Evidence for the presence of mu- and kappa- but not of delta-opioid sites in the human fetal brain.
The presence of multiple opioid binding sites in human fetal brain at 20 weeks gestational age was determined using the following selective tritiated ligands: D-Ala2, N-MePhe4, Gly-ol5-enkephalin (DAGO) for the mu-type, D-Pen2, D-Pen5-enkephalin (DPDP) for the delta-type and U-69,593 for the kappa-type. [3H]DAGO and [3H]U-69,593 each bind to a single class of high-affinity sites in membrane preparations with respective Kd values of 0.96 +/- 0.33 nM and 0.57 +/- 0.20 nM. The binding capacity for [3H]DAGO is 1.38 +/- 0.21 pmol/g tissue whereas [3H]U-69,593 has a binding capacity of 1.04 +/- 0.22 pmol/g tissue. Using DPDP we did not detect any specific high-affinity binding sites in human fetal brain. The non-selective tritiated opioid ethylketazocine (EKC) labels a homogenous class of sites with a Kd of 0.17 +/- 0.01 nM and a binding capacity of 2.15 +/- 0.15 pmol/g tissue, a value that is not statistically different from the total capacity obtained with [3H]DAGO and [3H]U-69,593. Competition studies using selective unlabeled opioids against the binding of [3H]-DAGO, [3H]U-69,593 or [3H]EKC indicate that opioid sites present in human fetal brain possess similar pharmacological characteristics to those found in human and mammalian adult brain. The results of this study present the first evidence for the presence of mu- and kappa-type opioid sites in human fetal brain and this may support the postulated role of the opioid system in the neurobiological development.
Magnan
J
J
Département de Pharmacologie, Université de Montréal, Que., Canada.
Tiberi
M
M
D044482:Benzeneacetamides; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma
D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593