Abstract
This study assessed the expression, distribution and function of neurotensin (NTs) and two main neurotensin receptors (NTSR), NTSR1 and NTSR2 in normal rat urinary bladders. NTs is primarily located in the suburothelium and the interstitium of smooth muscle bundles. The NTSR1 and NTSR2 receptor subtypes are found to co-localize with smooth muscle cells (SMCs). NTs not only can directly act on bladder SMCs to induce intracellular calcium mobilization by activating the phospholipase C/inositol triphosphate (PLC/IP3) pathway, promoting extracellular calcium influx through a non-selective cation channels, but may be also involved in the modulation of the cholinergic system. Nowadays, the selective antimuscarinic drugs (solifenacin) and the selective beta 3-adrenergic agonist (mirabegron) are used as the first-line pharmacotherapy for overactive bladder (OAB), but without satisfactory treatment benefits in some patients. This study provided evidence suggesting that bladder NTs may play an important role in the regulation of micturition. Further research is needed to investigate the effects of NTs on bladder contractility and the underlying mechanism, which might reveal that the administration of NTSR antagonists can potentially relieve the symptoms of OAB by coordination with antimuscarinic pharmacotherapy.
Highlights
NTs has been the focus of many original studies on physiological function and peripheral regulation
The reverse transcription-polymerase chain reaction results indicated that the mRNA of NTs (260 bp) and the two primary neurotensin receptors, NTSR1 (253 bp) and NTSR2 (198 bp), exist in rat bladders (Fig. 1A)
We observed that immunoreactive stained NTs are mostly present in the suburothelium region and partially distributed among smooth muscle bundles, but it is not clear whether NTs colocalize with nerve bundles, myofibroblast cells or interstitial cells, whereas NTSR1 and NTSR2 immunoreactive staining mainly occurs in the smooth muscle layer and urothelium compared with the negative control
Summary
NTs has been the focus of many original studies on physiological function and peripheral regulation. New ideas and evidences have emerged regarding the role of NTs in the contraction and pacemaker currents of the small intestine. The relationship between NTs and cholinergic systems has been documented in several research articles. There are no studies of NTs in the urinary bladder, and its possible role and mechanism are unclear. Several pharmacological agents were applied in functional measurements to ascertain the influences of NTs on the bladder detrusor and cholinergic systems. These results provide the first evidence that NTs may play an important role in the modulation of bladder detrusor contractility
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