Characterization of the inhibitory effect of adrenocorticotropin/melanocyte-stimulating hormone-like peptides on the binding of dopamine receptor ligands to the dopamine D2 receptor in vitro.
Adrenocorticotropin (ACTH)-(1-24) decreased the binding of the dopamine D2 agonist [3H]N-n-propylnorapomorphine [3H](NPA) to the dopamine D2 receptor in rat striatal membranes in vitro. The association and dissociation of [3H]NPA to the dopamine D2 receptor was inhibited by ACTH-(1-24), suggesting an apparent competitive interaction between ACTH-(1-24) and the binding of [3H]NPA. ACTH-(1-24) was able to inhibit the binding of the dopamine D2 receptor antagonist [3H]spiperone to the dopamine D2 receptor, both in the high- and the low-affinity state. These observations suggest a G-protein-independent mechanism of action. The inhibitory effect of ACTH-(1-24) and ACTH-(7-16)-NH2 was diminished after the addition of polylysine chains, presumably via a blockade of the attachment sites for ACTH-(1-24) on the dopamine D2 receptor. The effect of ACTH-(1-24) on membrane fluidity and on the inhibition of the binding of [3H]NPA to the dopamine D2 receptor appeared to be unrelated because lowering the incubation temperature from 25 degrees C to 4 degrees C, which causes a strong decrease of membrane fluidity, did not diminish the effect of ACTH-(1-24) on the binding of [3H]NPA to the dopamine D2 receptor. Furthermore, in both young and old rats, whose membranes are reported to differ in lipid composition and membrane fluidity, ACTH-(1-24) inhibited the binding of [3H]NPA to the dopamine D2 receptor to nearly the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)
Florijn
W J
WJ
Department of Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht.
De Boer
T
T
Tonnaer
J A
JA
Versteeg
D H
DH
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000367:Age Factors; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D001667:Binding, Competitive; D065127:Dopamine D2 Receptor Antagonists; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010455:Peptides; D017448:Receptors, Dopamine D2; D006165:Guanylyl Imidodiphosphate; D013134:Spiperone; C009074:N-n-propylnorapomorphine; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D001058:Apomorphine