Modulation of agonist stimulated adenylyl cyclase and GTPase activity by L-pro-L-leu-glycinamide and its peptidomimetic analogue in rat striatal membranes

L-Prolyl-L-leucyl-glycinamide (PLG), also known as melanocyte-stimulating h ormone release inhibiting factor (MIF-1), is an endogenous brain tripeptide . Previous studies have shown that PLG, and its peptidomimetic analogues, r ender dopamine D-2 receptors more responsive to agonists by maintaining the high-affinity binding state of the receptors. In the present study, we exa mined the effect PLG and its analogue 3(R)-[(2(S)-pyrrolidylcarbonyl)amino] -2-oxo-I-pyrrolidinea-cetamide (PAOPA) on dopamine-stimulated adenylyl cycl ase 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)-stimulate d low K-m,GTPase activity was significantly increased by 1 mu M PLG or 1 nM PAOPA. These results suggest that PLG and PAOPA maintain the high affinity state of the D-2, receptor by increasing GTP hydrolysis through stimulatio n of agonist-induced GTPase activity. (C) 1999 Elsevier Science Ireland Ltd . All rights reserved.