(Tyr(0),Bpa(4))bombesin is a GRP receptor agonist.
(Tyr(0),Bpa(4))bombesin, (YB)BB was synthesized and its biologic activity evaluated using T47D breast cancer cells. ((125)I-Tyr(0), Bpa(4))BB bound with high affinity (K(d) = 5 nM) to T47D cells. Specific ((125)I-Tyr(0),Bpa(4))BB binding was inhibited with high affinity by BB, BW2258U89, GRP, GRP(14-27) and NMB (IC(50) values of 10, 2, 15, 20, and 150 nM)but not GRP(1-16) (IC(50) value of > 1000 nM). ((125)I-Tyr(0),Bpa(4))BB bound to the surface of T47D cells at 4 degrees C but was internalized at 37 degrees C. After binding at 4 degrees C followed by irradiation using ultraviolet light, ((125)I-Tyr(0),Bpa(4))BB labeled a 75 kDa protein using T47D cells. (Tyr(0),Bpa(4))BB, 10 nM, elevated cytosolic calcium using T47D cells within 10 s. Also (Tyr(0),Bpa(4))BB, 10 nM, elevated c-fos mRNA after 45 min. These results indicate that (Tyr(0),Bpa(4))BB is an agonist for GRP receptors.
Casibang
M
M
Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, Bldg. KWC, Rm. 300, 9610 Medical Ctr. Dr., 20850, Rockville, MD 20850, USA.
Moody
T W
TW
D000595:Amino Acid Sequence; D001839:Bombesin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D018004:Receptors, Bombesin / Q000819:agonists*; D014407:Tumor Cells, Cultured
D018004:Receptors, Bombesin; D001839:Bombesin