Inhibitory action of somatostatin on isolated gastric glands and parietal cells.
The action of somatostatin in vitro was characterized using glands and parietal cells isolated from rabbit gastric mucosa. In the presence of the reducing agent dithiothreitol, somatostatin was found to inhibit gastrin- and histamine-stimulated acid formation in glands as measured by [14C]aminopyrine (AP) accumulation and oxygen consumption, both measurements that appear to be reliable indexes of parietal cell acid formation. In glands the inhibition of the secretory response to gastrin was more potent (60-80%) than that to histamine (15-25%). The kinetics of somatostatin inhibition of responses to both agents were noncompetitive. The apparent IC50 for the partial somatostatin inhibition of histamine-stimulated AP accumulation was similar to that for gastrin (approx 3 X 10(-9) M) when maximum concentrations of histamine (10(-4) M) or gastrin (10(-7) M) were used. The inhibitory action of somatostatin appeared to be specific, inasmuch as this peptide had no significant effect on basal secretion or secretion stimulated by carbachol, dibutyryl cAMP, cholera toxin, or elevated extracellular K+. In purified parietal cell preparations, somatostatin inhibited histamine- but not gastrin-stimulated AP accumulation. Moreover, the inhibition of histamine-stimulated AP accumulation in parietal cells was more pronounced than in glands. These results suggest that somatostatin acts directly on parietal cells to inhibit histamine activation of H+ secretion. Somatostatin also acts indirectly to inhibit gastrin, perhaps by blocking the release of histamine from paracrine- or endocrinelike cells present in the glands.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D013004:Somatostatin / Q000494:pharmacology*
D005755:Gastrins; D000632:Aminopyrine; D013004:Somatostatin; D002927:Cimetidine; D006632:Histamine; D015056:1-Methyl-3-isobutylxanthine