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

Abstract: γ-Preprotachykinin mRNA is the most abundant tachykinin mRNA in rat tissues, but the pathway of posttranslational processing of its translation product is unknown. An antiserum was raised against the synthetic peptide Asp-Ala-Gly-His-Gly-Gln-lle-Ser-His neuropeptide γ-(1-9)-peptide, equivalent to γ-preprotachykinin-(72-80)-peptide], that showed <1% reactivity with intact neuropeptide γ and other tachykinins. Neuropeptide γ-(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 γ-(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 γ-(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 7 to contract the rat fundus. It is concluded that, in rat tissues, Lys⁷⁰-Arg⁷¹ in 7-preprotachykinin is a major site of posttranslational processing, but the resulting product, neuropeptide γ-(1-9)-peptide, is neither an agonist nor an antagonist at the neurokinin-2 (NK-2) receptor.