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.
Plech
A
A
Department of Pharmacology, Silesian Medical Academy, Zabrze, Poland.
Rykaczewska-Czerwińska
M
M
Bartosz-Bechowski
H
H
Lombarska-Sliwińska
D
D
Małota
M
M
Szewczyk
M
M
Brus
R
R
Konopińska
D
D
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D009479:Neuropeptides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use*; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use*; D010146:Pain / Q000517:prevention & control*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000700:Analgesics; D009479:Neuropeptides; D009842:Oligopeptides; C049557:leucopyrokinin; D011761:Pyrrolidonecarboxylic Acid