Which endogenous opioid peptide primarily binds to and activates the kappa (κ) opioid receptor, contributing to dysphoric effects?

Dynorphin is the primary endogenous opioid peptide that preferentially binds to and activates the kappa (κ) opioid receptor. Endogenous opioid peptides are naturally occurring substances in the body that interact with opioid receptors. Dynorphins are produced from a precursor molecule called prodynorphin. The kappa opioid receptor is one of the three main types of opioid receptors in the body, the others being mu (μ) and delta (δ). When dynorphin activates the kappa receptor, it triggers a cascade of intracellular events that can lead to various effects, including analgesia (pain relief) in some contexts, but it is also notably associated with dysphoria. Dysphoria is a state of unease, dissatisfaction, and general unhappiness. This contrasts with the euphoria often associated with mu (μ) opioid receptor activation. Therefore, dynorphin's activation of the kappa opioid receptor is significant because it contributes to negative emotional states, which distinguishes it from other endogenous opioid peptides that primarily activate the mu receptor and produce more rewarding effects.