Stimulation of histamine release by the peptide kinetensin.

The peptide kinetensin isolated from pepsin-treated human plasma induced a dose-dependent release of histamine when exposed to rat peritoneal mast cells. The threshold concentration was around 10(-6) M, the ED50 was 10(-5) M, and the optimal concentration of between 10(-4) to 10(-3) M released 80% of the total histamine. Kinetensin was 10 to 100 times less potent than neurotensin and equipotent with the opioid peptide dynorphin. The histamine release was clearly temperature-dependent, with no release occurring at 0 degrees or 45 degrees C and with an optimum around 37 degrees C. The histamine release was significantly reduced in the absence of extracellular calcium. Kinetensin also induced a dose-dependent increase in vascular permeability when injected intradermally into rats. The findings indicate that kinetensin is a potent histamine releaser in the rat and may serve as an inflammatory mediator.