| First Author | Sadegh MK | Year | 2011 |
| Journal | Br J Pharmacol | Volume | 162 |
| Issue | 5 | Pages | 1156-70 |
| PubMed ID | 21091642 | Mgi Jnum | J:328804 |
| Mgi Id | MGI:7338876 | Doi | 10.1111/j.1476-5381.2010.01115.x |
| Citation | Sadegh MK, et al. (2011) Biomechanical properties and innervation of the female caveolin-1-deficient detrusor. Br J Pharmacol 162(5):1156-70 |
| abstractText | BACKGROUND AND PURPOSE: Caveolin-1-deficiency is associated with substantial urogenital alterations. Here, a mechanical, histological and biochemical characterization of female detrusors from wild-type and caveolin-1-deficient (KO) mice was made to increase the understanding of detrusor changes caused by lack of caveolae. EXPERIMENTAL APPROACH: Length-tension relationships were generated, and we recorded responses to electrical field stimulation, the muscarinic receptor agonist carbachol and the purinoceptor agonist ATP. Tyrosine nitration and the contents of caveolin-1, cavin-1, muscarinic M(3) receptors, phospholipase C(beta1), muscle-specific kinase (MuSK) and L-type Ca(2+) channels were determined by immunoblotting. Innervation was assessed by immunohistochemistry. KEY RESULTS: Bladder to body weight ratio was not changed, nor was there any change in the optimum circumference for force development. Depolarization- and ATP-induced stress was reduced, as was carbachol-induced stress between 0.1 and 3 microM, but the supramaximal relative (% K(+)) response to carbachol was increased, as was M(3) expression. The scopolamine-sensitive component of the electrical field stimulation response was impaired, and yet bladder nerves contained little caveolin-1. The density of cholinergic nerves was unchanged, whereas CART- and CGRP-positive nerves were reduced. Immunoblotting revealed loss of MuSK. CONCLUSIONS AND IMPLICATIONS: Ablation of caveolae in the female detrusor leads to generalized impairment of contractility, ruling out prostate hypertrophy as a contributing factor. Cholinergic neuroeffector transmission is impaired without conspicuous changes in the density of cholinergic nerves or morphology of their terminals, but correlating with reduced expression of MuSK. |
