Ranakinin: A Novel NK1 Tachykinin Receptor Agonist Isolated with Neurokinin B from the Brain of the Frog Rana ridibunda

An extract of the whole brain of the frog Rana ridibunda contained high concentrations of substance P‐like immunoreactivity, measured with an antiserum directed against the COOH‐terminal region of mammalian substance p and neurokinin b‐like immurtoreactivity, measured with an antiserum directed against the NH₂‐terminus of neurokinin B. The primary structure of the substance p‐related peptide (ranakinin) was established as: Lys‐Pro‐Asn‐Pro‐Glu‐Arg‐Phe‐Tyr‐Gly‐Leu‐Met‐NH₂. Mammalian substance P was not present in the extract. The primary structure of the neurokinin b‐related peptide was established as: Asp‐Met‐His‐Asp‐Phe‐Phe‐Val‐Gly‐Leu‐Met‐NH₂. This amino acid sequence is the same as that of mammalian neurokinin B. Ranakinin was equipotent with substance p and [Sar⁹,‐Met(O₂)¹¹]substance p in inhibiting the binding of ¹²⁵I‐Bolton‐Hunter‐[Sar⁹, Met(O₂)¹¹]substance p, a selective radio‐ligand for the NK1 receptor, to binding sites in rat subman‐dibular gland membranes (IC₅₀ 1.6 ± 0.3 nM; n = 5). It is concluded that ranakinin is a preferred agonist for the mammalian NK1 tachykinin receptor subtype.