Structure-activity relationships of mammalian bombesin-like neuropeptides in the contraction of rat uterus.
Various peptide derivatives of the C-terminal decapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB), i.e., carboxyl terminal fragments, amino terminal fragments and substituted analogues, were chemically synthesized and the structure-activity relationships of the peptides were investigated by comparing their contractile activities on the rat uterus. Peptides with chain lengths of 8 and 9 amino acid residues from the C-terminus of GRP-10 and NMB, respectively, had considerable contractile activities. At position 6 of both decapeptides, Val seems to be more favourable than Thr for inducing contraction of the rat uterus. The substitution of His at position 3 and Leu at position 9 of GRP-10 by Leu and Phe, as in NMB leads to a decrease in activity. Moreover, Trp at position 4 and -Met-NH2 at the C-terminus are essential for activity. Furthermore, in order to characterize the bombesin-receptor profile of rat uterus, the inhibitory effect of two peptide antagonists, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [Leu13-phi (CH2NH)-Leu14]-bombesin on the contraction of rat uterus were examined.
Institute of Applied Biochemistry, University of Tsukuba, Japan.
H
H
Mukai
H
H
Tanaka
K
K
Goto
K
K
Kawai
K
K
Yamashita
E
E
Munekata
D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects*
D010446:Peptide Fragments; C040794:neuromedin C; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin