<b>Increased expression of 5-HT</b><b>_2A</b><b> and 5-HT</b><b>_2B</b><b> receptors in detrusor muscle after partial bladder outlet obstruction in </b><b>rats </b>

Abstract

Serotonin (5-hydroxytryptamine; 5-HT)-induced bladder contraction is enhanced after partial bladder outlet obstruction (pBOO) in rats. We investigated time-dependent changes in bladder contraction and expression of 5-HT 2A and 5-HT 2B receptor mRNA in bladder tissue to elucidate the mechanism of this enhancement. On day 3 and 7 after pBOO, contractile responses of isolated rat bladder strips to 5-HT were increased compared with that in sham-operated rats; on day 14, the response had decreased to the same level as that in sham rat bladders. In contrast, carbacholinduced contraction was not enhanced by pBOO at any time point. In sham rats, 5-HT 2A receptor mRNA was expressed in the urothelium, and 5-HT 2B receptor mRNA was expressed in the detrusor muscle layer. In pBOO rats, both receptor mRNAs were increased in the detrusor muscle and subserosal layers, but not in the urothelium. The increase of 5-HT 2A receptor mRNA was maintained from day 3 to day 14 after pBOO, and 5-HT 2B receptor mRNA was increased on day 7 after pBOO. These results suggested that pBOO induced up-regulation of the 5-HT 2A and 5-HT 2B receptors in the detrusor muscle and subserosal layers of the bladder, and such up-regulation may be related to the enhanced bladder contractile response to 5-HT.Partial bladder outlet obstruction (pBOO) secondary to benign prostate hyperplasia has been considered an important factor associated with lower urinary tract symptoms (LUTS). LUTS include voiding symptoms (e.g., weak urine stream and urinary retention) and storage symptoms (e.g., urinary frequency, urgency and nocturia) (1). Voiding symptom is attributed to increased urethral resistance due to static and dynamic prostatic obstruction. In contrast, the mechanism responsible for storage symptoms secondary to pBOO remains unknown. To clarify the mechanism, several changes in the bladder have been investigated with animal models of pBOO (13,14,17). In these animal models, urothelium, subserosal layer, and detrusor muscle layer of the bladder are thickened (2, 7, 24). These morphological alterations result in some functional changes, such as detrusor overactivity. These morphological and functional alterations reach different states at different time points after pBOO (2,16,19). Therefore, both morphological and functional changes must be evaluated at several time points to reveal the mechanisms responsible for the storage symptoms secondary to pBOO. One of the important functional changes in the bladder with pBOO is the contractile response associated with detrusor overactivity. Contractile responses to ATP and acetylcholine are changed by pBOO; however, descriptions of these changes are not consistent among reports (2,7,19,25). Therefore, the myogenic change caused by pBOO is not fully understood. Serotonin (5-hydroxytryptamine; 5-HT) is a mono-

Benefits and limitations of animal models in partial bladder outlet obstruction for translational research

“…A large number of studies focused on the compensated phase. The typical histological appearance of the wall of the pBOO bladder is bladder hypertrophy by wall thickness and a significant increase in bladder weight, which is similarly observed in patients with BPH . Electron microscopic studies have shown that muscle hypertrophy and hyperplasia increased collagen deposition and a loss of parasympathetic nerve terminals, which could result from unstable electrical status and might have spread disordered patterns of current .…”

Chronic spinal cord injury causes upregulation of serotonin (5‐HT)2A and 5‐HT2C receptors in lumbosacral cord motoneurons

“…Interestingly, we also noted that DOI improved the storage dysfunction, as shown by a reduction in NVCs in SCI. Previous studies have reported that 5‐HT 2A and 5‐HT 2C exist in the bladder of both humans and rats . Moreover, it has been reported that the 5‐HT2 receptor plays a major role in the effects of serotonin on the responses of the rat bladder contractions ; thus, we speculate that the effect of DOI on NVCs is exerted via its direct effect on the bladder, strengthening the contractile force of the bladder to promote effective voiding.…”

Long‐term administration of alpha‐1 blocker can reverse the micturition pattern in a bladder outlet obstruction murine model

“…This phenomenon might be related to the mechanism(s) whereby this compound relieves storage symptoms in BPH patients. A previous investigation reported that the expression of 5‐HT2A and 5‐HT2B receptors in the bladder is upregulated in the very early phase of pBOO in the rat model 24 . Khan et al.…”

“…A previous investigation reported that the expression of 5-HT2A and 5-HT2B receptors in the bladder is upregulated in the very early phase of pBOO in the rat model. 24 Khan et al used autoradiography to show a significant time-dependent upregulation of neuronal 5-HT binding sites in the detrusor muscle of rabbits subjected to pBOO. 25 Specifically, at 6 weeks after surgical induction of pBOO, samples of detrusor muscle showed an increase in the number of 5-HT binding sites, a change not seen in the early phase of pBOO, indicating the existence of a critical window for the effects of pBOO.…”