In an attempt to determine the mechanism by which the tripeptide l-prolyl-l-leucyl-glycine amide (PLG, MIF-I) exerts its antiparkinsonian effect, the action of this substance on various postsynaptic components of striatal dopaminergic nerves was studied. It was shown that injection of rats with MIF-I (1 mg/kg, IP×5, 24 hr intervals) did not alter tyrosine hydroxylase, dopa decarboxylase, choline acetyltransferase and glutamic acid decarboxylase activities in the striatum under the conditions tested. The activities of adenylate cyclase, dopamine-stimulated adenylate cyclase, and guanylate cyclase were not altered in vitro by various concentrations of MIF-I (0.1 to 1000 μM), although VIP and neurotensin had some effect. Also the rate of uptake of 3H-dopamine by rat striatal synaptosomes was unchanged, as was the binding of 3H-dopamine and 3H-spiperone to beef caudate membranes. This series of studies indicates that MIF-I does not act directly on the striatal dopamine postsynaptic receptor under the conditions tested, although it is possible that MIF-I could act indirectly at this or another site in vivo by releasing or activating some other factor.

Because of conflicting reports of the actions of the antiparkinsonian agent L-prolyl-L-leucyl-glycine amide (PLG, MIF-I) on the turnover of Striatal dopamine (DA), this process was reinvestigated. In the present series of studies, it was found that neither our MIF-I (200 ng ICV) nor the MIF-I used by Versteeg et al. [25]was effective in altering the rate of decline of endogenous DA in the caudate nucleus of rats pretreated with α-methyl-p-tyrosine (300 mg/kg IP). In addition, our MIF-I (1 mg/kg IP) did not change endogenous dihydroxyphenylacetic acid (DOPAC) or homovanillic acid (HVA) in rat striatum. These studies indicate that MIF-I does not alter the turnover rate of DA in nigrostriatal neurons. It is possible that MIF-I or some substance released by MIF-I acts at a posfsynaptic receptor site.