Regulation of Nerve Growth Factor Secretion in Smooth Muscle Cells Cultured from Rat Bladder Body, Base and Urethra

Abstract

Purpose Interest in the regulation of nerve growth factor (NGF) production in the urinary tract derives from its probable involvement in obstructive, inflammatory and developmental disorders. This study examines receptor-mediated stimuli that alter NGF production in cells of the lower urinary tract. Materials and Methods Cells were isolated and cultured from the bladder body, base and urethra, confirmed as smooth muscle type by alpha-actin expression, and examined for growth rate and NGF secretion in response to autonomic agonists, cytokines, neuropeptides and growth factors. NGF secreted into the culture medium was quantitated 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. Results Cultured urinary tract cells derived from different regions varied in growth rate and NGF secretory activity. Bladder body secreted less NGF than base, and base less than urethra. A similar gradient in growth rate occurred in vitro, with urethral cells most active. However, no regional differences were found in bladder tissue NGF content despite significant variations in NE levels. Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) were among the most potent stimuli to NGF production by cultured cells while cAMP linked receptors and eicosinoids inhibited NGF output. Conclusions A complex system of regionally specific and stimulus-specific control regulates the production of NGF by urinary tract cells. While tissue levels of NGF do not correlate with the density of noradrenergic innervation, bladder innervation is sufficiently dynamic to respond to changes in NGF production and to participate in pathophysiology.