Signalling pathway
Follow orexin-A and orexin-B from their shared precursor to two receptors, and distinguish receptor activation from blockade.
Updated: 2026-09-14
| Molecule | Type | Receptor / target | Relation | Evidence class | Sources |
|---|---|---|---|---|---|
| Orexin-A | Endogenous ligand | OX1Orexin receptor type 1 | AgonistCanonical endogenous agonismGq / phosphoinositide–calcium signaling | Curated receptor pharmacology | 1 |
| Orexin-B | Endogenous ligand | OX1Orexin receptor type 1 | AgonistCross-pharmacologyLower-affinity receptor activation; context-dependent G protein signaling | Curated receptor pharmacology | 12 |
| Orexin-A | Endogenous ligand | OX2Orexin receptor type 2 | AgonistCanonical endogenous agonismGq/11 and Gi/o coupling | Curated receptor pharmacology | 1 |
| Orexin-B | Endogenous ligand | OX2Orexin receptor type 2 | AgonistCanonical endogenous agonismGq/11 and Gi/o coupling | Curated receptor pharmacology | 1 |
Each edge below comes from an agent-specific source. Status and receptor pharmacology are verified separately.
| Molecule | Type | Receptor / target | Relation | Evidence class | Sources |
|---|
HCRT produces a precursor that is processed into orexin-A and orexin-B. Their sequences and modifications differ. The map shows the mature peptides; the initial Q in the orexin-A sequence represents the residue converted to pyroglutamate, as specified under modifications. Source (opens in a new tab).
OX1 has higher affinity for orexin-A than for orexin-B. OX2 responds to both peptides and can couple to different G proteins. A connection in this map shows receptor pharmacology, not equal potency or identical behavioral effects. The discovery feeding experiments were in rats. OX1 (opens in a new tab) · OX2 (opens in a new tab) · Discovery study (opens in a new tab).
An agonist activates a receptor; an antagonist blocks activation. These directions must stay separate when interpreting sleep and wakefulness claims. Human experiments using orexin-A do not automatically establish the same result for orexin-B, another route or a receptor-targeting drug. Read the individual article for the tested population and outcome.