Galanin (1-19): brain-quieting peptide fragment (human)

What this is

Galanin (1-19) is the front nineteen amino acids of human galanin, a small messenger molecule the body makes in nerves throughout the brain, spinal cord, and gut. Full-length human galanin is a 30-residue neuropeptide that quiets neuronal firing and is involved in pain, mood, seizure control, feeding, and hormone release (Kolakowski 1998). The N-terminal portion shown here (GWTLNSAGYLLGPHAVGNH) contains the part of the molecule that binds the galanin receptors; the rest of the natural peptide extends past residue 19 with sequence RSFS... and beyond (Freimann 2015). This card represents that N-terminal fragment as a research tool — not the full endogenous hormone and not a marketed drug.

History

Galanin was first isolated in the 1980s as a peptide ending in a C-terminal amide (the "-anin" suffix reflects that amide cap). Its receptors were then cloned one by one across the 1990s: the human galanin receptor GalR1 was cloned from a Bowes melanoma cDNA library and shown to couple through pertussis-toxin-sensitive Gi/Go proteins (Habert-Ortoli 1994). A second receptor, GalR2, was cloned shortly after (Bloomquist 1998), and GalR3 was identified the same year (Smith 1998; Kolakowski 1998). With three receptors mapped, attention turned to which fragments of galanin engage which receptor — work that established the N-terminal portion (residues 1–16/1–19) as the conserved receptor-binding region (Webling 2012).

What it does

When galanin binds GalR1, the receptor signals through inhibitory Gi/Go proteins, which lowers intracellular cAMP and dampens the activity of the host neuron (Habert-Ortoli 1994). At the system level, this translates to fewer action potentials in regions like the hippocampus, amygdala, and spinal cord — the same circuits that drive seizures and that carry pain signals. Because of this, galanin and its N-terminal fragments have been pursued as leads for anticonvulsant and analgesic drugs (Clynen 2014; Freimann 2015). The peptide also participates in feeding behavior, smooth muscle contractility, and somatosensory signaling through the broader galanin–receptor network (Kolakowski 1998; Gopalakrishnan 2021).

Mechanism

Galanin receptors are class A G-protein-coupled receptors. GalR1 and GalR3 signal predominantly through Gi/Go (lowering cAMP and opening inward-rectifier potassium channels, hyperpolarizing the neuron), while GalR2 couples through Gq/11 (raising intracellular calcium) (Webling 2012; Gopalakrishnan 2021). The N-terminal 1–16 region of galanin is conserved across species and is the primary determinant of receptor engagement; truncations and substitutions in this region have been used to build subtype-preferring ligands (Freimann 2015). The 19-residue fragment shown here covers that N-terminal recognition region but lacks the C-terminal residues (positions 20–30 of human galanin, beginning RSFS...) that contribute to full-length potency and to differential GalR2/GalR3 selectivity profiles (Webling 2012). The stored sequence is the bare amino-acid backbone; native galanin is C-terminally amidated, a modification that protects the C-terminus from carboxypeptidases and is not represented in the 19-letter sequence on this card.

Evidence

• Human: No human clinical trials of Galanin (1-19) itself. Galanin and galanin-receptor ligands have been reviewed as candidate targets for epilepsy and neurological disease, but no approved galanin-based drug exists (Clynen 2014; Freimann 2015).
• Animal: Galanin and N-terminal galanin analogs suppress seizure activity in rodent epilepsy models, summarized alongside other neuropeptides in anticonvulsant reviews (Clynen 2014).
• In vitro: Binding affinities of galanin and its fragments at cloned human GalR1, GalR2, and GalR3 have been characterized in radioligand assays from the receptor-cloning papers onward (Habert-Ortoli 1994; Bloomquist 1998; Smith 1998; Kolakowski 1998; Webling 2012; Freimann 2015).

Known effects

• Anticonvulsant activity — Preclinical (rodent seizure models, reviewed in Clynen 2014; Freimann 2015)
• Analgesia / reduced neuronal excitability — Preclinical, mechanistic (Habert-Ortoli 1994; Webling 2012)
• Modulation of feeding, hormone release, smooth-muscle activity — Documented for the parent galanin peptide (Kolakowski 1998; Gopalakrishnan 2021)

Regulatory status

• US: Not an approved drug. No FDA-approved galanin-receptor agonist or antagonist is on the market.
• EU: Not an approved drug.
• Research use: Galanin and its fragments are used as research reagents and as templates for medicinal-chemistry programs targeting GalR1/GalR2/GalR3 (Freimann 2015).

Related peptides

• Full-length human galanin — the parent 30-residue endogenous peptide that this 19-residue fragment is derived from (Kolakowski 1998; Webling 2012).
• Other galanin family ligands (galanin-message-associated peptide GMAP, galanin-like peptide GALP, alarin) — described in the assembled galanin–galanin-receptor signaling network (Gopalakrishnan 2021).