Scyliorhinin I (Scy I) is a naturally occurring linear decapeptide tachykinin originally isolated from the intestine of the common dogfish, Scyliorhinus canicula. Its sequence is Ala-Lys-Phe-Asp-Lys-Phe-Tyr-Gly-Leu-Met-NH₂, and the conserved Phe-X-Gly-Leu-Met-NH₂ C-terminal motif places it within the tachykinin peptide family.

Unlike mammalian Substance P, which preferentially activates NK1, Scyliorhinin I shows high affinity at both NK1 and NK2 receptor systems while displaying much weaker NK3 activity. This dual profile makes it useful for comparative tachykinin pharmacology, receptor-subtype studies and investigation of sequence features that permit recognition by both NK1 and NK2 receptors.

Product Information

A Naturally Occurring Dual NK1/NK2 Tachykinin

Scyliorhinin I was originally purified from dogfish intestinal tissue on the basis of tachykinin-like smooth-muscle activity. Its sequence is chemically distinct from mammalian Substance P and Neurokinin A, although the peptides share the conserved amidated C-terminal motif characteristic of the tachykinin family.

This distinction is important when selecting experimental controls. Scyliorhinin I should not be treated simply as “shark Substance P.” It is an independent tachykinin with its own receptor-affinity profile.

Quantitative NK1 and NK2 Receptor Binding

Classical mammalian receptor-binding studies reported a K_i of approximately 0.9 nM at NK1 sites in rat submandibular gland membranes and approximately 2 nM at NK2 sites in hamster urinary bladder membranes.

In contrast, Scyliorhinin I showed substantially weaker agonist activity in NK3 receptor preparations. These data support its use as a dual NK1/NK2 tachykinin ligand rather than an NK3-selective peptide.

We recommend keeping these affinity values tied to their original species and tissue preparations. Potency measured with recombinant human TACR1 or TACR2 can differ because receptor expression, membrane environment and assay readout affect apparent ligand affinity.

Why Tyr7 Matters for Dual Receptor Activity

Position 7 is an important determinant of Scyliorhinin I receptor pharmacology. Structure–activity studies replacing Tyr7 with Val or Ile produced analogs with lower potency at NK1 and NK2 receptor systems.

Other aromatic substitutions at this position preserved NK1 activity more effectively than NK2 activity, indicating that residue 7 contributes differently to recognition by the two receptor subtypes.

This makes Scyliorhinin I particularly useful for studying how a single tachykinin sequence can maintain high affinity for both NK1 and NK2 rather than displaying the stronger subtype preference seen with many mammalian tachykinins.

Membrane-Induced Conformation

NMR and circular dichroism studies indicate that Scyliorhinin I is conformationally responsive to a membrane-like environment. In phospholipid micelles, residues in the central and C-terminal region can adopt helical conformations, including 3₁₀- and α-helical character.

We consider this relevant when interpreting receptor SAR because tachykinin recognition depends not only on linear sequence but also on the conformational ensemble presented near a membrane-associated GPCR.

Research Applications

Scyliorhinin I can support NK1 and NK2 receptor pharmacology, comparative tachykinin signaling, receptor-subtype differentiation, evolutionary neuropeptide studies and peptide structure–activity research.

It can also be compared with Substance P to examine the structural features associated with NK1-selective versus dual NK1/NK2 tachykinin activity.

Frequently Asked Questions

Is Scyliorhinin I the same as shark Substance P?

No. Scyliorhinin I is a distinct dogfish tachykinin. It shares the conserved tachykinin C-terminal motif with Substance P but has a different sequence and receptor profile.

Which receptors does Scyliorhinin I activate?

It shows high-affinity agonist activity at both NK1 and NK2 receptor systems and substantially weaker activity at NK3.

What receptor affinities have been reported?

Classical binding studies reported K_i values of approximately 0.9 nM at rat NK1 sites and 2 nM at hamster NK2 sites.

Why is Tyr7 important?

Substitution studies show that residue 7 strongly influences potency and the balance of NK1 versus NK2 receptor recognition.

Is the C-terminus amidated?

Yes. Scyliorhinin I terminates in Met-NH₂, consistent with the conserved amidated tachykinin pharmacophore.

Research Use Only.