Pharmacological activities of the MIF-1 analogues Pro-Leu-Gly, Tyr-Pro-Leu-Gly and pareptide.
The pharmacological activities of the related free acid analogues of MIF-1, Pro-Leu-Gly (PLG) and Tyr-Pro-Leu-Gly (YPLG), were investigated because of the possibility that they may be formed during the digestion of milk and wheat proteins in vivo. The amino acid sequences -Tyr-Pro-Leu-Gly- and -Pro-Leu-Gly- are present in proteins from these foods. Chronic administration of either PLG (0.25 mg/kg, SC, BID) or the control substance, pareptide (0.25 mg/kg, SC, BID), antagonized the development of tolerance to the cataleptic effects of haloperidol in mice. The effect of YPLG (0.25 mg/kg, SC, BID) on the development of this tolerance was borderline and not statistically significant. Nanomolar concentrations of PLG, YPLG, and pareptide each increased the in vitro binding of 3H-apomorphine to rat striatal receptors. In this in vitro system, bell-shaped dose response curves were observed for each peptide. The effects of these peptides on tolerance development and apomorphine binding are similar to those previously reported for MIF-1 and demonstrate that amidation at the carboxyl terminus is not required for biological activity.
D000818:Animals; D001058:Apomorphine / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced; D004361:Drug Tolerance; D006220:Haloperidol / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects
D011954:Receptors, Dopamine; C055208:tyrosyl-prolyl-leucyl-glycine; C055207:prolyl-leucyl-glycine; C024569:pareptide; D009075:MSH Release-Inhibiting Hormone; D006220:Haloperidol; D001058:Apomorphine