Potency of various peptides as histamine liberators in the rat hind limb

The potency of several peptides and drugs as histamine liberators was assessed using the rat isolated hind limb preparation. Neurotensin (NT) and compound 48/80 (C48/80) were effective in concentrations as low as 10(-9) M and 10(-8) M, respectively. Threshold concentrations of vasoactive intestinal peptide (VIP) and substance P (SP) varied between 5 X 10(-7) to 5 X 10(-6) M while somatostatin (SS) was barely active at 6 X 10(-6) M. No histamine release could be detected following the use of high concentrations of thyrotropin releasing hormone (TRH) (6 X 10(-6) M), dynorphin (DYN) (6 X 10(-6) M) bradykinin (BK), des-Arg9-BK or bombesin (BB) (at 10(-5) M). Poly-L-Lysine and the calcium ionophore A23187 were about 100 times less active than NT. Concanavalin A (Con A) was inactive at 10(-6) M. These results indicate that NT is more potent (on a molar basis) as histamine liberator in the rat hind limb preparation (which contains a large population of cutaneous and subcutaneous mast cells) than any of the other compounds tested. Histamine release by NT was inhibited by preexposure of the rat hind limb mast cells to a high concentration of SP (1.5 X 10(-6) M). This result adds further support to the hypothesis suggesting that NT and SP might share a common mechanism of action and/or act through common receptors at least in rat mast cells.