E-rosette formation by human lymphocytes incubated with sheep red blood cells (sRBC) is inhibited by morphine. We studied the ability of the opiate antagonists naloxone and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) to block this action. Active E-rosette formation by lymphocytes incubated with morphine was reduced from the control of 35.7±1.7% to 23.7±1.5% (p<0.001). Similarly, total E-rosette formation was reduced by morphine from the control of 65.8±1.3% to 53.2±2.9% (p<0.001). These effects were blocked by co-incubation of the lymphocytes with either Tyr-MIF-1 or naloxone (p<0.05). Tyr-MIF-1 was active (p<0.05) at concentrations as dilute as 10-13M. These results indicate that the neuropeptide Tyr-MIF-1 exerts an antiopiate effect at the human T-lymphocyte.

Because the tripeptide MIF-1 (Pro-Leu-Gly-NH2) is known to attenuate the effects of neuroleptic-induced catalepsy as well as neuroleptic-induced proliferation of dopamine (DA) receptors, we studied the related naturally occurring peptide, Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) for similar properties. Male rats were treated SC for 11 consecutive days with either the DA D1 receptor antagonist SCH 23390 HC1 (0.50 mg/kg per day), the DA D2 receptor antagonist spiperone HCl (0.30 mg/kg per day), or vehicle. Half the rats were cotreated daily with Tyr-MIF-1 (1.0 mg/kg per day). The cataleptic effects of SCH 23390 were not altered by Tyr-MIF-1. Tolerance to SCH 23390-induced catalepsy did not develop during the 11-day treatment, and Tyr-MIF-1 had no effect on SCH 23390-induced catalepsy. However, tolerance developed to spiperone-induced catalepsy, and Tyr-MIF-1 attenuated this development of tolerance (p < 0.001). Locomotor and stereotyped activities of the DA D1 and D2 agonists, SKF 39393 (3.0 mg/kg) and quinpirole (3.0 mg/kg) were not affected by Tyr-MIF-1 after treatment with the DA antagonists was discontinued. Tyr-MIF-1 did not alter the Bmax or Kd for in vitro binding of [3H]SCH 23390 and [3H]spiperone to homogenates of the striatum. These findings indicate that Tyr-MIF-1 is able to selectively affect the development of receptor tolerance to a DA D2 receptor antagonist, and that this effect is unrelated to changes in affinity or numbers of D2 receptors.

Our previous report showed that the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) blocks the inhibitory effect of morphine sulfate on E-rosette formation by human peripheral blood lymphocytes (PBL). In this study, additional in vitro effects of Tyr-MIF-1 on human PBL were studied. The percentages of positive cells for CD 2, a sheep erythrocyte receptor, CD 4 and CD 8 were unchanged after incubation of PBL with morphine or morphine plus Tyr-MIF-1. Tyr-MIF-1 was not mitogenic by itself. The addition of Tyr-MIF-1 did not increase the proliferative response of PBL to Con A, although morphine did. Tyr-MIF-1 did not activate PBL to produce IL 2 nor did it affect the production of IL 2 by Con A-stimulated PBL. The results suggest that Tyr-MIF-1 does not directly modulate CD 2, CD 4 and CD 8 expression, does not alter the proliferative response of PBL, and does not affect the production of IL 2.