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.