An endogenous neuropeptide and μ-opioid receptor agonist
Endomorphin 2 is an endogenous neuropeptide and μ-opioid receptor agonist (Ki = 0.69 nM) that has analgesic, negative reinforcing, and gastrointestinal properties.[1][2] It is found in the spinal cord and, to a lesser extent, in the brain. [3]? It is selective for μ- over δ- and κ-opioid receptors (Kis = 9,233 and 5,240 nM, respectively). [1] Endomorphin 2 also binds to mouse brain membranes and rat recombinant μ-opioid receptors expressed in CHO cells (Kis = 1.37 and 0.58 nM, respectively).[2] It inhibits cAMP accumulation induced by forskolin in CHO cells expressing rat recombinant μ-opioid receptors and in SH-SY5Y human neuroblastoma cells (IC50s = 7.08 and 7.76 nM, respectively).[4]? In mice, endomorphin 2 increases analgesia in a radiant heat tail-flick assay in mice following intracerebroventricular (i.c.v.) or intrathecal administration (ED50s = 1.99 and 3.81 μg, respectively) and induces conditioned place aversion when administered intracerebroventricularly at a dose of 10 μg. [2]It also decreases gastrointestinal transit time in mice when administered intracerebroventricularly at a dose of 3 μg.[2]
Reference:
[1]. Zadina, J.E., Hackler, L., Ge, L.J., et al. A potent and selective endogenous agonist for the μ-opiate receptor. Nature 386(6624), 499-502 (1997).
[2]. Goldberg, I.E., Rossi, G.C., Letchworth, S.R., et al. Pharmacological characterization of endomorphin-1 and endomorphin-2 in mouse brain. J. Pharmacol. Exp. Ther. 286(2), 1007-1013 (1998).
[3]. Martin-Schild, S., Gerall, A.A., Kastin, A.J., et al. Differential distribution of endomorphin 1- and endomorphin 2-like immunoreactivities in the CNS of the rodent. J. Comp. Neurol. 405(4), 450-471 (1999).
[4]. Harrison, C., McNulty, S., Smart, D., et al. The effects of endomorphin-1 and endomorphin-2 in CHO cells expressing recombinant μ-opioid receptors and SH-SY5Y cells. Br. J. Pharmacol. 128(2), 472-478 (1999).
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