title: Interaction of L-prolyl-L-leucyl glycinamide with dopamine D2 receptor: evidence for modulation of agonist affinity states in bovine striatal membranes.
abstract: The role of the hypothalamic tripeptide L-prolyl-L-leucyl-glycinamide (PLG) in modulating the agonist binding to bovine striatal dopamine D2 receptor was investigated using a selective high-affinity agonist, n-propylnorapomorphine (NPA). PLG caused an enhancement in [3H]NPA binding in striatal membranes in a dose-dependent manner, the maximum effect being observed at 10(-7)-10(-6) M concentration of the tripeptide. The Scatchard analysis of [3H]NPA binding to membranes preincubated with 10(-6) M PLG revealed a significant increase in the affinity of the agonist binding sites. In contrast, there was no effect of PLG on the binding pattern of the antagonist [3H]spiroperidol. The antagonist versus agonist competition curves analyzed for agonist high- and low-affinity states of the receptor displayed an increase in the population and affinity of the high-affinity form of the receptor with PLG treatment. The low-affinity sites concomitantly decreased with relatively small change in the affinity for the agonists. Almost similar results were obtained when either NPA or apomorphine was used in the competition experiments. A partial antagonistic effect of PLG on 5'-guanylylimidodiphosphate [Gpp(NH)p]-induced inhibition of high-affinity agonist binding was also observed, as the ratio of high- to low-affinity forms of the receptor was significantly higher in the PLG-treated membranes compared to the controls. Direct [3H]NPA binding experiments demonstrated that PLG attenuated the Gpp(NH)p-induced inhibition of agonist binding by increasing the EC50 of the nucleotide (concentration that inhibits 50% of the specific binding). No effect of PLG on high-affinity [3H]NPA binding, however, could be observed when the striatal membranes were preincubated with Gpp(NH)p.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D002417:Cattle; D003342:Corpus Striatum / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D009994:Osmolar Concentration; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
chemical_list: D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D006165:Guanylyl Imidodiphosphate; D013134:Spiperone; C009074:N-n-propylnorapomorphine; D009075:MSH Release-Inhibiting Hormone; D001058:Apomorphine