Oxytocin is a positive allosteric modulator of μ opioid receptor (MOR) signaling [1].?
Oxytocin, a 9-amine neuropeptide synthesized in the paraventricular nucleus (PVN) and the supraoptic nucleus of the hypothalamus, is secreted from the posterior pituitary into the systemic circulation, playing an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. Oxytocin has been reported to exert an?analgesic?effect as well [1].?
In hMOR-expressing HEK293 cells, Oxytocin alone showed no direct agonistic effect on human MOR at concentration up to 10-5 M, but treatment with 10-6 M Oxytocin markedly enhanced the MOR signaling stimulated by 10-6 M endomorphin-1, β-endorphin, morphine, fentanyl, as well as DAMGO. Moreover, in the competitive receptor-binding assay, 10-6 M Oxytocin did not alter the affinity of endomorphin-1 or morphine for MOR [1]. ?
Intracerebroventricular Oxytocin administration (0.2 μg) robustly increased medial nucleus accumbens shell (NAcSh) neuron mean firing rate in rats, but did not do so after rats were repeatedly treated with morphine [2].?
References:
[1]. Meguro Y, Miyano K, Hirayama S, et al. Neuropeptide oxytocin enhances μ opioid receptor signaling as a positive allosteric modulator. Journal of Pharmacological Sciences, 2018, 137(1): 67-75.
[2]. Moaddab M, Hyland B I, Brown C H. Oxytocin excites nucleus accumbens shell neurons in vivo. Molecular and Cellular Neuroscience, 2015, 68: 323-330.
