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 inhibited basal and gastrin-stimulated histamine synthesis through a dual mechanism involving a decrease in the affinity of histidine decarboxylase (HDC) for its substrate (L-histidine) and a reduction in the number of functional HDC molecules. H-89 (an inhibitor of cAMP-dependent protein 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 effect of H-89 and to prevent the somatostatin-induced reduction in HDC affinity for L-histidine. Thus, the somatostatin-induced reduction in affinity seems to involve a PTX-sensitive G protein and an inhibition of the cAMP-dependent pathway. On the other hand, the somatostatin-induced decrease in the number of functional HDC molecules seems to be PTX insensitive and independent from a modulation of the cAMP pathway, and does not seem to involve a significant change in HDC messenger RNA expression or a regulation of protein kinase C. The exact nature of this second mechanism will need further studies to be elucidated.
Hollande
F
F
Laboratoire de Biochimie des Membranes, Faculté de Pharmacie, Montpellier, France.
Choquet
A
A
Bali
J P
JP
Magous
R
R
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013004:Somatostatin / Q000494:pharmacology*; D013270:Stomach / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D005755:Gastrins; D006633:Histamine Antagonists; D008762:Methylhistidines; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; C028309:alpha-fluoromethylhistidine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D006640:Histidine Decarboxylase