title: Modulation of agonist stimulated adenylyl cyclase and GTPase activity by L-pro-L-leu-glycinamide and its peptidomimetic analogue in rat striatal membranes.
abstract: L-prolyl-L-leucyl-glycinamide (PLG), also known as melanocyte-stimulating hormone release inhibiting factor (MIF-1), is an endogenous brain tripeptide. Previous studies have shown that PLG, and its peptidomimetic analogues, render dopamine D2 receptors more responsive to agonists by maintaining the high-affinity binding state of the receptors. In the present study, we examined the effect PLG and its analogue 3(R)-[(2(S)-pyrrolidylcarbonyl)amino]-2-oxo-1-pyrrolidineacetam ide (PAOPA) on dopamine-stimulated adenylyl cyclase and NPA-stimulated GTPase activity in rat striatal membranes. Dopamine-stimulated adenylyl cyclase activity was inhibited by both PLG and PAOPA in a dose-dependent manner, whereas R(-)-propylnorapomorphine (NPA)-stimulated low Km GTPase activity was significantly increased by 1 microM PLG or 1 nM PAOPA. These results suggest that PLG and PAOPA maintain the high affinity state of the D2 receptor by increasing GTP hydrolysis through stimulation of agonist-induced GTPase activity.
authors.affiliation: Department of Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, Ontario, Canada. mishrar@fhs.mcmaster.ca
authors.forename: R K
authors.initials: RK
authors.lastname: Mishra
authors.forename: M H
authors.initials: MH
authors.lastname: Makman
authors.forename: W J
authors.initials: WJ
authors.lastname: Costain
authors.forename: V D
authors.initials: VD
authors.lastname: Nair
authors.forename: R L
authors.initials: RL
authors.lastname: Johnson
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006727:Hormone Antagonists / Q000378:metabolism; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives / Q000378:metabolism*; D017072:Neostriatum / Q000201:enzymology* / Q000648:ultrastructure; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D011760:Pyrrolidinones / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013347:Subcellular Fractions
chemical_list: D006727:Hormone Antagonists; D011760:Pyrrolidinones; D017448:Receptors, Dopamine D2; C067487:3-(N-prolylamine)-2-oxo-1-pyrrolidineacetamide; D009075:MSH Release-Inhibiting Hormone; D020558:GTP Phosphohydrolases; D000262:Adenylyl Cyclases; D004298:Dopamine