NEUROPEPTIDE GAMMA-(1-9)-PEPTIDE - A MAJOR PRODUCT OF THE POSTTRANSLATIONAL PROCESSING OF GAMMA-PREPROTACHYKININ IN RAT-TISSUES

Gamma-Preprotachykinin mRNA is the most abundant tachykinin mRNA in ra t tissues, but the pathway of posttranslational processing of its tran slation product is unknown. An antiserum was raised against the synthe tic peptide Asp-Ala-Gly-His-Gly-Gln-Ile-Ser-His [neuropeptide gamma-(1 -9)-peptide, equivalent to gamma-preprotachykinin-(72-80)-peptide], th at showed <1% reactivity with, intact neuropeptide gamma and other tac hykinins. Neuropeptide gamma-(1-9)-peptide was detected by radioimmuno assay in relatively high concentrations in extracts of regions of rat brain and gastrointestinal tract. These concentrations correlated with (r = 0.99), but were significantly (p < 0.05) less than, the concentr ations of neurokinin A-like immunoreactivity. The neuropeptide gamma-( 1-9)-like immunoreactivity in an extract of rat brain was eluted from a reverse-phase HPLC column in a single fraction with the same retenti on time as synthetic neuropeptide gamma-(1-9)-peptide. The synthetic p eptide did not contract or relax isolated rat trachea, superior mesent eric artery, stomach fundus, or ileum, and the peptide did not affect the ability of neuropeptide gamma to contract the rat fundus. It is co ncluded that, in rat tissues, Lys70-Arg71 in gamma-preprotachykinin is a major site of posttranslational processing, but the resulting produ ct, neuropeptide gamma-(1-9)-peptide, is neither an agonist nor an ant agonist at the neurokinin-2 (NK-2) receptor.