Receptor selectivity of Met-enkephalin-Arg6-Phe7, an endogenous opioid peptide, in cerebral cortex of human and rat.
This study was undertaken to examine the receptor selectivity of Met-enkephalin-Arg6-Phe7 (MERF) employing radioreceptor binding assays in human cerebral cortex membranes, and to elucidate the responsible receptors that mediate the regulatory action of MERF on high (20 mM) K+-stimulated release of [3H]norepinephrine ([3H]-NE) in rat cortex slices. Specific binding of [3H]MERF was inhibited by DAMGO, Tyr-D-Arg-Phe-Sar(TAPS), bremazocine and ethylketocyclazocine (EKC), but not by U69,593 (U69) and DPDPE. MERF showed high affinity for specific binding sites of [3H]DAMGO. However, MERF had little influence on the specific binding of [3H]DPDPE, [3H]U69 and [3H]diprenorphine ([3H]DIP) in the presence of 1 microM each of DAMGO, DPDPE and U69. In [3H]NE release experiments using rat cortex slices, DAMGO, MERF and EKC, in order of their potency, inhibited K+-stimulated release of [3H]NE. The inhibitory effects of MERF and DAMGO were more sensitive than that of EKC to antagonism by CTAP, nor-binaltorphimine (nor-BNI) and naloxone. These results suggested that MERF possesses high affinity for mu-receptors, but not for delta-, kappa1-, and very low affinity for kappa2-receptors in human cerebral cortex membranes. Also, the inhibitory effect of MERF on the K+-stimulated release of [3H]NE appears to be mediated by mu-receptors in rat cerebral cortex slices.
Kim
K W
KW
Dept. of Pharmacology, Chonbuk University Medical School, Chonju, Republic of Korea. keewon@moak.chonbuk.ac.kr
Woo
R S
RS
Kim
C J
CJ
Cheong
Y P
YP
Kim
J K
JK
Kwun
J
J
Cho
K P
KP
D000328:Adult; D000818:Animals; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000494:pharmacology; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000378:metabolism; D016314:Ethylketocyclazocine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013004:Somatostatin
D044482:Benzeneacetamides; D001575:Benzomorphans; C529311:CTAP octapeptide; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D011759:Pyrrolidines; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C051844:norbinaltorphimine; D013004:Somatostatin; D004744:Enkephalin, Methionine; D016314:Ethylketocyclazocine; D009271:Naltrexone; C027511:enkephalin-Met, Arg(6)-Phe(7)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C053418:tyrosyl-arginyl-phenylalanyl-sarcosine; C027248:bremazocine; C045444:U 69593; D009638:Norepinephrine