D-Arg1,D-Phe5,D-Trp7,9,Leu11 substance P, a neuropeptide antagonist, blocks binding, Ca2(+)-mobilizing, and mitogenic effects of endothelin and vasoactive intestinal contractor in mouse 3T3 cells
- Imperial Cancer Research Fund, London (England)
Endothelin (ET1) and vasoactive intestinal contractor (VIC) stimulate quiescent Swiss 3T3 cells to resume DNA synthesis acting synergistically with epidermal growth factors (EGF) and other mitogens. The peptide (D-Arg1,D-Phe5,D-Trp7,9,Leu11) substance P has been identified as a broad spectrum neuropeptide antagonist which blocks the binding and biological effects of the Ca2(+)-mobilizing neuropeptides bombesin, vasopressin, and bradykinin. In the present study we show that (D-Arg1,D-Phe5,D-Trp7,9,Leu11) substance P also acts as an ET1/VIC antagonist as judged by the following criteria: (a) inhibition of specific 125I-labelled ET1 binding to a ET1/VIC receptor in a competitive and dose-dependent manner; (b) blocking of the rapid increase in the cytosolic Ca2+ concentration promoted by ET1 or VIC; and (c) inhibition of DNA synthesis stimulated by VIC in the presence of EGF. The inhibitory effects of (D-Arg1,D-Phe5,D-Trp7,9,Leu 11) substance P on Ca2+ mobilization and DNA synthesis were reversed by increasing the concentration of VIC. This is the first time that a peptide structurally unrelated to ET1 or VIC is shown to block the binding and mitogenic effects of peptides of the endothelin family.
- OSTI ID:
- 6325832
- Journal Information:
- Journal of Cellular Physiology; (USA), Journal Name: Journal of Cellular Physiology; (USA) Vol. 145:1; ISSN 0021-9541; ISSN JCLLA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CALCIUM COMPOUNDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
FIBROBLASTS
GROWTH FACTORS
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MICE
MITOGENS
NUCLEI
NUCLEIC ACID REPLICATION
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES