Inhibition of the contractile response of the rat detrusor muscle by the β2-adrenoceptor agonist clenbuterol

1. The effect of calcium antagonists on the contractile response of human and rat isolated detrusor muscle in vitro was investigated. The effect of treatment with nimodipine on rat detrusor muscle in vivo was also examined. 2. Nimodipine 0.1 μmol/l, nifedipine 0.1 μmol/l, nifedipine 0.25 μmol/l and verapamil 1.5 μmol/l reduced the maximum contractile response of isolated human detrusor muscle to carbachol by 42%, 35%, 41% and 28% respectively (P < 0.01). Verapamil 0.1 μmol/l had no significant effect on contractile response. 3. Nimodipine 0.1 μmol/l reduced the maximum contractile response of isolated rat detrusor muscle in vitro to electrical field stimulation and carbachol by 53% and 84% respectively (P < 0.01). 4. Rats were pretreated with nimodipine for 8 days (5 mg day−1 kg−1) or with a single dose. Serum nimodipine concentrations were higher in rats treated for 8 days. In rats treated with nimodipine for 8 days there was no significant difference in detrusor contractile response compared with controls. However, after one dose of nimodipine the maximum contractile response was significantly reduced compared with controls (P < 0.05). 5. At the concentrations studied, nimodipine had a greater inhibitory effect on the contractile response of isolated human detrusor muscle. Nimodipine significantly reduced the contractile response of rat detrusor muscle in vitro and after a single dose in vivo, but had no significant effect after 8 days' treatment in vivo. It is possible that chronic oral treatment with nimodipine caused an up-regulation of 1,4-dihydropyridine-sensitive calcium channels, which may explain the lack of clinical effect of chronic treatment with calcium antagonists in patients with detrusor instability.

Download Full-text

Age-Related Changes in the Rat Detrusor Muscle: The Contractile Response to Inorganic Ions

The Journal of Urology ◽

10.1016/s0022-5347(17)37955-7 ◽

1991 ◽

Vol 146 (3) ◽

pp. 891-894 ◽

Cited By ~ 18

Author(s):

Masahiko Saito ◽

Atsuo Kondo ◽

Momokazu Gotoh ◽

Kumiko Kato

Keyword(s):

Contractile Response ◽

Inorganic Ions ◽

Detrusor Muscle ◽

Age Related ◽

Age Related Changes

Download Full-text

α1-Adrenoceptor-mediated phosphorylation of myosin in rat-tail arterial smooth muscle

Biochemical Journal ◽

10.1042/bj3270669 ◽

1997 ◽

Vol 327 (3) ◽

pp. 669-674 ◽

Cited By ~ 25

Author(s):

Mitsuo MITA ◽

P. Michael WALSH

Keyword(s):

Light Chain ◽

Time Course ◽

Myosin Light Chain ◽

Kinase Inhibitor ◽

Contractile Response ◽

Bathing Medium ◽

Adrenoceptor Agonist ◽

Phosphoamino Acid Analysis ◽

Phosphopeptide Mapping ◽

Rat Tail

The mechanism of α1-adrenoceptor-mediated contraction was investigated in helical strips of the rat-tail artery. Muscle strips with the endothelium removed contracted in response to the α1-adrenoceptor agonist cirazoline, with half-maximal contraction at 0.23 μM. The contractile response to a submaximal concentration of cirazoline (0.3 μM) was biphasic, with a rapid phasic component peaking at approx. 30 s, followed by sustained tonic contraction. Phosphorylation of the 20 kDa light chain of myosin (LC20) in response to 0.3 μM cirazoline was also biphasic and closely matched the time-course of contraction. Resting LC20 phosphorylation levels were 0.22±0.06 mol of Pi/mol of LC20 (n = 3) and reached a maximum of 0.58±0.08 mol of Pi/mol of LC20 (n = 3). Phosphopeptide mapping and phosphoamino acid analysis revealed that LC20 phosphorylation occurred exclusively at serine-19. The sustained phase of contraction was eliminated by removal of extracellular Ca2+ and the phasic response was eliminated by depletion of endogenous Ca2+ stores. Both phases of the contractile response were restored by re-addition of Ca2+ to the bathing medium. LC20 phosphorylation and both phases of the contractile response to 0.3 μM cirazoline were inhibited by the myosin light-chain kinase inhibitor ML-9 (30 μM). Resting LC20 phosphorylation, however, was unaffected by ML-9. Finally, both phasic and tonic responses to 0.3 μM cirazoline were partially inhibited by chloroethylclonidine (50 μM), suggesting the involvement of both α1A and α1B adrenoceptors in these contractile responses.

Download Full-text

TRPM8 agonists modulate contraction of the pig urinary bladder

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2012-0406 ◽

2013 ◽

Vol 91 (7) ◽

pp. 503-509 ◽

Cited By ~ 8

Author(s):

Bahareh Vahabi ◽

Brian A. Parsons ◽

Olena Doran ◽

Anthony Rhodes ◽

Sarah Dean ◽

...

Keyword(s):

Transient Receptor Potential ◽

Contractile Response ◽

Contractile Function ◽

Receptor Potential ◽

Detrusor Muscle ◽

Trpm8 Channel ◽

Normal Bladder ◽

Bladder Contraction ◽

Transient Receptor ◽

Bladder Physiology

The transient receptor potential melastin-8 (TRPM8) channel is activated by the “cooling” compounds menthol and icilin. Pathophysiologically, it is implicated in the overactive bladder and bladder cooling reflex, but the activity of TRPM8 in normal bladder physiology is poorly understood. We investigated the distribution of TRPM8 channels and the effect of TRPM8 agonists on the contractile function of pig bladder (n = 35) strips and whole bladders. The distribution of TRPM8 was examined by immunohistochemistry. The effect of vesical or intravascular menthol (0.1–0.3 mmol/L) or icilin (50 μmol/L) on carbachol-induced isolated whole bladder contractions was monitored by recording vesical pressure. Strips of denuded detrusor or mucosa were mounted in organ baths to study the effect of TRPM8 agonists on the contractile responses to 10 μmol/L carbachol. TRPM8-like immunoreactivity was detected on pig urothelium. Intravascular menthol (0.3 mmol/L) and icilin (50 μmol/L) significantly decreased the magnitude of carbachol-induced whole bladder contraction, whereas vesical administration significantly increased the response. In detrusor and mucosal strips, both menthol (0.3 mmol/L) and icilin (50 μmol/L) inhibited carbachol-induced contractions. We conclude that the TRPM8 channel is expressed on the urothelium of pig bladder. In the whole organ, exposure of the urothelium to menthol or icilin increases the contractile response to carbachol. Where detrusor muscle is exposed directly to these compounds, the contractile response to carbachol is reduced.

Download Full-text