SHORT-TERM INHIBITORY EFFECT OF SOMATOSTATIN ON GASTRIC HISTAMINE SYNTHESIS

In this study we investigated the short term effect of somatostatin on histamine synthesis in a cell population isolated from rabbit gastric mucosa and enriched in enterochromaffin-like cells. Somatostatin inhi bited basal and gastrin-stimulated histamine synthesis through a dual mechanism involving a decrease in the affinity of histidine decarboxyl ase (HDC) for its substrate (L-histidine) and a reduction in the numbe r of functional HDC molecules. H-89 (an inhibitor of cAMP-dependent pr otein kinase) mimicked somatostatin-induced reduction of HDC affinity, which, on the contrary, was selectively reversed by pertussis toxin ( PTX). Furthermore, forskolin was shown to reverse the inhibitory effec t of H-89 and to prevent the somatostatin-induced reduction in HDC aff inity for L-histidine. Thus, the somatostatin-induced reduction in aff inity seems to involve a PTX-sensitive G protein and an inhibition of the cAMP-dependent pathway. On the other hand, the somatostatin-induce d decrease in the number of functional HDC molecules seems to be PTX i nsensitive and independent from a modulation of the cAMP pathway, and does not seem to involve a significant change in HDC messenger RNA exp ression or a regulation of protein kinase C. The exact nature of this second mechanism will need further studies to be elucidated.