Inhibition of analgesia by C-terminal deletion analogs of human beta-endorphin.
Human beta-endorphin (beta h-EP) analogs of variable chain lengths have been investigated for their potency in inhibiting analgesia induced by beta h-EP or by the potent opiate etorphine. It was found that beta h-EP-(1-28) inhibits the analgesic effect of beta h-EP and etorphine when co-injected intracerebroventricularly into mice. Antagonism by competition at same opioid receptor subtypes is suggested from parallel shifts of the dose-response curve of etorphine or beta h-EP in the presence of increasing doses of beta h-EP-(1-28). On a molar basis, beta h-EP-(1-28) is nearly 10 times more potent than naloxone. The reduction of the chain length from residues 1-28 to 1-27 lowered the antagonist potency while further reduction of the peptide chain led to a complete loss of inhibitory activity. From comparison of the opioid-receptor binding affinity, analgesic activity and antagonist potency, it is concluded that the C-terminus of beta-EP is critical to the biological efficacy of the molecule and that the antagonist activity of C-terminal deletion analogs is probably mediated through residues 27 and 28.
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D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D004723:Endorphins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D005048:Etorphine / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D001615:beta-Endorphin
D000700:Analgesics; D004723:Endorphins; D010446:Peptide Fragments; D011957:Receptors, Opioid; D009270:Naloxone; D005048:Etorphine; D001615:beta-Endorphin