NEUROPEPTIDE-Y AND TRUNCATED NEUROPEPTIDE-Y ANALOGS EVOKE HISTAMINE-RELEASE FROM RAT PERITONEAL MAST-CELLS - A DIRECT EFFECT ON G-PROTEINS

Several regulatory peptides, including neuropeptide Y, can release his tamine from mast cells. In the present study we investigated which par ts of the neuropeptide Y molecule are required to evoke the release of histamine from isolated rat peritoneal mast cells. In addition, we ex amined whether the histamine release evoked by neuropeptide Y (and by compound 48/80) is sensitive to the G protein inhibitors pertussis tox in and benzalkonium chloride. Neuropeptide Y released histamine in a c oncentration-dependent manner. Also a neuropeptide Y analog with the c enter past substituted by 8-aminooctanoic acid, [Aoc(2-27)]neuropeptid e Y, and the cyclic form of the C-terminal hexapeptide, cyclic neurope ptide Y-(31-36), released histamine. The three peptides were equally e ffective and equally potent. Neuropeptide Y-(1-24)NH2 also released hi stamine, but its efficacy was low. The rank order of potency of the an alogs tested did not agree with that of any of the previously known or postulated neuropeptide Y receptors. Pretreatment of mast cells with pertussis toxin or benzalkonium chloride markedly inhibited the histam ine release evoked by neuropeptide Y, [Aoc(2-27)]neuropeptide Y and co mpound 48/80. In conclusion, most of the histamine-releasing activity of neuropeptide Y resides in the six C-terminal amino acid residues. T he release appears to be G protein-dependent and is probably not recep tor mediated.