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The actions of neurotensin in rat bladder detrusor contractility.

Dong X, Bai X, Zhao J, Wang L, Wang Q, Li L - Sci Rep (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.

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.

No MeSH data available.


Related in: MedlinePlus

The relationship between NTs and the cholinergic system in tension recording.Treatment with CCH (0.1 μM) can increase contractile amplitude (A,B, aP < 0.001), whereas NTs did not further increase the effects induced by CCH (bP = 0.072, one-way ANOVA, eight muscle strips). Therefore, upon pretreatment with atropine (1 μM), the spontaneous and NTs-induced contractions were drastically inhibited (C,D, cP < 0.001, dP < 0.001). However, NTs reversed the inhibition of contraction amplitudes induced by atropine (eP < 0.001). Similarly, NTs increased contraction amplitude after pretreatment with METH (1 μM) (E,F, fP < 0.001). METH did not significantly inhibit the amplitude of spontaneous contraction (gP = 0.094, one-way ANOVA). However, 4-DAMP inhibited the amplitude of spontaneous contraction (G,H, hP < 0.001), and NTs reversed the inhibition. (iP < 0.001, one-way ANOVA).
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f5: The relationship between NTs and the cholinergic system in tension recording.Treatment with CCH (0.1 μM) can increase contractile amplitude (A,B, aP < 0.001), whereas NTs did not further increase the effects induced by CCH (bP = 0.072, one-way ANOVA, eight muscle strips). Therefore, upon pretreatment with atropine (1 μM), the spontaneous and NTs-induced contractions were drastically inhibited (C,D, cP < 0.001, dP < 0.001). However, NTs reversed the inhibition of contraction amplitudes induced by atropine (eP < 0.001). Similarly, NTs increased contraction amplitude after pretreatment with METH (1 μM) (E,F, fP < 0.001). METH did not significantly inhibit the amplitude of spontaneous contraction (gP = 0.094, one-way ANOVA). However, 4-DAMP inhibited the amplitude of spontaneous contraction (G,H, hP < 0.001), and NTs reversed the inhibition. (iP < 0.001, one-way ANOVA).

Mentions: Given that NTs is involved in the regulation of bladder voiding, we tested the effect of NTs on detrusor strip contraction. Using isometric tension recordings, NTs was added to a bath to examine its effects on isolated detrusor strip contraction (Fig. 4A). The administration of vehicle Kreb’s solution had no influence on detrusor strip contraction, whereas treatment with NTs (1 μM) significantly increased the amplitude (32.02 ± 2.35 vs. 14.45 ± 2.53 g/g tissue, P < 0.001) and decreased the frequency (4.60 ± 0.81 vs. 5.18 ± 0.80 times/min, P < 0.01) of contraction (Fig. 4B). Concentration-response effects were also detected following the administration of a gradient concentration of NTs and levocabastine (10–11 M to 10–6 M) (Fig. 4C). Increasing the NTs concentration resulted in enhanced contractility of the muscle strips that was primarily manifested as increases in amplitude, but different concentrations of levocabastine had no effect on detrusor contraction (Fig. 4D). In an experiment examining the relationship between NTs and the cholinergic system, NTs increased the contraction amplitude after pretreatment with 0.1 μM carbachol (CCH), but with no significant differences (42.75 ± 3.41 vs. 41.85 ± 2.88 g/g tissue, P = 0.072) (Fig. 5B), When the detrusor strips werepretreated with atropine, 4-DAMP, and methoctramine (METH), the spontaneous phasic activities were inhibited to a different degree by atropine (2.32 ± 0.58 vs. 14.45 ± 2.53, P < 0.001) or 4-DAMP (8.64 ± 2.25 vs. 14.45 ± 2.53 g/g tissue, P < 0.001), but not by METH (13.92 ± 1.61 vs. 14.45 ± 2.53 g/g tissue, P = 0.094), NTs partially reversed the inhibition by atropine (7.84 ± 2.23 vs. 2.32 ± 0.58 g/g tissue, P < 0.001) or 4-DAMP (25.63 ± 3.85 vs. 8.64 ± 2.25 g/g tissue, P < 0.001), and increased the contraction amplitude after pretreating with METH (31.10 ± 3.51 vs. 13.92 ± 1.61 g/g tissue, P < 0.001, Fig. 5D,F,H).


The actions of neurotensin in rat bladder detrusor contractility.

Dong X, Bai X, Zhao J, Wang L, Wang Q, Li L - Sci Rep (2015)

The relationship between NTs and the cholinergic system in tension recording.Treatment with CCH (0.1 μM) can increase contractile amplitude (A,B, aP < 0.001), whereas NTs did not further increase the effects induced by CCH (bP = 0.072, one-way ANOVA, eight muscle strips). Therefore, upon pretreatment with atropine (1 μM), the spontaneous and NTs-induced contractions were drastically inhibited (C,D, cP < 0.001, dP < 0.001). However, NTs reversed the inhibition of contraction amplitudes induced by atropine (eP < 0.001). Similarly, NTs increased contraction amplitude after pretreatment with METH (1 μM) (E,F, fP < 0.001). METH did not significantly inhibit the amplitude of spontaneous contraction (gP = 0.094, one-way ANOVA). However, 4-DAMP inhibited the amplitude of spontaneous contraction (G,H, hP < 0.001), and NTs reversed the inhibition. (iP < 0.001, one-way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4459202&req=5

f5: The relationship between NTs and the cholinergic system in tension recording.Treatment with CCH (0.1 μM) can increase contractile amplitude (A,B, aP < 0.001), whereas NTs did not further increase the effects induced by CCH (bP = 0.072, one-way ANOVA, eight muscle strips). Therefore, upon pretreatment with atropine (1 μM), the spontaneous and NTs-induced contractions were drastically inhibited (C,D, cP < 0.001, dP < 0.001). However, NTs reversed the inhibition of contraction amplitudes induced by atropine (eP < 0.001). Similarly, NTs increased contraction amplitude after pretreatment with METH (1 μM) (E,F, fP < 0.001). METH did not significantly inhibit the amplitude of spontaneous contraction (gP = 0.094, one-way ANOVA). However, 4-DAMP inhibited the amplitude of spontaneous contraction (G,H, hP < 0.001), and NTs reversed the inhibition. (iP < 0.001, one-way ANOVA).
Mentions: Given that NTs is involved in the regulation of bladder voiding, we tested the effect of NTs on detrusor strip contraction. Using isometric tension recordings, NTs was added to a bath to examine its effects on isolated detrusor strip contraction (Fig. 4A). The administration of vehicle Kreb’s solution had no influence on detrusor strip contraction, whereas treatment with NTs (1 μM) significantly increased the amplitude (32.02 ± 2.35 vs. 14.45 ± 2.53 g/g tissue, P < 0.001) and decreased the frequency (4.60 ± 0.81 vs. 5.18 ± 0.80 times/min, P < 0.01) of contraction (Fig. 4B). Concentration-response effects were also detected following the administration of a gradient concentration of NTs and levocabastine (10–11 M to 10–6 M) (Fig. 4C). Increasing the NTs concentration resulted in enhanced contractility of the muscle strips that was primarily manifested as increases in amplitude, but different concentrations of levocabastine had no effect on detrusor contraction (Fig. 4D). In an experiment examining the relationship between NTs and the cholinergic system, NTs increased the contraction amplitude after pretreatment with 0.1 μM carbachol (CCH), but with no significant differences (42.75 ± 3.41 vs. 41.85 ± 2.88 g/g tissue, P = 0.072) (Fig. 5B), When the detrusor strips werepretreated with atropine, 4-DAMP, and methoctramine (METH), the spontaneous phasic activities were inhibited to a different degree by atropine (2.32 ± 0.58 vs. 14.45 ± 2.53, P < 0.001) or 4-DAMP (8.64 ± 2.25 vs. 14.45 ± 2.53 g/g tissue, P < 0.001), but not by METH (13.92 ± 1.61 vs. 14.45 ± 2.53 g/g tissue, P = 0.094), NTs partially reversed the inhibition by atropine (7.84 ± 2.23 vs. 2.32 ± 0.58 g/g tissue, P < 0.001) or 4-DAMP (25.63 ± 3.85 vs. 8.64 ± 2.25 g/g tissue, P < 0.001), and increased the contraction amplitude after pretreating with METH (31.10 ± 3.51 vs. 13.92 ± 1.61 g/g tissue, P < 0.001, Fig. 5D,F,H).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.

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.

No MeSH data available.


Related in: MedlinePlus