REGULATION OF NERVE GROWTH-FACTOR SECRETION IN SMOOTH-MUSCLE CELLS CULTURED FROM RAT BLADDER BODY, BASE AND URETHRA

Purpose: Interest in the regulation of nerve growth factor (NGF) produ ction in the urinary tract derives from its probable involvement in ob structive, inflammatory and developmental disorders. This study examin es receptor-mediated stimuli that alter NGF production in cells of the lower urinary tract. Materials and Methods: Cells were isolated and c ultured from the bladder body, base and urethra, confirmed as smooth m uscle type by alpha-actin expression, and examined for growth rate and NGF secretion in response to autonomic agonists, cytokines, neuropept ides and growth factors. NGF secreted into the culture medium was quan titated via 2-site enzyme-linked immunoassay. Regional tissue contents of NGF and norepinephrine (NE) were also measured. Only statistically significant differences (Student's t test, p < 0.05) are reported. Re sults: Cultured urinary tract cells derived from different regions var ied in growth rate and NGF secretory activity. Bladder body secreted l ess NGF than base, and base less than urethra. A similar gradient in g rowth rate occurred in vitro, with urethral cells most active. However , no regional differences were found in bladder tissue NGF content des pite significant variations in NE levels. Platelet-derived growth fact or (PDGF) and transforming growth factor-beta (TGF-beta) were among th e most potent stimuli to NGF production by cultured cells while cAMP l inked receptors and eicosinoids inhibited NGF output. Conclusions: A c omplex system of regionally specific and stimulus-specific control reg ulates the production of NGF by urinary tract cells. While tissue leve ls of NGF do not correlate with the density of noradrenergic innervati on, bladder innervation is sufficiently dynamic to respond to changes in NGF production and to participate in pathophysiology.