(Tyr(0),Bpa(4))bombesin is a GRP receptor agonist

(Tyr(0),Bpa(4))bombesin, (YB)BB was synthesized and its biologic activity e valuated using T47D breast cancer cells. (I-125-Tyr(0),Bpa(4))BB bound with high affinity (K-d = 5 nM) to T47D cells. Specific (I-125-Tyr(0),Bpa(4))BB binding was inhibited with high affinity by BB, BW2258U89, GRP, GRP(14-27) and NMB (IC50 values of 10, 2, 15, 20, and 150 nM)but not GRP(1-16) (IC50 value of > 1000 nM). (I-125-Tyr(0),Bpa(4))BB bound to the surface of T47D c ells at 4 degrees C but was internalized at 37 degrees C. After binding at 4 degrees C followed by irradiation using ultraviolet light, (I-125-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),B pa(4))BB, 10 nM, elevated c-fos mRNA after 45 min. These results indicate t hat (Tyr(0),Bpa(4))BB is an agonist for GRP receptors. (C) 2000 Elsevier Sc ience Inc. All rights reserved.