Neuropeptide γ‐(l‐9)‐Peptide: A Major Product of the Posttranslational Processing of γ‐Preprotachykinin in Rat Tissues

Abstract

gamma-Preprotachykinin mRNA is the most abundant tachykinin mRNA in rat tissues, but the pathway of post-translational processing of its translation product is unknown. An antiserum was raised against the synthetic peptide Asp-Ala-Gly-His-Gly-Gln-Ile-Ser-His [neuropeptide gamma-(1-9)-peptide, equivalent to gamma-preprotachykinin-(72-80)-peptide], that showed < 1% reactivity with intact neuropeptide gamma and other tachykinins. Neuropeptide gamma-(1-9)-peptide was detected by radioimmunoassay 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 concentrations 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 retention time as synthetic neuropeptide gamma-(1-9)-peptide. The synthetic peptide did not contract or relax isolated rat trachea, superior mesenteric artery, stomach fundus, or ileum, and the peptide did not affect the ability of neuropeptide gamma to contract the rat fundus. It is concluded that, in rat tissues, Lys70-Arg71 in gamma-preprotachykinin is a major site of posttranslational processing, but the resulting product, neuropeptide gamma-(1-9)-peptide, is neither an agonist nor an antagonist at the neurokinin-2 (NK-2) receptor.