Somatostatin-induced histamine secretion in mast cells. Characterization of the effect.
Somatostatin, in concentrations up to 100 ng/ml, had no effect on mast cell secretion induced either by compound 48/80 or by the ionophore A23187. In higher concentration somatostatin induced mast cell secretion. Light and electron microscopic observations showed that the secretory response was identical with that induced by 48/80 and involved extrusion of secretory granules by exocytosis. As with 48/80, this response to somatostatin was inhibited by treating the mast cells with EDTA or EGTA or by exposing them briefly to A23187 in calcium-free media, all of which procedures seemingly deplete cellular calcium stores. Reintroduction of calcium (but not magnesium), restored secretory responsiveness. Somatostatin-induced secretion further resembled that induced by 48/80 or A23187 in its intensity, rapid time course, and dependence on albumin. Pretreatment of mast cells with dibutyryl cyclic AMP or 8-bromo cyclic AMP substantially reduced the secretory responses to both somatostatin and 48/80 but had little effect on the response to A23187. Somatostatin, like 48/80, lowered intracellular cyclic AMP levels in a time and dose-dependent fashion. Finally, as earlier found for 48/80, somatostatin attached to Sepharose columns retarded the passage of mast cells and elicited histamine release indicating an action at the cell surface. The stimulant action of somatostatin is thus very similar to that of the classic mast-cell secretagogue compound 48/80.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D013004:Somatostatin; D000242:Cyclic AMP; D002118:Calcium