An-zhong Zhang, Jaw-Kang Chang, G. Pasternak
Jun 22, 1981
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Influential Citations
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Quality indicators
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Life sciences
Abstract
Abstract Active in both binding and biological assays, morphiceptin (NH 2 Tyr-Pro-Phe-Pro-CONH 2 ), a potent opioid peptide derivative of β-casamorphine, binds specifically and selectively to mu or morphine-type receptors with little affinity for delta sites. Displacement studies of a variety of 3 H-labeled opiates and enkephalins show biphasic curves. Naloxazone, which blocks irreversibly and selectively high affinity opiate and enkephalin binding, abolishes morphiceptin's inhibition of binding at low concentrations, suggesting that the high affinity binding of enkephalins and opiates represents a mu or morphine-type receptor. Unlike the reversible antagonist naloxone, naloxazone treatment in vivo inhibits for over 24 hours the analgesic activity of morphiceptin like it inhibits morphine, β-endorphin and enkephalin analgesia. Together, these studies imply that opiates and enkephalins bind with highest affinity to a mu receptor which mediates their analgesic activity. The 3 H-D-ala 2 -D-leu 5 -enkephalin binding remaining after naloxazone treatment, representing a lower affinity site (K D 4 nM), is quite insensitive to morphiceptin inhibition and has the characteristics of a delta receptor. However, the 3 H-dihydromorphine binding present after naloxazone treatment, which also represents a lower affinity site (K D 6 nM), is far more sensitive to both morphine and morphiceptin and may represent a second morphine-like, or mu, receptor.