Neurotensin stimulates exocytotic histamine secretion from rat mast cells and elevates plasma histamine levels.

Abstract

Neurotensin stimulated histamine release and granule extrusion when applied to isolated rat peritoneal mast cells. This secretory response was prevented by the removal of Ca or energy and was not accompanied by the release of lactic dehydrogenase. The secretory response produced by neurotensin was prevented by prior treatment of mast cells with cromoglycate. The i.v. injection of neurotensin into anesthetized rats produced a rapid and significant increase in the level of blood histamine that was dependent upon the dose of neurotensin. Treatment of rats with compound 48/80, 24 h before neurotensin, abolished the elevation in blood histamine caused by neurotensin. The i.v. injection of cromoglycate 1-2 min before neurotensin greatly reduced the response to neurotensin. The intradermal injection of neurotensin (0.03-30 pmol) increased capillary permeability in rats pre-treated i.v. with Evans Blue. This response was abolished by the antihistamine, diphenhydramine. Increasing the dose of neurotensin to 300 pmol partially overcame this inhibition by diphenhydramine. Results demonstrate that neurotensin can elicit an exocytotic secretory response from isolated rat peritoneal mast cells and elevate histamine levels in blood. Some physiological effects of neurotensin may be due to stimulation of mast cell secretion.