% of the cultured cells; of these 90% were gastrin immunoreactive. Gastrin release stimulated by terbutaline (beta 2-agonist) and forskolin was abolished by blockade of L-type VDCCs; the effect of 3.6 mM extracellular Ca2+ was only partially reversed. In G cells the rise in intracellular Ca2+ observed in response to increasing extracellular Ca2+ from 0.5 to 3.6 mM was reduced by nitrendipine. These results indicated that human antral cells expressed class C and D L-type VDCCs. Activation of G cells with beta-adrenergic agonists required an influx of extracellular Ca2+ through these channels to stimulate gastrin release. However, activation of L-type channels was not the only mechanism underlying Ca(2+)-stimulated gastrin release.

In Vivo Epithelial Wound Repair Requires Mobilization of Endogenous Intracellular and Extracellular Calcium

“…Control in vitro experiments (supplemental Fig. S2D) (33), and G cells (10). A voltage-activated calcium channel blocker, verapamil, significantly inhibited the speed of gastric repair (Fig.…”

“…Thus, luminal Ca 2ϩ contributes to the regulatory control of normal physiologic functions in the amphibian stomach. In mammalian systems, reports have only defined the presence of agoniststimulated intracellular Ca 2ϩ mobilization in isolated gastric glands or isolated surface cells (7,9,10).…”

Antral G-cell in gastrin and gastrin-cholecystokinin knockout animals

“…Because gastrin had been knocked out without the insertion of a reporter gene, the G-cells had to be identified by using other markers. The following genes are expressed by G-cells and can serve as G-cell markers: chromogranin B (CgB; Cetin et al 1992), the a 1d -subunit of the voltagegated Ca 2+ channel (Ray et al 1997) and PC1/3 (Scopsi et al 1995). The CgB antiserum only stained a minor fraction of the G-cells and, instead, mainly stained the Dcells (data not shown).…”

“…The CgB antiserum only stained a minor fraction of the G-cells and, instead, mainly stained the Dcells (data not shown). The a 1d -subunit of the voltage-gated Ca 2+ channel has also been demonstrated on G-cells (Ray et al 1997); only a subset of G-cells in the wildtype mouse antrum stained with antiserum to this subunit. Furthermore, in both KO strains, immunoreactivity for the a 1d -subunit of the voltage-gated Ca 2+ channel antiserum was lost (data not shown).…”

Gastric Functions in Gastrin Gene Knock‐Out Mice

“…1): 1) Luminal nutrients (i.e. amino acids, especially aromatic), dietary amines and Ca 2+ , stimulate secretion of gastrin from G‐cells presumably by acting directly on receptors located on the luminal side of the G‐cells (Hersey & Sachs 1995; Ray et al 1997a & b; Conigrave et al 2000). 2) Gastric nerves, which in response to local and central signals release gastrin‐releasing peptide and acetylcholin, both subsequently induce gastrin secretion from the G‐cells through interaction with their respective receptors.…”