Weaning-induced development of delta-opioid receptors in rat brain: differential effects of guanine nucleotides and sodium upon ligand-receptor recognition.
1. We have previously shown that weaning at day 21 increases delta-opioid receptor binding in the brain at day 25, which might be due to stimulation of the development of a delta-opioid receptor subtype or activation of G-protein coupling processes. 2. We have addressed the possibility that weaning stimulates coupling of the delta-receptor by homogenate binding studies with four agonist and one antagonist radioligand in the presence of a GTP analogue and Na+ in brain tissue from weaned and non-weaned animals. 3. Saturation studies with three agonist ligands ([3H]-deltorphin I, [3H]-S-Atc-Ile(5,6)deltorphin I and [3H]-R-Atc-Ile(5,6)deltorphin II) showed higher levels of maximal binding in brains from 25-day weaned than in brains from non-weaned rats. The magnitude of the effects of GMPPNP and Na+ in decreasing this binding was ligand dependent and in each case was significantly more marked in brains from weaned animals. GMPPNP and Na+ were completely without effect on Bmax for, [3H]-S-Atc-Ile(5,6)deltorphin I and [3H]-R-Atc-Ile(5,6)deltorphin II in brains from non-weaned rats. 4. [3H]-Ile(5,6)deltorphin II and [3H]-naltrindole showed no differences in labelling between weaned and non-weaned groups and both groups responded similarly to the effects of GMPPNP and Na+ treatment. 5. GMPPNP and Na+ had small effects on binding affinity (K(D)) for some of the agonist radioligands which were similar in both weaned and non-weaned groups. 6. Weaning induced increases in binding of delta-receptors in 25-day rats can be explained in terms of the way delta-agonist radioligands recognize the receptor environment.
Kelly
M D
MD
Pharmacology Research Group, School of Biological Sciences, University of Surrey, Guildford.
Hill
R G
RG
Borsodi
A
A
Toth
G
G
Kitchen
I
I
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008024:Ligands; D009271:Naltrexone / Q000031:analogs & derivatives / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000096:biosynthesis*; D012964:Sodium / Q000378:metabolism*; D014886:Weaning
D008024:Ligands; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C060208:deltorphin I, Ala(2)-; C060209:deltorphin II, Ala(2)-; D006165:Guanylyl Imidodiphosphate; D009271:Naltrexone; D012964:Sodium; C055382:naltrindole