Inhibitory effect of neuropeptide Y on adrenergic and cholinergic transmission in rat urinary bladder and urethra

1994 ◽  
Vol 266 (4) ◽  
pp. R1411-R1417 ◽  
Author(s):  
L. V. Tran ◽  
G. T. Somogyi ◽  
W. C. De Groat

The effects of porcine neuropeptide Y (NPY) on electrically evoked release of [3H]norepinephrine ([3H]NE) and [3H]acetylcholine ([3H]ACh) were investigated in isolated preparations of the rat lower urinary tract. In the urethra, NPY (0.02-0.5 microM) decreased the release of [3H]NE in a dose-dependent manner (10-53%). In the bladder base the inhibitory effect of NPY on [3H]NE release was not dose dependent. A low concentration (0.1 microM) decreased the release (38%), whereas a high concentration (0.5 microM) had no effect. However, in atropine-treated preparations, 0.5 microM NPY elicited a significant inhibition (43%). These observations suggest that 0.5 microM NPY elicits two opposing actions: a direct inhibitory action on adrenergic terminals and an indirect disinhibitory action to eliminate heterosynaptic cholinergic inhibition of [3H]NE release. In both tissues the action of NPY on [3H]NE release was not significantly modified by the alpha-adrenergic blocking agent yohimbine (1 microM). [3H]ACh release in the bladder body was not altered by 0.1 microM NPY but was suppressed (39%) by 1 microM NPY. The effect of NPY (1 microM) on [3H]ACh release was dependent on the frequency of stimulation. NPY suppressed the release at 2-Hz stimulation but had no significant effect at 20 Hz. These results suggest that NPY may have an important role in the neural regulation of the lower urinary tract by exerting differential effects on the release of cholinergic and adrenergic transmitters via autoinhibition and heterosynaptic interactions.

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takaki Mizusawa ◽  
Noboru Hara ◽  
Kenji Obara ◽  
Etsuko Isahaya ◽  
Yuki Nakagawa ◽  
...  

Objectives. To examine the feature of men who benefit from dose escalation of naftopidil for lower urinary tract symptoms (LUTSs).Methods. Based on the IPSS, men reporting LUTS were prospectively studied using 50 mg/day of naftopidil for the first 4 weeks; satisfied patients continued its 50 mg/day (), and those reporting unsatisfactory improvement received its 75 mg/day () for the next 4 weeks.Results. The 75 mg group showed improvement in the total IPSS and QOL score in a dose-dependent manner (at 4 weeks: , at 4 weeks versus 8 weeks: ). In the 50 mg group, both scores reduced at 4 weeks, thereafter unchanged. The baseline slow stream score alone was higher in the 75 mg group (). The rate of change in the QOL score during the initial 4 weeks (ΔQOL) and Δnocturia was smaller in the 75 mg group ().Conclusions. Men with high slow stream score and unsatisfactory improvement in nocturia may benefit from dose escalation of naftopidil.


2013 ◽  
Vol 305 (9) ◽  
pp. F1265-F1276 ◽  
Author(s):  
Eric J. Gonzalez ◽  
Beatrice M. Girard ◽  
Margaret A. Vizzard

Numerous proinflammatory cytokines have been implicated in the reorganization of lower urinary tract function following cyclophosphamide (CYP)-induced cystitis. The present study investigated the functional profile of three pleiotropic transforming growth factor-β (TGF-β) isoforms and receptor (TβR) variants in the normal and inflamed (CYP-induced cystitis) rat urinary bladder. Our findings indicate that TGF-β (1, 2, and 3) and TβR (1, 2, and 3) transcript and protein expression were regulated to varying degrees in the urothelium or detrusor smooth muscle following intermediate (48 h; 150 mg/kg ip) or chronic (75 mg/kg ip; once every 3 days for 10 days), but not acute (4 h; 150 mg/kg ip), CYP-induced cystitis. Conscious, open-outlet cystometry was performed to determine whether aberrant TGF-β signaling contributes to urinary bladder dysfunction following intermediate (48 h) CYP-induced cystitis. TβR-1 inhibition with SB505124 (5 μM) significantly (p ≤ 0.001) decreased voiding frequency and increased bladder capacity (2.5-fold), void volume (2.6-fold), and intercontraction intervals (2.5-fold) in CYP-treated (48 h) rats. Taken together, these results provide evidence for 1) the involvement of TGF-β in lower urinary tract neuroplasticity following urinary bladder inflammation, 2) a functional role of TGF-β signaling in the afferent limb of the micturition reflex, and 3) urinary bladder TβR-1 as a viable target to reduce voiding frequency with cystitis.


2004 ◽  
Vol 100 (6) ◽  
pp. 1497-1503 ◽  
Author(s):  
Peter W. Kuipers ◽  
Ed T. Kamphuis ◽  
Ger E. van Venrooij ◽  
John P. van Roy ◽  
Traian I. Ionescu ◽  
...  

Background Intrathecal administration of opioids may cause lower urinary tract dysfunction. In this study, the authors compared the effects of morphine and sufentanil administered intrathecally in a randomized double-blind fashion (two doses each) on lower urinary tract function in healthy male volunteers. Methods Urodynamic evaluation was performed before and every hour after drug administration up to complete recovery of lower urinary tract function using pressure and flow measurements recorded from catheters in the bladder and rectum. Sense of urge and urinary flow rates were assessed every hour by filling the bladder with its cystometric capacity and asking the patient to void. Full recovery was defined as a residual volume of less than 10% of bladder capacity and a maximum flow rate within 10% of the initial value. Results Intrathecal administration of both opioids caused dose-dependent suppression of detrusor contractility and decreased sensation of urge. Mean times to recovery of normal lower urinary tract function were 5 and 8 h after 10 or 30 microg sufentanil and 14 and 20 h after 0.1 or 0.3 mg morphine, respectively. This recovery profile can be explained by the spinal pharmacokinetics of both opioids. Conclusions Intrathecal opioids decrease bladder function by causing dose-dependent suppression of detrusor contractility and decreased sensation of urge. Recovery of normal lower urinary tract function is significantly faster after intrathecal sufentanil than after morphine, and the recovery time is clearly dose dependent.


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