Activation of B2 bradykinin receptors by neurotensin.
Many previous reports suggested that relatively high concentrations of neurotensin were required to exert its effects on neurotransmitter secretion. The neurotensin binding sites, which recognize high concentrations of neurotensin, were characterized in rat pheochromocytoma (PC12) cells. When PC12 cells were treated with neurotensin, [3H]norepinephrine secretion and elevation of cytosolic calcium were evoked at EC(50) values of 59+/-4 and 37+/-7 microM, respectively. Both calcium release and inositol 1,4,5-trisphosphate (IP(3)) production induced by neurotensin suggested involvement of phospholipase C. Experiments with simultaneous or sequential treatment with neurotensin and bradykinin suggested that neurotensin and bradykinin act on the same binding sites. Furthermore, both inhibition of bradykinin- and neurotensin-induced calcium rises by bradykinin receptor antagonists with similar IC(50) values and receptor binding analysis using [3H]bradykinin confirmed that neurotensin directly binds to B2 bradykinin receptors. The data suggest that neurotensin binds and activates the B2 bradykinin receptors.
Park
Tae-Ju
TJ
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea.
Kim
Kyong-Tai
KT
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009496:Neurotensin / Q000031:analogs & derivatives / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000502:physiology
D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D009496:Neurotensin; D010738:Type C Phospholipases; D001920:Bradykinin; D002118:Calcium; D009638:Norepinephrine