L-TYPE CALCIUM CHANNELS REGULATE GASTRIN-RELEASE FROM HUMAN ANTRAL G-CELLS

In mRNA samples isolated from a gastrin (G) cell-enriched human antral cell preparation, reverse transcription-polymerase chain reaction ide ntified products encoding part of the alpha(1)-subunit of class C and D L-type voltage-dependent Ca2+ channels (VDCCs). Analysis of the poly merase chain reaction products demonstrated a 100% homology with the k nown 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)-ag onist) and forskolin was abolished by blockade of L-type VDCCs; the ef fect of 3.6 mM extracellular Ca2+ was only partially reversed. In G ce lls the rise in intracellular Ca2+ observed in response to increasing extracellular Ca2+ from 0.5 to 3.6 mM was reduced by nitrendipine. The se results indicated that human antral cells expressed class C and D L -type VDCCs. Activation of CT cells with beta-adrenergic agonists requ ired an influx of extracellular Ca2+ through these channels to stimula te gastrin release. However, activation of L-type channels was not the only mechanism underlying Ca2+-stimulated gastrin release.