Histamine,Norepinephrine,and Bradykinin Stimulation of Fibroblast Growth and Modification of Serotonin Response 1

Summary

Histamine and norepinephrine have a concentration-dependent growth-enhancing effect on fibroblast growth in vitro that is different from the response to serotonin. These distinct dose-response curves suggest different mechanisms of action. Furthermore, histamine depresses growth of human embryo lung fibroblasts while enhancing growth of an established cell line (3T6) and serially cultured strains of mouse skin fibroblasts. The acquired nature of the histamine response is in contrast to the consistent growth-enhancing effect of serotonin and norepinephrine on all fibroblast lines or strains.

At micromolar concentrations, histamine, norepinephrine, and bradykinin antagonize the action of serotonin, while at a nanomolar level norepinephrine potentiates the effect of serotonin. The spatial configuration of bradykinin is critical for the fibroblast growth response. Prostaglandin E₂ inhibits fibroblast growth.

The authors gratefully acknowledge the assistance of Mr. T. Ralph Alvarez and the gift of prostaglandin E₂ from Dr. Vincent A. Ziboh.