Ontogenesis of cell surface mu-opioid ([3H]DAGO) binding sites in rat hypothalamus and ex vivo determination of blood-brain barrier penetration by opioid peptide FK 33-824.
Previous studies have demonstrated that the LH response to naloxone changes during development but the reason(s) for this are unknown. In the present work we have investigated the possibility that variations in cell surface opioid receptor levels (determined in tissue slice/punches) or changes in the ability of opioids to enter the CNS might be responsible. Opioid binding data indicate that both [3H]naloxone and [3H]DAGO-labelled binding sites remain at low levels until 10 days of age after which there is a progressive rise to adult levels at 15 days ([3H]DAGO) and 21 days ([3H]naloxone). Although several peaks and nadirs were observed in this detailed profile of receptor ontogeny, no exact correlation with the time course of LH response to opioid drugs was found. In an adaption of the slice binding assay we are able to quantify drug penetration into the brain (ex vivo binding). Ex vivo binding studies of blood-brain barrier (BBB) ontogeny indicate that there are changes with age in the ability of opioid peptides, injected subcutaneously, to inhibit binding at the mu-receptor. FK 33-824 induced a reduction in [3H]DAGO binding in the mediobasal hypothalamus until 15 days of age. FK in older rats had no effect on [3H]DAGO binding suggesting that formation of the BBB is complete at this age. In contrast, FK injection reduced binding in the median eminence-arcuate nucleus area (outside BBB) until 30 days of age. Surprisingly, this area also became refractory to FK injection after this age.(ABSTRACT TRUNCATED AT 250 WORDS)
Landymore
K M
KM
Department of Obstetrics and Gynecology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Wilkinson
M
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001812:Blood-Brain Barrier / Q000502:physiology*; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000378:metabolism* / Q000493:pharmacokinetics; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism*; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism*; D009270:Naloxone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism* / Q000502:physiology; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin