Insect neuropeptide leucopyrokinin analogues--synthesis and antinociceptive effect in rats.

The insect myotropic octapeptide leucopyrokinin Glp-Thr-Ser-Phe-Thr-Pro-Arg-Leu-amide (LPK or Lem-PK) (1) and its truncated analogues without the first N-terminal amino acids [2-8]-LPK (2) as well as devoid of the first, second and third N-terminal amino acids [4-8]-LPK (3) were prepared together with a series of the following modified [2-8]-LPK heptapetides such as: [Ala2] (4)-, [Ala3] (6)-, [D-Phe4] (7)-, [Ala5] (8)-, [D-Ala5] (9)-, [D-Thr5] (10)-, [Ser5] (11)-, [D-Pro6] (12)-, [Ala6] (13)- and [D-Arg7]-[2-8]-LPK (14) and [Pro1]-LPK (5). Bioassays were carried out by means of a hot-plate and a tail immersion tests in rats after i.c.v. and i.p. injections. Peptides 1 and 2 revealed prolonged high antinociceptive effects, while other peptides were practically inactive. [2-8]-LPK (2) probably crosses the blood-brain barrier in rats.

Central action of insect neuropeptide, periplanetin CC-1, in mice.

The central action of periplanetin CC-1 (Pea-HrTH) (Glp-Val-Asn-Phe-Ser-Pro-Asn-TrpNH2), octapeptide of the insect adipokinetic hormone family (AKH-family), isolated from American cockroach-Periplaneta americana, was studied in Albino Swiss mice (20-25 g). CC-1 was injected intracerebroventricularly (i.c.v.) in the volume of 5 microliters at the dose of 50 ng/mouse. It was found that CC-1 showed strong analgesic activity in "writhing syndrome" test and in "hot plate" test. In addition, periplanetin CC-1 decreased the threshold for tonic seizures and increased mortality in pentetrazole-induced seizures, having no influence on the electric convulsions. CC-1 is known to be a glucagon-like AKH in insects. However, administered i.c.v. to mice, it did not increase the peripheral blood glucose level. The obtained results indicate that periplanetin CC-1 shows a biological action in vertebrates, but its metabolic effects are different than in insects.