Mechanical Stretch Increases Secretion of Parathyroid Hormone-Related Protein by Cultured Bladder Smooth Muscle Cells

Abstract

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

Effects of dimethyl sulphoxide and heparin on stretch‐activated ATP release by bladder urothelial cells from patients with interstitial cystitis

“…For the cell-stretch experiment, a Flexcell FX-2000 (Flexcell International Inc., McKeesport, PA, USA) unit was used to stretch a confluent culture of bladder urothelial cells. As described previously, there are several variables of stretch that can be varied in this model [11,14,15]. These include percentage elongation (or intensity of stretch), duration of stretch and duration of rest between stretching.…”

The preterm parturition syndrome

“…298 The effect of stretch increases in late gestation and is maximal during labour as a consequence of the relative reduction in uterine growth compared with fetal growth and of the declining circulating and/or local concentrations of progesterone. 298,300,301 The effect of mechanical forces on muscle has been studied extensively in myocardium, 302 vascular smooth muscle, 303 bladder, 304 and gastrointestinal smooth muscle 305 but not in myometrium.…”

Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells

“…17). To identify a mechanistic link between mechanical stimulation and growth of bladder muscle, several groups including our own have investigated the expression of known smooth muscle cell (SMC) mitogens and other growth regulatory molecules in bladder SMC following overdistension secondary to bladder outlet obstruction in vivo or in response to repetitive mechanical stimulation in vitro (5,6,8,9,30,32,38,40).…”

“…Although bladder distension and mechanical stretch of bladder SMC in vitro has been shown to alter expression of discrete sets of genes (5,6,8,9,30,32,38,40), it remains to be determined whether stretch induces extensive or limited changes in gene expression in bladder SMC. To address this question, we have undertaken a large-scale DNA array analysis of primary culture human bladder SMC subjected to cyclic stretch-relaxation.…”