title: L-prolyl-L-leucyl-glycinamide analogues--a new class of peptide antihypertensives.
abstract: Accumulating evidence suggests that there is an increase in the density (maximum binding sites) of striatal dopamine receptors in the central nervous system of spontaneously hypertensive rats (SHR). A tripeptide of hypothalamic origin, PLG (L-Prolyl-L-Leucyl-Glycinamide) has been found to have modulatory effect on the dopamine receptors in the central nervous system of rats. Two analogues of PLG with cyclic amino-acid residues, L-Prolyl-L-Leucyl-(-)-thiazolidine-2-carboxamide and L-Prolyl-L-Leucyl-(+)-thiazolidine-2-carboxamide, have shown antihypertensive effect at the established phase of hypertension in 16-week old SHRs at a dose of 35 mg/kg per day per 7 days i.p. It was also observed from studies of radioligand [3H]-spiroperidol binding that the laevo-isomer of the PLG analogue has down-regulated the up-regulated dopamine receptors. Our findings confirm the role of central dopaminergic pathways in the pathogenesis of hypertension in SHR.
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D053778:Thiazolidines
chemical_list: D000959:Antihypertensive Agents; D053778:Thiazolidines; C052270:prolyl-leucyl-thiazolidine-2-carboxamide; D009075:MSH Release-Inhibiting Hormone