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

Ram K. Mishra, Maynard H. Makman, Willard J. Costain, Venugopalan D. Nair, Rodney L. Johnson

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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-I-pyrrolidineacetamide (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 K(m) GTPase activity was significantly increased by 1 μM 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.

Original languageEnglish (US)
Pages (from-to)21-24
Number of pages4
JournalNeuroscience Letters
Volume269
Issue number1
DOIs
StatePublished - Jul 2 1999

Keywords

  • Adenylyl-cyclase
  • D receptor
  • Dopamine
  • GTPase
  • L-Prolyl-L-leucyl- glycinamide
  • Rat
  • Striatum

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