Secretory and biosynthetic responses of gastrin and somatostatin to acute changes in gastric acidity.
The activity of gastric parietal cells in terms of hydrochloric acid (HCl) secretion is regulated by the interaction of stimulatory substances (e.g. gastrin) and inhibitors (e.g. somatostatin) acting in an endocrine and paracrine mode, as well as luminal factors. In the present study the following parameters were measured: the synthesis (mRNA), storage (tissue peptide concentration) and secretion (plasma peptide concentration) of somatostatin and gastrin following short-term treatment of rats with pentagastrin (acid stimulant), secretin, omeprazole (reduces gastric acidity by inactivating gastric H/K ATPase) and the somatostatin analogue octreotide (reduces gastric acidity by inhibiting both the parietal cell and gastrin). The mRNA coding for H/K ATPase and carbonic anhydrase II (CA II), the two enzymes responsible for the generation of hydrogen ions from the parietal cell, were also quantitated. In response to octreotide, somatostatin peptide and mRNA levels in the fundus rose to 180 +/- 16% (P < 0.001) and 1073 +/- 356% (P < 0.05) of control, respectively. In contrast, octreotide caused a decrease in antral somatostatin peptide and its mRNA did not change significantly. No significant changes in synthesis, secretion or storage of gastrin were observed except for omeprazole induced hypergastrinaemia (580 +/- 76%, P < 0.001). H/K ATPase and CA II mRNA were largely unaffected except for an increase in CA II mRNA following octreotide and a decrease in H/K ATPase mRNA after pentagastrin. These data support the concept of the differential control of antral and fundic somatostatin synthesis and provide evidence for a regulatory loop by which somatostatin can influence its own synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Kapuscinski
M
M
University of Melbourne Department of Surgery, Austin Hospital, Heidelberg, Victoria, Australia.
Shulkes
A
A
D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D009853:Omeprazole / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
D004791:Enzyme Inhibitors; D005755:Gastrins; D012333:RNA, Messenger; D013004:Somatostatin; D000251:Adenosine Triphosphatases; D002256:Carbonic Anhydrases; D009853:Omeprazole