MECHANICAL STRETCH INCREASES SECRETION OF PARATHYROID HORMONE-RELATEDPROTEIN BY CULTURED BLADDER SMOOTH-MUSCLE CELLS

Parathyroid hormone-related protein (PTHrP) immunoreactivity has been detected in the bladder and increases in response to dilatation second ary to obstruction. The hypothesis that PTHrP could be increased solel y by stretch rather than other possible in vivo variables was tested b y stretching cultured bladder smooth muscle cells and analyzing the cu lture medium for this protein. In response to mechanical stretch, PTHr P was increased in smooth muscle cell cultures. Lmm Immunoradiometric assay revealed maximal rates of secretion for the first eight hours. C omparison of percent change in PTHrP secretion of flexed flexed cells for the various flex parameters revealed a difference (p = .006) when the degree of stretch (i.e. percent elongation) was altered. The prote in synthesis inhibitor cycloheximide inhibited basal and stretch-induc ed PTHrP secretion. PTHrP (1-100 nM) relaxed carbachol-contracted blad der body and base by 15% and 45% respectively. PTHrP did not affect bl adder contractions induced by potassium (124 mM) or alpha-beta MeATP ( 10 mu M). Increased PTHrP secretion in response to stretch of smooth m uscle raises the possibility of an autocrine action to relax the bladd er during filling. PTHrP may also exert a paracrine action on vessels regulating blood flow during bladder filling or it may modulate neural activity.