Protein kinase C in cyclic stretch-induced nerve growth factor production by urinary tract smooth muscle cells

Persson, Katarina; Sando, Julianne J.; Tuttle, Jeremy B.; Steers, William D.

doi:10.1152/ajpcell.1995.269.4.c1018

Cited by 75 publications

(60 citation statements)

References 23 publications

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“…Also, events such as inflammation and mechanical stretch of the bladder may do so (Persson et al 1995;Dmitrieva et al 1997). Thus, if the organs expressing elevated NGF in the SHR are subjected to stimuli from one or more of these sources, increased NGF may be a secondary response to the initial positive signal.…”

Section: N G F Metabolism In Shrsmentioning

confidence: 99%

The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males

Steers

Clemow

Persson

et al. 1999

Experimental Physiology

107

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SUMMARY Recent epidemiological studies have shown that hypertensive men are more likely to undergo surgical intervention for irritative voiding symptoms from BPH than age‐matched controls. Indeed, noradrenergic nerves which regulate vascular tone also participate in the functional component of bladder outlet obstruction due to BPH. Newer, less invasive therapies for BPH such as thermal therapy can relieve symptoms yet do not eliminate obstruction based on urodynamic studies. Coincidentally, drugs such as α‐adrenoceptor antagonists, which have been thought to relieve obstruction due to a peripheral effect, can be given intrathecally in animals to relieve urinary frequency due to obstruction. Taken together these observations implicate both peripheral and central sympathetic pathways in the motor control of the urinary bladder especially with disease states. We have used the hypertensive and behaviourally hyperactive spontaneously hypertensive rat (SHR), to investigate the roles sympathetic pathways or micturition. Elevated nerve growth factor (NGF) derived from vascular and bladder smooth muscle cells of the SHR appears to direct morphological, biochemical, and functional changes. The increase in NGF can apparently be explained by stabilization of its mRNA leading to increased synthesis of NGF. Bladders from SHRs develop a profuse noradrenergic hyperinnervation compared with the control WKY strain. Since afferents supplying the SHR bladder are hypertrophied, changes in afferent pathways are also likely. These differences in innervation and NGF in the SHR may explain changes in function. SHRs void 3 times as frequently as their genetic controls. Urinary frequency can be reduced by α‐adrenoceptor antagonists. Cystometrograms performed in SHRs reveal lower bladder capacities and micturition volumes and the presence of unstable contractions compared with the WKY rat. Intrathecal, rather than intra‐arterial administration of the α‐adrenoceptor antagonist doxazosin reduces unstable contractions in the SHR. In vitro muscle bath studies have shown enhanced responses of SHR bladder smooth muscle to α‐adrenoceptor agonists. It is likely that upregulation of NGF production causes sensory and possibly noradrenergic pathways to elicit hyperactive voiding. Increase in NGF in the adult bladder due to pathological conditions yields similar, yet distinct, consequences for voiding behaviour and innervation. Likewise, increased NGF in adult bladders following obstruction or inflammation triggers neuronal hypertrophy, enhanced reflex activity and urinary frequency. In contrast to the SHR, hyper‐innervation is not observed. Moreover, peripheral or spinal α‐adrenoceptor blockade eliminates urinary frequency following obstruction. These observations support the role for sympathetic pathways in the motor function of the bladder, especially in congenital or adult disease states. A similar process may underlie the neuroplasticity involved in alterations after obstruction or inflammation of the lower urinary tract in humans. The SHR strain ...

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Section: N G F Metabolism In Shrsmentioning

confidence: 99%

The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males

Steers

Clemow

Persson

et al. 1999

Experimental Physiology

107

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“…[24][25][26]. Based on this information the initial defect may be damage to nerves and a subsequent reduction Changes in nerve density have been reported in the obstructed bladder and associated with ageing in the in numbers.…”

Section: Muscle Hypertrophymentioning

confidence: 99%

Focal changes in nerve, muscle and connective tissue in normal and unstable human bladder

et al. 1999

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Objective To compare and quantify, in a morphological (91), 81 (20) and 74 (38) nerves/mm2 in the three defined areas, respectively. In the neuropathic tissues study, the changes that occur in the connective tissue elements (elastin and collagen), muscle fibre diameters the nerve profile densities were 672 (249), 57 (23) and 37 (28) nerves/mm2, respectively. Fibre diameter, and nerve densities between normal, idiopathic and neuropathic bladders.elastin and collagen content and nerve density were measured in normal and unstable bladder tissue using Materials and methods Bladder tissue was obtained from 27 patients undergoing cystectomy for carcithese three defined areas. The mean (sem) fibre diameter was 6.81 (0.52) in normal bladder; in idiopathic noma, from 12 with idiopathic instability and from seven neuropathic patients who were undergoing ileobladder tissue the fibre diameters in the three areas were 6.72 (0.62), 7.06 (0.62) and 7.34 (1.15) mm, cystoplasty. A combination of histochemical and immunohistochemical techniques were used to detect respectively, and in neuropathic bladders were 6.75 (0.62), 8.24 (0.62) and 9.35 (0.62) mm, respectively. detrusor muscle, connective tissue and nerve profiles in the bladder tissue.The relative areas of elastin were 0.79 (0.70), 0.56 (0.45) and 18.3 (4.1)% for the control, normal and Results In both idiopathic and neuropathic bladder tissue the structural changes were highly punctate. From aCected areas of the neuropathic bladders, respectively, and the relative areas of collagen were 3.5 (1.3), 6.15

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“…5 Mechanical stretch of cultured smooth muscle from the urinary tract elicits rapid accumulation of nerve growth factor messenger RNA followed by secretion of nerve growth factor protein. 6 Low-a nity NGFR immunoreactive ®bres in the human urinary bladder Wakabayashi et al 7 studied low-a nity nerve growth factor receptor (LNGFR) immunoreactive ®bres in the specimens obtained during urological surgery from the anterior wall of the bladder body of nine neurologically normal patients. LNGFR immunoreactive nerve ®bres were observed in the lamina propria, submucosal layer and muscle layer, but not in the epithelium.…”

Section: Introductionmentioning

confidence: 99%

p75 nerve growth factor receptor in the vesical urothelium of patients with neuropathic bladder: an immunohistochemical study

et al. 1998

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Introduction: Nerve growth factor (NGF), apart from its role as a growth factor, appears to be involved in neuroimmune interactions and in tissue in¯ammation. Low-a nity nerve growth factor receptor (p 75 NGFR), if demonstrated in the urothelium, could provide the means for (1) NGF-mediated modulation of the urothelial response to in¯ammation; (2) NGF-mediated autocrine/paracrine regulation of urothelial proliferation; and (3) p 75 NGFRmediated induction of apoptosis. Objectives: To investigate the presence of p 75 NGFR in the vesical urothelium of patients with neuropathic bladder by immunohistochemical methods. Setting: A hospital-based study of consecutive, unselected, adult patients of either sex with neuropathic bladder, undergoing procedure on the urinary tract in a Regional Spinal Injuries Centre located in the north-west of England. Intervention: Cold cup biopsies were taken from the trigone of the neuropathic urinary bladder of 26 patients with neuropathic bladder. Immunohistochemical studies were performed using antiNGF-receptor human monoclonal antibody which reacts with the low a nity receptor (p 75 NGFR). Results: Both neural and epithelial structures showed positive immunostaining for p 75 NGFR. The basal layer of the transitional epithelium showed strongly positive immunostaining for p 75 NGFR in all the 26 cases. The luminal layer of transitional epithelium showed varying degree of positive immunostaining in 12 patients. The nerve ®bres showed positive immunostaining for p 75 NGFR. In many cases, the positively-stained nerve ®bres were coursing very close to the basal layer of the urothelium almost entering the urothelium; however, no NGFR-positive intra-epithelial terminals could be seen. The positively-stained single nerve ®bres and positively-stained thicker nerve bundles were seen in abundance in the submucosa but they were present in a sparse manner in the muscularis layer. Conclusion: The presence of p 75 NGFR was demonstrated in the urothelium of neuropathic bladder of all the 26 patients with neuropathic bladder. This observation may have potential therapeutic implications.

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Protein kinase C in cyclic stretch-induced nerve growth factor production by urinary tract smooth muscle cells

Cited by 75 publications

References 23 publications

The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males

The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males

Focal changes in nerve, muscle and connective tissue in normal and unstable human bladder

p75 nerve growth factor receptor in the vesical urothelium of patients with neuropathic bladder: an immunohistochemical study

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